Sample records for accelerated sequence evolution

  1. Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome

    PubMed Central

    Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

    2016-01-01

    Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. PMID:27401230

  2. Genome-Wide Identification of Regulatory Sequences Undergoing Accelerated Evolution in the Human Genome.

    PubMed

    Dong, Xinran; Wang, Xiao; Zhang, Feng; Tian, Weidong

    2016-10-01

    Accelerated evolution of regulatory sequence can alter the expression pattern of target genes, and cause phenotypic changes. In this study, we used DNase I hypersensitive sites (DHSs) to annotate putative regulatory sequences in the human genome, and conducted a genome-wide analysis of the effects of accelerated evolution on regulatory sequences. Working under the assumption that local ancient repeat elements of DHSs are under neutral evolution, we discovered that ∼0.44% of DHSs are under accelerated evolution (ace-DHSs). We found that ace-DHSs tend to be more active than background DHSs, and are strongly associated with epigenetic marks of active transcription. The target genes of ace-DHSs are significantly enriched in neuron-related functions, and their expression levels are positively selected in the human brain. Thus, these lines of evidences strongly suggest that accelerated evolution on regulatory sequences plays important role in the evolution of human-specific phenotypes. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. Insights into hominid evolution from the gorilla genome sequence

    PubMed Central

    Scally, Aylwyn; Dutheil, Julien Y.; Hillier, LaDeana W.; Jordan, Greg E.; Goodhead, Ian; Herrero, Javier; Hobolth, Asger; Lappalainen, Tuuli; Mailund, Thomas; Marques-Bonet, Tomas; McCarthy, Shane; Montgomery, Stephen H.; Schwalie, Petra C.; Tang, Y. Amy; Ward, Michelle C.; Xue, Yali; Yngvadottir, Bryndis; Alkan, Can; Andersen, Lars N.; Ayub, Qasim; Ball, Edward V.; Beal, Kathryn; Bradley, Brenda J.; Chen, Yuan; Clee, Chris M.; Fitzgerald, Stephen; Graves, Tina A.; Gu, Yong; Heath, Paul; Heger, Andreas; Karakoc, Emre; Kolb-Kokocinski, Anja; Laird, Gavin K.; Lunter, Gerton; Meader, Stephen; Mort, Matthew; Mullikin, James C.; Munch, Kasper; O’Connor, Timothy D.; Phillips, Andrew D.; Prado-Martinez, Javier; Rogers, Anthony S.; Sajjadian, Saba; Schmidt, Dominic; Shaw, Katy; Simpson, Jared T.; Stenson, Peter D.; Turner, Daniel J.; Vigilant, Linda; Vilella, Albert J.; Whitener, Weldon; Zhu, Baoli; Cooper, David N.; de Jong, Pieter; Dermitzakis, Emmanouil T.; Eichler, Evan E.; Flicek, Paul; Goldman, Nick; Mundy, Nicholas I.; Ning, Zemin; Odom, Duncan T.; Ponting, Chris P.; Quail, Michael A.; Ryder, Oliver A.; Searle, Stephen M.; Warren, Wesley C.; Wilson, Richard K.; Schierup, Mikkel H.; Rogers, Jane; Tyler-Smith, Chris; Durbin, Richard

    2012-01-01

    Summary Gorillas are humans’ closest living relatives after chimpanzees, and are of comparable importance for the study of human origins and evolution. Here we present the assembly and analysis of a genome sequence for the western lowland gorilla, and compare the whole genomes of all extant great ape genera. We propose a synthesis of genetic and fossil evidence consistent with placing the human-chimpanzee and human-chimpanzee-gorilla speciation events at approximately 6 and 10 million years ago (Mya). In 30% of the genome, gorilla is closer to human or chimpanzee than the latter are to each other; this is rarer around coding genes, indicating pervasive selection throughout great ape evolution, and has functional consequences in gene expression. A comparison of protein coding genes reveals approximately 500 genes showing accelerated evolution on each of the gorilla, human and chimpanzee lineages, and evidence for parallel acceleration, particularly of genes involved in hearing. We also compare the western and eastern gorilla species, estimating an average sequence divergence time 1.75 million years ago, but with evidence for more recent genetic exchange and a population bottleneck in the eastern species. The use of the genome sequence in these and future analyses will promote a deeper understanding of great ape biology and evolution. PMID:22398555

  4. ACCELERATED EVOLUTION OF LAND SNAILS MANDARINA IN THE OCEANIC BONIN ISLANDS: EVIDENCE FROM MITOCHONDRIAL DNA SEQUENCES.

    PubMed

    Chiba, Satoshi

    1999-04-01

    An endemic land snail genus Mandarina of the oceanic Bonin (Ogasawara) Islands shows exceptionally rapid evolution not only of morphological and ecological traits, but of DNA sequence. A phylogenetic relationship based on mitochondrial DNA (mtDNA) sequences suggests that morphological differences equivalent to the differences between families were produced between Mandarina and its ancestor during the Pleistocene. The inferred phylogeny shows that species with similar morphologies and life habitats appeared repeatedly and independently in different lineages and islands at different times. Sequential adaptive radiations occurred in different islands of the Bonin Islands and species occupying arboreal, semiarboreal, and terrestrial habitat arose independently in each island. Because of a close relationship between shell morphology and life habitat, independent evolution of the same life habitat in different islands created species possesing the same shell morphology in different islands and lineages. This rapid evolution produced some incongruences between phylogenetic relationship and species taxonomy. Levels of sequence divergence of mtDNA among the species of Mandarina is extremely high. The maximum level of sequence divergence at 16S and 12S ribosomal RNA sequence within Mandarina are 18.7% and 17.7%, respectively, and this suggests that evolution of mtDNA of Mandarina is extremely rapid, more than 20 times faster than the standard rate in other animals. The present examination reveals that evolution of morphological and ecological traits occurs at extremely high rates in the time of adaptive radiation, especially in fragmented environments. © 1999 The Society for the Study of Evolution.

  5. Implications of the plastid genome sequence of typha (typhaceae, poales) for understanding genome evolution in poaceae.

    PubMed

    Guisinger, Mary M; Chumley, Timothy W; Kuehl, Jennifer V; Boore, Jeffrey L; Jansen, Robert K

    2010-02-01

    Plastid genomes of the grasses (Poaceae) are unusual in their organization and rates of sequence evolution. There has been a recent surge in the availability of grass plastid genome sequences, but a comprehensive comparative analysis of genome evolution has not been performed that includes any related families in the Poales. We report on the plastid genome of Typha latifolia, the first non-grass Poales sequenced to date, and we present comparisons of genome organization and sequence evolution within Poales. Our results confirm that grass plastid genomes exhibit acceleration in both genomic rearrangements and nucleotide substitutions. Poaceae have multiple structural rearrangements, including three inversions, three genes losses (accD, ycf1, ycf2), intron losses in two genes (clpP, rpoC1), and expansion of the inverted repeat (IR) into both large and small single-copy regions. These rearrangements are restricted to the Poaceae, and IR expansion into the small single-copy region correlates with the phylogeny of the family. Comparisons of 73 protein-coding genes for 47 angiosperms including nine Poaceae genera confirm that the branch leading to Poaceae has significantly accelerated rates of change relative to other monocots and angiosperms. Furthermore, rates of sequence evolution within grasses are lower, indicating a deceleration during diversification of the family. Overall there is a strong correlation between accelerated rates of genomic rearrangements and nucleotide substitutions in Poaceae, a phenomenon that has been noted recently throughout angiosperms. The cause of the correlation is unknown, but faulty DNA repair has been suggested in other systems including bacterial and animal mitochondrial genomes.

  6. Mimosoid legume plastome evolution: IR expansion, tandem repeat expansions, and accelerated rate of evolution in clpP.

    PubMed

    Dugas, Diana V; Hernandez, David; Koenen, Erik J M; Schwarz, Erika; Straub, Shannon; Hughes, Colin E; Jansen, Robert K; Nageswara-Rao, Madhugiri; Staats, Martijn; Trujillo, Joshua T; Hajrah, Nahid H; Alharbi, Njud S; Al-Malki, Abdulrahman L; Sabir, Jamal S M; Bailey, C Donovan

    2015-11-23

    The Leguminosae has emerged as a model for studying angiosperm plastome evolution because of its striking diversity of structural rearrangements and sequence variation. However, most of what is known about legume plastomes comes from few genera representing a subset of lineages in subfamily Papilionoideae. We investigate plastome evolution in subfamily Mimosoideae based on two newly sequenced plastomes (Inga and Leucaena) and two recently published plastomes (Acacia and Prosopis), and discuss the results in the context of other legume and rosid plastid genomes. Mimosoid plastomes have a typical angiosperm gene content and general organization as well as a generally slow rate of protein coding gene evolution, but they are the largest known among legumes. The increased length results from tandem repeat expansions and an unusual 13 kb IR-SSC boundary shift in Acacia and Inga. Mimosoid plastomes harbor additional interesting features, including loss of clpP intron1 in Inga, accelerated rates of evolution in clpP for Acacia and Inga, and dN/dS ratios consistent with neutral and positive selection for several genes. These new plastomes and results provide important resources for legume comparative genomics, plant breeding, and plastid genetic engineering, while shedding further light on the complexity of plastome evolution in legumes and angiosperms.

  7. Accelerated Evolution of the ASPM Gene Controlling Brain Size Begins Prior to Human Brain Expansion

    PubMed Central

    Solomon, Gregory; Gersch, William; Yoon, Young-Ho; Collura, Randall; Ruvolo, Maryellen; Barrett, J. Carl; Woods, C. Geoffrey; Walsh, Christopher A

    2004-01-01

    Primary microcephaly (MCPH) is a neurodevelopmental disorder characterized by global reduction in cerebral cortical volume. The microcephalic brain has a volume comparable to that of early hominids, raising the possibility that some MCPH genes may have been evolutionary targets in the expansion of the cerebral cortex in mammals and especially primates. Mutations in ASPM, which encodes the human homologue of a fly protein essential for spindle function, are the most common known cause of MCPH. Here we have isolated large genomic clones containing the complete ASPM gene, including promoter regions and introns, from chimpanzee, gorilla, orangutan, and rhesus macaque by transformation-associated recombination cloning in yeast. We have sequenced these clones and show that whereas much of the sequence of ASPM is substantially conserved among primates, specific segments are subject to high Ka/Ks ratios (nonsynonymous/synonymous DNA changes) consistent with strong positive selection for evolutionary change. The ASPM gene sequence shows accelerated evolution in the African hominoid clade, and this precedes hominid brain expansion by several million years. Gorilla and human lineages show particularly accelerated evolution in the IQ domain of ASPM. Moreover, ASPM regions under positive selection in primates are also the most highly diverged regions between primates and nonprimate mammals. We report the first direct application of TAR cloning technology to the study of human evolution. Our data suggest that evolutionary selection of specific segments of the ASPM sequence strongly relates to differences in cerebral cortical size. PMID:15045028

  8. Mercury BLASTP: Accelerating Protein Sequence Alignment

    PubMed Central

    Jacob, Arpith; Lancaster, Joseph; Buhler, Jeremy; Harris, Brandon; Chamberlain, Roger D.

    2008-01-01

    Large-scale protein sequence comparison is an important but compute-intensive task in molecular biology. BLASTP is the most popular tool for comparative analysis of protein sequences. In recent years, an exponential increase in the size of protein sequence databases has required either exponentially more running time or a cluster of machines to keep pace. To address this problem, we have designed and built a high-performance FPGA-accelerated version of BLASTP, Mercury BLASTP. In this paper, we describe the architecture of the portions of the application that are accelerated in the FPGA, and we also describe the integration of these FPGA-accelerated portions with the existing BLASTP software. We have implemented Mercury BLASTP on a commodity workstation with two Xilinx Virtex-II 6000 FPGAs. We show that the new design runs 11-15 times faster than software BLASTP on a modern CPU while delivering close to 99% identical results. PMID:19492068

  9. Mutational Pathway Determines Whether Drug Gradients Accelerate Evolution of Drug-Resistant Cells

    NASA Astrophysics Data System (ADS)

    Greulich, Philip; Waclaw, Bartłomiej; Allen, Rosalind J.

    2012-08-01

    Drug gradients are believed to play an important role in the evolution of bacteria resistant to antibiotics and tumors resistant to anticancer drugs. We use a statistical physics model to study the evolution of a population of malignant cells exposed to drug gradients, where drug resistance emerges via a mutational pathway involving multiple mutations. We show that a nonuniform drug distribution has the potential to accelerate the emergence of resistance when the mutational pathway involves a long sequence of mutants with increasing resistance, but if the pathway is short or crosses a fitness valley, the evolution of resistance may actually be slowed down by drug gradients. These predictions can be verified experimentally, and may help to improve strategies for combating the emergence of resistance.

  10. The genome sequence of taurine cattle: a window to ruminant biology and evolution.

    PubMed

    Elsik, Christine G; Tellam, Ross L; Worley, Kim C; Gibbs, Richard A; Muzny, Donna M; Weinstock, George M; Adelson, David L; Eichler, Evan E; Elnitski, Laura; Guigó, Roderic; Hamernik, Debora L; Kappes, Steve M; Lewin, Harris A; Lynn, David J; Nicholas, Frank W; Reymond, Alexandre; Rijnkels, Monique; Skow, Loren C; Zdobnov, Evgeny M; Schook, Lawrence; Womack, James; Alioto, Tyler; Antonarakis, Stylianos E; Astashyn, Alex; Chapple, Charles E; Chen, Hsiu-Chuan; Chrast, Jacqueline; Câmara, Francisco; Ermolaeva, Olga; Henrichsen, Charlotte N; Hlavina, Wratko; Kapustin, Yuri; Kiryutin, Boris; Kitts, Paul; Kokocinski, Felix; Landrum, Melissa; Maglott, Donna; Pruitt, Kim; Sapojnikov, Victor; Searle, Stephen M; Solovyev, Victor; Souvorov, Alexandre; Ucla, Catherine; Wyss, Carine; Anzola, Juan M; Gerlach, Daniel; Elhaik, Eran; Graur, Dan; Reese, Justin T; Edgar, Robert C; McEwan, John C; Payne, Gemma M; Raison, Joy M; Junier, Thomas; Kriventseva, Evgenia V; Eyras, Eduardo; Plass, Mireya; Donthu, Ravikiran; Larkin, Denis M; Reecy, James; Yang, Mary Q; Chen, Lin; Cheng, Ze; Chitko-McKown, Carol G; Liu, George E; Matukumalli, Lakshmi K; Song, Jiuzhou; Zhu, Bin; Bradley, Daniel G; Brinkman, Fiona S L; Lau, Lilian P L; Whiteside, Matthew D; Walker, Angela; Wheeler, Thomas T; Casey, Theresa; German, J Bruce; Lemay, Danielle G; Maqbool, Nauman J; Molenaar, Adrian J; Seo, Seongwon; Stothard, Paul; Baldwin, Cynthia L; Baxter, Rebecca; Brinkmeyer-Langford, Candice L; Brown, Wendy C; Childers, Christopher P; Connelley, Timothy; Ellis, Shirley A; Fritz, Krista; Glass, Elizabeth J; Herzig, Carolyn T A; Iivanainen, Antti; Lahmers, Kevin K; Bennett, Anna K; Dickens, C Michael; Gilbert, James G R; Hagen, Darren E; Salih, Hanni; Aerts, Jan; Caetano, Alexandre R; Dalrymple, Brian; Garcia, Jose Fernando; Gill, Clare A; Hiendleder, Stefan G; Memili, Erdogan; Spurlock, Diane; Williams, John L; Alexander, Lee; Brownstein, Michael J; Guan, Leluo; Holt, Robert A; Jones, Steven J M; Marra, Marco A; Moore, Richard; Moore, Stephen S; Roberts, Andy; Taniguchi, Masaaki; Waterman, Richard C; Chacko, Joseph; Chandrabose, Mimi M; Cree, Andy; Dao, Marvin Diep; Dinh, Huyen H; Gabisi, Ramatu Ayiesha; Hines, Sandra; Hume, Jennifer; Jhangiani, Shalini N; Joshi, Vandita; Kovar, Christie L; Lewis, Lora R; Liu, Yih-Shin; Lopez, John; Morgan, Margaret B; Nguyen, Ngoc Bich; Okwuonu, Geoffrey O; Ruiz, San Juana; Santibanez, Jireh; Wright, Rita A; Buhay, Christian; Ding, Yan; Dugan-Rocha, Shannon; Herdandez, Judith; Holder, Michael; Sabo, Aniko; Egan, Amy; Goodell, Jason; Wilczek-Boney, Katarzyna; Fowler, Gerald R; Hitchens, Matthew Edward; Lozado, Ryan J; Moen, Charles; Steffen, David; Warren, James T; Zhang, Jingkun; Chiu, Readman; Schein, Jacqueline E; Durbin, K James; Havlak, Paul; Jiang, Huaiyang; Liu, Yue; Qin, Xiang; Ren, Yanru; Shen, Yufeng; Song, Henry; Bell, Stephanie Nicole; Davis, Clay; Johnson, Angela Jolivet; Lee, Sandra; Nazareth, Lynne V; Patel, Bella Mayurkumar; Pu, Ling-Ling; Vattathil, Selina; Williams, Rex Lee; Curry, Stacey; Hamilton, Cerissa; Sodergren, Erica; Wheeler, David A; Barris, Wes; Bennett, Gary L; Eggen, André; Green, Ronnie D; Harhay, Gregory P; Hobbs, Matthew; Jann, Oliver; Keele, John W; Kent, Matthew P; Lien, Sigbjørn; McKay, Stephanie D; McWilliam, Sean; Ratnakumar, Abhirami; Schnabel, Robert D; Smith, Timothy; Snelling, Warren M; Sonstegard, Tad S; Stone, Roger T; Sugimoto, Yoshikazu; Takasuga, Akiko; Taylor, Jeremy F; Van Tassell, Curtis P; Macneil, Michael D; Abatepaulo, Antonio R R; Abbey, Colette A; Ahola, Virpi; Almeida, Iassudara G; Amadio, Ariel F; Anatriello, Elen; Bahadue, Suria M; Biase, Fernando H; Boldt, Clayton R; Carroll, Jeffery A; Carvalho, Wanessa A; Cervelatti, Eliane P; Chacko, Elsa; Chapin, Jennifer E; Cheng, Ye; Choi, Jungwoo; Colley, Adam J; de Campos, Tatiana A; De Donato, Marcos; Santos, Isabel K F de Miranda; de Oliveira, Carlo J F; Deobald, Heather; Devinoy, Eve; Donohue, Kaitlin E; Dovc, Peter; Eberlein, Annett; Fitzsimmons, Carolyn J; Franzin, Alessandra M; Garcia, Gustavo R; Genini, Sem; Gladney, Cody J; Grant, Jason R; Greaser, Marion L; Green, Jonathan A; Hadsell, Darryl L; Hakimov, Hatam A; Halgren, Rob; Harrow, Jennifer L; Hart, Elizabeth A; Hastings, Nicola; Hernandez, Marta; Hu, Zhi-Liang; Ingham, Aaron; Iso-Touru, Terhi; Jamis, Catherine; Jensen, Kirsty; Kapetis, Dimos; Kerr, Tovah; Khalil, Sari S; Khatib, Hasan; Kolbehdari, Davood; Kumar, Charu G; Kumar, Dinesh; Leach, Richard; Lee, Justin C-M; Li, Changxi; Logan, Krystin M; Malinverni, Roberto; Marques, Elisa; Martin, William F; Martins, Natalia F; Maruyama, Sandra R; Mazza, Raffaele; McLean, Kim L; Medrano, Juan F; Moreno, Barbara T; Moré, Daniela D; Muntean, Carl T; Nandakumar, Hari P; Nogueira, Marcelo F G; Olsaker, Ingrid; Pant, Sameer D; Panzitta, Francesca; Pastor, Rosemeire C P; Poli, Mario A; Poslusny, Nathan; Rachagani, Satyanarayana; Ranganathan, Shoba; Razpet, Andrej; Riggs, Penny K; Rincon, Gonzalo; Rodriguez-Osorio, Nelida; Rodriguez-Zas, Sandra L; Romero, Natasha E; Rosenwald, Anne; Sando, Lillian; Schmutz, Sheila M; Shen, Libing; Sherman, Laura; Southey, Bruce R; Lutzow, Ylva Strandberg; Sweedler, Jonathan V; Tammen, Imke; Telugu, Bhanu Prakash V L; Urbanski, Jennifer M; Utsunomiya, Yuri T; Verschoor, Chris P; Waardenberg, Ashley J; Wang, Zhiquan; Ward, Robert; Weikard, Rosemarie; Welsh, Thomas H; White, Stephen N; Wilming, Laurens G; Wunderlich, Kris R; Yang, Jianqi; Zhao, Feng-Qi

    2009-04-24

    To understand the biology and evolution of ruminants, the cattle genome was sequenced to about sevenfold coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1217 are absent or undetected in noneutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides a resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production.

  11. Accelerated Evolution of the Pituitary Adenylate Cyclase-Activating Polypeptide Precursor Gene During Human Origin

    PubMed Central

    Wang, Yin-qiu; Qian, Ya-ping; Yang, Su; Shi, Hong; Liao, Cheng-hong; Zheng, Hong-Kun; Wang, Jun; Lin, Alice A.; Cavalli-Sforza, L. Luca; Underhill, Peter A.; Chakraborty, Ranajit; Jin, Li; Su, Bing

    2005-01-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than that in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors, which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition. PMID:15834139

  12. The Genome Sequence of Taurine Cattle: A window to ruminant biology and evolution

    PubMed Central

    Elsik, Christine G.; Tellam, Ross L.; Worley, Kim C.

    2010-01-01

    To understand the biology and evolution of ruminants, the cattle genome was sequenced to ∼7× coverage. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs shared among seven mammalian species of which 1,217 are absent or undetected in non-eutherian (marsupial or monotreme) genomes. Cattle-specific evolutionary breakpoint regions in chromosomes have a higher density of segmental duplications, enrichment of repetitive elements, and species-specific variations in genes associated with lactation and immune responsiveness. Genes involved in metabolism are generally highly conserved, although five metabolic genes are deleted or extensively diverged from their human orthologs. The cattle genome sequence thus provides an enabling resource for understanding mammalian evolution and accelerating livestock genetic improvement for milk and meat production. PMID:19390049

  13. Acceleration of convergence of vector sequences

    NASA Technical Reports Server (NTRS)

    Sidi, A.; Ford, W. F.; Smith, D. A.

    1983-01-01

    A general approach to the construction of convergence acceleration methods for vector sequence is proposed. Using this approach, one can generate some known methods, such as the minimal polynomial extrapolation, the reduced rank extrapolation, and the topological epsilon algorithm, and also some new ones. Some of the new methods are easier to implement than the known methods and are observed to have similar numerical properties. The convergence analysis of these new methods is carried out, and it is shown that they are especially suitable for accelerating the convergence of vector sequences that are obtained when one solves linear systems of equations iteratively. A stability analysis is also given, and numerical examples are provided. The convergence and stability properties of the topological epsilon algorithm are likewise given.

  14. Molecular evolution and diversification of snake toxin genes, revealed by analysis of intron sequences.

    PubMed

    Fujimi, T J; Nakajyo, T; Nishimura, E; Ogura, E; Tsuchiya, T; Tamiya, T

    2003-08-14

    The genes encoding erabutoxin (short chain neurotoxin) isoforms (Ea, Eb, and Ec), LsIII (long chain neurotoxin) and a novel long chain neurotoxin pseudogene were cloned from a Laticauda semifasciata genomic library. Short and long chain neurotoxin genes were also cloned from the genome of Laticauda laticaudata, a closely related species of L. semifasciata, by PCR. A putative matrix attached region (MAR) sequence was found in the intron I of the LsIII gene. Comparative analysis of 11 structurally relevant snake toxin genes (three-finger-structure toxins) revealed the molecular evolution of these toxins. Three-finger-structure toxin genes diverged from a common ancestor through two types of evolutionary pathways (long and short types), early in the course of evolution. At a later stage of evolution in each gene, the accumulation of mutations in the exons, especially exon II, by accelerated evolution may have caused the increased diversification in their functions. It was also revealed that the putative MAR sequence found in the LsIII gene was integrated into the gene after the species-level divergence.

  15. Rotational evolution of slow-rotator sequence stars

    NASA Astrophysics Data System (ADS)

    Lanzafame, A. C.; Spada, F.

    2015-12-01

    Context. The observed relationship between mass, age and rotation in open clusters shows the progressive development of a slow-rotator sequence among stars possessing a radiative interior and a convective envelope during their pre-main sequence and main-sequence evolution. After 0.6 Gyr, most cluster members of this type have settled on this sequence. Aims: The observed clustering on this sequence suggests that it corresponds to some equilibrium or asymptotic condition that still lacks a complete theoretical interpretation, and which is crucial to our understanding of the stellar angular momentum evolution. Methods: We couple a rotational evolution model, which takes internal differential rotation into account, with classical and new proposals for the wind braking law, and fit models to the data using a Monte Carlo Markov chain (MCMC) method tailored to the problem at hand. We explore to what extent these models are able to reproduce the mass and time dependence of the stellar rotational evolution on the slow-rotator sequence. Results: The description of the evolution of the slow-rotator sequence requires taking the transfer of angular momentum from the radiative core to the convective envelope into account. We find that, in the mass range 0.85-1.10 M⊙, the core-envelope coupling timescale for stars in the slow-rotator sequence scales as M-7.28. Quasi-solid body rotation is achieved only after 1-2 Gyr, depending on stellar mass, which implies that observing small deviations from the Skumanich law (P ∝ √{t}) would require period data of older open clusters than is available to date. The observed evolution in the 0.1-2.5 Gyr age range and in the 0.85-1.10 M⊙ mass range is best reproduced by assuming an empirical mass dependence of the wind angular momentum loss proportional to the convective turnover timescale and to the stellar moment of inertia. Period isochrones based on our MCMC fit provide a tool for inferring stellar ages of solar-like main-sequence

  16. Extinction events can accelerate evolution.

    PubMed

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term.

  17. Extinction Events Can Accelerate Evolution

    PubMed Central

    Lehman, Joel; Miikkulainen, Risto

    2015-01-01

    Extinction events impact the trajectory of biological evolution significantly. They are often viewed as upheavals to the evolutionary process. In contrast, this paper supports the hypothesis that although they are unpredictably destructive, extinction events may in the long term accelerate evolution by increasing evolvability. In particular, if extinction events extinguish indiscriminately many ways of life, indirectly they may select for the ability to expand rapidly through vacated niches. Lineages with such an ability are more likely to persist through multiple extinctions. Lending computational support for this hypothesis, this paper shows how increased evolvability will result from simulated extinction events in two computational models of evolved behavior. The conclusion is that although they are destructive in the short term, extinction events may make evolution more prolific in the long term. PMID:26266804

  18. DNA and RNA editing of retrotransposons accelerate mammalian genome evolution.

    PubMed

    Knisbacher, Binyamin A; Levanon, Erez Y

    2015-04-01

    Genome evolution is commonly viewed as a gradual process that is driven by random mutations that accumulate over time. However, DNA- and RNA-editing enzymes have been identified that can accelerate evolution by actively modifying the genomically encoded information. The apolipoprotein B mRNA editing enzymes, catalytic polypeptide-like (APOBECs) are potent restriction factors that can inhibit retroelements by cytosine-to-uridine editing of retroelement DNA after reverse transcription. In some cases, a retroelement may successfully integrate into the genome despite being hypermutated. Such events introduce unique sequences into the genome and are thus a source of genomic innovation. adenosine deaminases that act on RNA (ADARs) catalyze adenosine-to-inosine editing in double-stranded RNA, commonly formed by oppositely oriented retroelements. The RNA editing confers plasticity to the transcriptome by generating many transcript variants from a single genomic locus. If the editing produces a beneficial variant, the genome may maintain the locus that produces the RNA-edited transcript for its novel function. Here, we discuss how these two powerful editing mechanisms, which both target inserted retroelements, facilitate expedited genome evolution. © 2015 New York Academy of Sciences.

  19. Sequence-Level Mechanisms of Human Epigenome Evolution

    PubMed Central

    Prendergast, James G.D.; Chambers, Emily V.; Semple, Colin A.M.

    2014-01-01

    DNA methylation and chromatin states play key roles in development and disease. However, the extent of recent evolutionary divergence in the human epigenome and the influential factors that have shaped it are poorly understood. To determine the links between genome sequence and human epigenome evolution, we examined the divergence of DNA methylation and chromatin states following segmental duplication events in the human lineage. Chromatin and DNA methylation states were found to have been generally well conserved following a duplication event, with the evolution of the epigenome largely uncoupled from the total number of genetic changes in the surrounding DNA sequence. However, the epigenome at tissue-specific, distal regulatory regions was observed to be unusually prone to diverge following duplication, with particular sequence differences, altering known sequence motifs, found to be associated with divergence in patterns of DNA methylation and chromatin. Alu elements were found to have played a particularly prominent role in shaping human epigenome evolution, and we show that human-specific AluY insertion events are strongly linked to the evolution of the DNA methylation landscape and gene expression levels, including at key neurological genes in the human brain. Studying paralogous regions within the same sample enables the study of the links between genome and epigenome evolution while controlling for biological and technical variation. We show DNA methylation and chromatin divergence between duplicated regions are linked to the divergence of particular genetic motifs, with Alu elements having played a disproportionate role in the evolution of the epigenome in the human lineage. PMID:24966180

  20. Evolution Analysis of Simple Sequence Repeats in Plant Genome.

    PubMed

    Qin, Zhen; Wang, Yanping; Wang, Qingmei; Li, Aixian; Hou, Fuyun; Zhang, Liming

    2015-01-01

    Simple sequence repeats (SSRs) are widespread units on genome sequences, and play many important roles in plants. In order to reveal the evolution of plant genomes, we investigated the evolutionary regularities of SSRs during the evolution of plant species and the plant kingdom by analysis of twelve sequenced plant genome sequences. First, in the twelve studied plant genomes, the main SSRs were those which contain repeats of 1-3 nucleotides combination. Second, in mononucleotide SSRs, the A/T percentage gradually increased along with the evolution of plants (except for P. patens). With the increase of SSRs repeat number the percentage of A/T in C. reinhardtii had no significant change, while the percentage of A/T in terrestrial plants species gradually declined. Third, in dinucleotide SSRs, the percentage of AT/TA increased along with the evolution of plant kingdom and the repeat number increased in terrestrial plants species. This trend was more obvious in dicotyledon than monocotyledon. The percentage of CG/GC showed the opposite pattern to the AT/TA. Forth, in trinucleotide SSRs, the percentages of combinations including two or three A/T were in a rising trend along with the evolution of plant kingdom; meanwhile with the increase of SSRs repeat number in plants species, different species chose different combinations as dominant SSRs. SSRs in C. reinhardtii, P. patens, Z. mays and A. thaliana showed their specific patterns related to evolutionary position or specific changes of genome sequences. The results showed that, SSRs not only had the general pattern in the evolution of plant kingdom, but also were associated with the evolution of the specific genome sequence. The study of the evolutionary regularities of SSRs provided new insights for the analysis of the plant genome evolution.

  1. Co-evolution of upstream waves and accelerated ions at parallel shocks

    NASA Astrophysics Data System (ADS)

    Fujimoto, M.; Sugiyama, T.

    2016-12-01

    Shock waves in space plasmas have been considered as the agents for various particle acceleration phenomena. The basic idea behind shock acceleration is that particles are accelerated as they move back-and-forth across a shock front. Detailed studies of ion acceleration at the terrestrial bow shock have been performed, however, the restricted maximum energies attained prevent a straight-forward application of obtained knowledge to more energetic astrophysical situations. Here we show by a large-scale self-consistent particle simulation that the co-evolution of magnetic turbulence and accelerated ion population is the foundation for continuous operation of shock acceleration to ever higher energies. Magnetic turbulence is created by ions reflected back upstream of a parallel shock front. The co-evolution arises because more energetic ions excite waves of longer wavelengths, and because longer wavelength modes are capable of scattering (in the upstream) and reflecting (at the shock front) more energetic ions. Via carefully designed numerical experiments, we show very clearly that this picture is true.

  2. Acceleration techniques and their impact on arterial input function sampling: Non-accelerated versus view-sharing and compressed sensing sequences.

    PubMed

    Benz, Matthias R; Bongartz, Georg; Froehlich, Johannes M; Winkel, David; Boll, Daniel T; Heye, Tobias

    2018-07-01

    The aim was to investigate the variation of the arterial input function (AIF) within and between various DCE MRI sequences. A dynamic flow-phantom and steady signal reference were scanned on a 3T MRI using fast low angle shot (FLASH) 2d, FLASH3d (parallel imaging factor (P) = P0, P2, P4), volumetric interpolated breath-hold examination (VIBE) (P = P0, P3, P2 × 2, P2 × 3, P3 × 2), golden-angle radial sparse parallel imaging (GRASP), and time-resolved imaging with stochastic trajectories (TWIST). Signal over time curves were normalized and quantitatively analyzed by full width half maximum (FWHM) measurements to assess variation within and between sequences. The coefficient of variation (CV) for the steady signal reference ranged from 0.07-0.8%. The non-accelerated gradient echo FLASH2d, FLASH3d, and VIBE sequences showed low within sequence variation with 2.1%, 1.0%, and 1.6%. The maximum FWHM CV was 3.2% for parallel imaging acceleration (VIBE P2 × 3), 2.7% for GRASP and 9.1% for TWIST. The FWHM CV between sequences ranged from 8.5-14.4% for most non-accelerated/accelerated gradient echo sequences except 6.2% for FLASH3d P0 and 0.3% for FLASH3d P2; GRASP FWHM CV was 9.9% versus 28% for TWIST. MRI acceleration techniques vary in reproducibility and quantification of the AIF. Incomplete coverage of the k-space with TWIST as a representative of view-sharing techniques showed the highest variation within sequences and might be less suited for reproducible quantification of the AIF. Copyright © 2018 Elsevier B.V. All rights reserved.

  3. Repetitive sequences in plant nuclear DNA: types, distribution, evolution and function.

    PubMed

    Mehrotra, Shweta; Goyal, Vinod

    2014-08-01

    Repetitive DNA sequences are a major component of eukaryotic genomes and may account for up to 90% of the genome size. They can be divided into minisatellite, microsatellite and satellite sequences. Satellite DNA sequences are considered to be a fast-evolving component of eukaryotic genomes, comprising tandemly-arrayed, highly-repetitive and highly-conserved monomer sequences. The monomer unit of satellite DNA is 150-400 base pairs (bp) in length. Repetitive sequences may be species- or genus-specific, and may be centromeric or subtelomeric in nature. They exhibit cohesive and concerted evolution caused by molecular drive, leading to high sequence homogeneity. Repetitive sequences accumulate variations in sequence and copy number during evolution, hence they are important tools for taxonomic and phylogenetic studies, and are known as "tuning knobs" in the evolution. Therefore, knowledge of repetitive sequences assists our understanding of the organization, evolution and behavior of eukaryotic genomes. Repetitive sequences have cytoplasmic, cellular and developmental effects and play a role in chromosomal recombination. In the post-genomics era, with the introduction of next-generation sequencing technology, it is possible to evaluate complex genomes for analyzing repetitive sequences and deciphering the yet unknown functional potential of repetitive sequences. Copyright © 2014 The Authors. Production and hosting by Elsevier Ltd.. All rights reserved.

  4. Chromosome Evolution in Connection with Repetitive Sequences and Epigenetics in Plants

    PubMed Central

    Li, Shu-Fen; Su, Ting; Cheng, Guang-Qian; Wang, Bing-Xiao; Li, Xu; Deng, Chuan-Liang; Gao, Wu-Jun

    2017-01-01

    Chromosome evolution is a fundamental aspect of evolutionary biology. The evolution of chromosome size, structure and shape, number, and the change in DNA composition suggest the high plasticity of nuclear genomes at the chromosomal level. Repetitive DNA sequences, which represent a conspicuous fraction of every eukaryotic genome, particularly in plants, are found to be tightly linked with plant chromosome evolution. Different classes of repetitive sequences have distinct distribution patterns on the chromosomes. Mounting evidence shows that repetitive sequences may play multiple generative roles in shaping the chromosome karyotypes in plants. Furthermore, recent development in our understanding of the repetitive sequences and plant chromosome evolution has elucidated the involvement of a spectrum of epigenetic modification. In this review, we focused on the recent evidence relating to the distribution pattern of repetitive sequences in plant chromosomes and highlighted their potential relevance to chromosome evolution in plants. We also discussed the possible connections between evolution and epigenetic alterations in chromosome structure and repatterning, such as heterochromatin formation, centromere function, and epigenetic-associated transposable element inactivation. PMID:29064432

  5. Chromosome Evolution in Connection with Repetitive Sequences and Epigenetics in Plants.

    PubMed

    Li, Shu-Fen; Su, Ting; Cheng, Guang-Qian; Wang, Bing-Xiao; Li, Xu; Deng, Chuan-Liang; Gao, Wu-Jun

    2017-10-24

    Chromosome evolution is a fundamental aspect of evolutionary biology. The evolution of chromosome size, structure and shape, number, and the change in DNA composition suggest the high plasticity of nuclear genomes at the chromosomal level. Repetitive DNA sequences, which represent a conspicuous fraction of every eukaryotic genome, particularly in plants, are found to be tightly linked with plant chromosome evolution. Different classes of repetitive sequences have distinct distribution patterns on the chromosomes. Mounting evidence shows that repetitive sequences may play multiple generative roles in shaping the chromosome karyotypes in plants. Furthermore, recent development in our understanding of the repetitive sequences and plant chromosome evolution has elucidated the involvement of a spectrum of epigenetic modification. In this review, we focused on the recent evidence relating to the distribution pattern of repetitive sequences in plant chromosomes and highlighted their potential relevance to chromosome evolution in plants. We also discussed the possible connections between evolution and epigenetic alterations in chromosome structure and repatterning, such as heterochromatin formation, centromere function, and epigenetic-associated transposable element inactivation.

  6. Differential evolution-simulated annealing for multiple sequence alignment

    NASA Astrophysics Data System (ADS)

    Addawe, R. C.; Addawe, J. M.; Sueño, M. R. K.; Magadia, J. C.

    2017-10-01

    Multiple sequence alignments (MSA) are used in the analysis of molecular evolution and sequence structure relationships. In this paper, a hybrid algorithm, Differential Evolution - Simulated Annealing (DESA) is applied in optimizing multiple sequence alignments (MSAs) based on structural information, non-gaps percentage and totally conserved columns. DESA is a robust algorithm characterized by self-organization, mutation, crossover, and SA-like selection scheme of the strategy parameters. Here, the MSA problem is treated as a multi-objective optimization problem of the hybrid evolutionary algorithm, DESA. Thus, we name the algorithm as DESA-MSA. Simulated sequences and alignments were generated to evaluate the accuracy and efficiency of DESA-MSA using different indel sizes, sequence lengths, deletion rates and insertion rates. The proposed hybrid algorithm obtained acceptable solutions particularly for the MSA problem evaluated based on the three objectives.

  7. Accelerated and Adaptive Evolution of Yeast Sexual Adhesins

    PubMed Central

    Xie, Xianfa; Qiu, Wei-Gang; Lipke, Peter N.

    2011-01-01

    There is a recent emergence of interest in the genes involved in gametic recognition as drivers of reproductive isolation. The recent population genomic sequencing of two species of sexually primitive yeasts (Liti G, Carter DM, Moses AM, Warringer J, Parts L, James SA, Davey RP, Roberts IN, Burt A, Koufopanou V et al. [23 co-authors]. 2009. Population genomics of domestic and wild yeasts. Nature 458:337–341.) has provided data for systematic study of the roles these genes play in the early evolution of sex and speciation. Here, we discovered that among genes encoding cell surface proteins, the sexual adhesin genes have evolved significantly more rapidly than others, both within and between Saccharomyces cerevisiae and its closest relative S. paradoxus. This result was supported by analyses using the PAML pairwise model, a modified McDonald–Kreitman test, and the PAML branch model. Moreover, using a combination of a new statistic of neutrality, an information theory–based measure of evolutionary variability, and functional characterization of amino acid changes, we found that a higher proportion of amino acid changes are fixed in the sexual adhesins than in other proteins and a greater proportion of the fixed amino acid changes either between the two species or the two subgroups of S. paradoxus are functionally dissimilar or radically different. These results suggest that the accelerated evolution of sexual adhesin genes may facilitate speciation, or incipient speciation, and promote sexual selection in general. PMID:21633112

  8. Putative Independent Evolutionary Reversals from Genotypic to Temperature-Dependent Sex Determination are Associated with Accelerated Evolution of Sex-Determining Genes in Turtles.

    PubMed

    Literman, Robert; Burrett, Alexandria; Bista, Basanta; Valenzuela, Nicole

    2018-01-01

    The evolutionary lability of sex-determining mechanisms across the tree of life is well recognized, yet the extent of molecular changes that accompany these repeated transitions remain obscure. Most turtles retain the ancestral temperature-dependent sex determination (TSD) from which multiple transitions to genotypic sex determination (GSD) occurred independently, and two contrasting hypotheses posit the existence or absence of reversals back to TSD. Here we examined the molecular evolution of the coding regions of a set of gene regulators involved in gonadal development in turtles and several other vertebrates. We found slower molecular evolution in turtles and crocodilians compared to other vertebrates, but an acceleration in Trionychia turtles and at some phylogenetic branches demarcating major taxonomic diversification events. Of all gene classes examined, hormone signaling genes, and Srd5a1 in particular, evolve faster in many lineages and especially in turtles. Our data show that sex-linked genes do not follow a ubiquitous nor uniform pattern of molecular evolution. We then evaluated turtle nucleotide and protein evolution under two evolutionary hypotheses with or without GSD-to-TSD reversals, and found that when GSD-to-TSD reversals are considered, all transitional branches irrespective of direction, exhibit accelerated molecular evolution of nucleotide sequences, while GSD-to-TSD transitional branches also show acceleration in protein evolution. Significant changes in predicted secondary structure that may affect protein function were identified in three genes that exhibited hastened evolution in turtles compared to other vertebrates or in transitional versus non-transitional branches within turtles, rendering them candidates for a key role during SDM evolution in turtles.

  9. Determinants of the rate of protein sequence evolution

    PubMed Central

    Zhang, Jianzhi; Yang, Jian-Rong

    2015-01-01

    The rate and mechanism of protein sequence evolution have been central questions in evolutionary biology since the 1960s. Although the rate of protein sequence evolution depends primarily on the level of functional constraint, exactly what constitutes functional constraint has remained unclear. The increasing availability of genomic data has allowed for much needed empirical examinations on the nature of functional constraint. These studies found that the evolutionary rate of a protein is predominantly influenced by its expression level rather than functional importance. A combination of theoretical and empirical analyses have identified multiple mechanisms behind these observations and demonstrated a prominent role that selection against errors in molecular and cellular processes plays in protein evolution. PMID:26055156

  10. CD4+ T-cell recovery with suppressive ART-induced rapid sequence evolution in hepatitis C virus envelope but not NS3.

    PubMed

    Liu, Lin; Nardo, David; Li, Eric; Wang, Gary P

    2016-03-13

    CD4 T-cell depletion from HIV infection leads to a global decline in anti-hepatitis C virus (HCV) envelope neutralizing antibody (nAb) response, which may play a role in accelerating liver fibrosis. An increase in anti-HCV nAb titers has been reported during antiretroviral therapy (ART) but its impact on HCV remains poorly understood. The objective of this study is to determine the effects of ART on long-term HCV evolution. We examined HCV quasispecies structure and long-term evolution in HIV/HCV coinfected patients with ART-induced CD4 T-cell recovery, and compared with patients with CD4 T-cell depletion from delayed ART. We applied a single-variant sequencing (SVS) method to construct authentic viral quasispecies and compared sequence evolution in HCV envelope, the primary target for humoral immune responses, and NS3, a target for cellular immunity, between the two cohorts. The SVS method corrected biases known to skew the proportions of viral variants, revealing authentic HCV quasispeices structures. We observed higher rates of HCV envelope sequence evolution in patients with ART-induced CD4 T-cell recovery, compared with patients with CD4 T-cell depletion from delayed ART (P = 0.03). Evolutionary rates for NS3 were considerably lower than the rates for envelope (P < 0.01), with no significant difference observed between the two groups. ART-induced CD4 T-cell recovery results in rapid sequence evolution in HCV envelope, but not in NS3. These results suggest that suppressive ART disproportionally enhances HCV-specific humoral responses more than cellular responses, resulting in rapid sequence evolution in HCV envelope but not NS3.

  11. Accelerated Evolution and Functional Divergence of the Dim Light Visual Pigment Accompanies Cichlid Colonization of Central America.

    PubMed

    Hauser, Frances E; Ilves, Katriina L; Schott, Ryan K; Castiglione, Gianni M; López-Fernández, Hernán; Chang, Belinda S W

    2017-10-01

    Cichlids encompass one of the most diverse groups of fishes in South and Central America, and show extensive variation in life history, morphology, and colouration. While studies of visual system evolution in cichlids have focussed largely on the African rift lake species flocks, Neotropical cichlids offer a unique opportunity to investigate visual system evolution at broader temporal and geographic scales. South American cichlid colonization of Central America has likely promoted accelerated rates of morphological evolution in Central American lineages as they encountered reduced competition, renewed ecological opportunity, and novel aquatic habitats. To investigate whether such transitions have influenced molecular evolution of vision in Central American cichlids, we sequenced the dim-light rhodopsin gene in 101 Neotropical cichlid species, spanning the diversity of the clade. We find strong evidence for increased rates of evolution in Central American cichlid rhodopsin relative to South American lineages, and identify several sites under positive selection in rhodopsin that likely contribute to adaptation to different photic environments. We expressed a Neotropical cichlid rhodopsin protein invitro for the first time, and found that while its spectral tuning properties were characteristic of typical vertebrate rhodopsin pigments, the rate of decay of its active signalling form was much slower, consistent with dim light adaptation in other vertebrate rhodopsins. Using site-directed mutagenesis combined with spectroscopic assays, we found that a key amino acid substitution present in some Central American cichlids accelerates the rate of decay of active rhodopsin, which may mediate adaptation to clear water habitats. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  12. Transient Hypermutagenesis Accelerates the Evolution of Legume Endosymbionts following Horizontal Gene Transfer

    PubMed Central

    Remigi, Philippe; Capela, Delphine; Clerissi, Camille; Tasse, Léna; Torchet, Rachel; Bouchez, Olivier; Batut, Jacques; Cruveiller, Stéphane; Rocha, Eduardo P. C.; Masson-Boivin, Catherine

    2014-01-01

    Horizontal gene transfer (HGT) is an important mode of adaptation and diversification of prokaryotes and eukaryotes and a major event underlying the emergence of bacterial pathogens and mutualists. Yet it remains unclear how complex phenotypic traits such as the ability to fix nitrogen with legumes have successfully spread over large phylogenetic distances. Here we show, using experimental evolution coupled with whole genome sequencing, that co-transfer of imuABC error-prone DNA polymerase genes with key symbiotic genes accelerates the evolution of a soil bacterium into a legume symbiont. Following introduction of the symbiotic plasmid of Cupriavidus taiwanensis, the Mimosa symbiont, into pathogenic Ralstonia solanacearum we challenged transconjugants to become Mimosa symbionts through serial plant-bacteria co-cultures. We demonstrate that a mutagenesis imuABC cassette encoded on the C. taiwanensis symbiotic plasmid triggered a transient hypermutability stage in R. solanacearum transconjugants that occurred before the cells entered the plant. The generated burst in genetic diversity accelerated symbiotic adaptation of the recipient genome under plant selection pressure, presumably by improving the exploration of the fitness landscape. Finally, we show that plasmid imuABC cassettes are over-represented in rhizobial lineages harboring symbiotic plasmids. Our findings shed light on a mechanism that may have facilitated the dissemination of symbiotic competency among α- and β-proteobacteria in natura and provide evidence for the positive role of environment-induced mutagenesis in the acquisition of a complex lifestyle trait. We speculate that co-transfer of complex phenotypic traits with mutagenesis determinants might frequently enhance the ecological success of HGT. PMID:25181317

  13. Accelerated Evolution in the Death Galaxy

    NASA Astrophysics Data System (ADS)

    Austin, Robert; Tung, Chih-Kuan; Gong, Xiu-Quing; Lambert, Guillaume; Liao, David

    2010-03-01

    We recall 4 main guiding principles of evolution: 1) instability of defections, 2) stress induced non-random mutations, 3) genetic heterogeneity, and 4) fragmented populations. Our previous preliminary experiments have been relatively simple 1-D stress experiments. We are proceeding with 2-D experiments whose design is guided by these principles. Our new experiment we have dubbed the Death Galaxy because of it's use of these design principles. The ``galaxy'' name comes from the fact that the structure is designed as an interconnected array of micro-ecologies, these micro-ecologies are similar to the stars that comprise an astronomical galaxy, and provide the fragmented small populations. A gradient of the antibiotic Cipro is introduced across the galaxy, and we will present results which show how bacterial evolution resulting in resistance to Cipro is accelerated by the physics principles underlying the device.

  14. Archaebacterial rhodopsin sequences: Implications for evolution

    NASA Technical Reports Server (NTRS)

    Lanyi, J. K.

    1991-01-01

    It was proposed over 10 years ago that the archaebacteria represent a separate kingdom which diverged very early from the eubacteria and eukaryotes. It follows that investigations of archaebacterial characteristics might reveal features of early evolution. So far, two genes, one for bacteriorhodopsin and another for halorhodopsin, both from Halobacterium halobium, have been sequenced. We cloned and sequenced the gene coding for the polypeptide of another one of these rhodopsins, a halorhodopsin in Natronobacterium pharaonis. Peptide sequencing of cyanogen bromide fragments, and immuno-reactions of the protein and synthetic peptides derived from the C-terminal gene sequence, confirmed that the open reading frame was the structural gene for the pharaonis halorhodopsin polypeptide. The flanking DNA sequences of this gene, as well as those of other bacterial rhodopsins, were compared to previously proposed archaebacterial consensus sequences. In pairwise comparisons of the open reading frame with DNA sequences for bacterio-opsin and halo-opsin from Halobacterium halobium, silent divergences were calculated. These indicate very considerable evolutionary distance between each pair of genes, even in the dame organism. In spite of this, three protein sequences show extensive similarities, indicating strong selective pressures.

  15. Evolution of auroral acceleration region field-aligned current systems, plasma, and potentials observed by Cluster during substorms

    NASA Astrophysics Data System (ADS)

    Hull, A. J.; Chaston, C. C.; Fillingim, M. O.; Frey, H. U.; Goldstein, M. L.; Bonnell, J. W.; Mozer, F.

    2015-12-01

    The auroral acceleration region is an integral link in the chain of events that transpire during substorms, and the currents, plasma and electric fields undergo significant changes driven by complex dynamical processes deep in the magnetotail. The acceleration processes that occur therein accelerate and heat the plasma that ultimately leads to some of the most intense global substorm auroral displays. Though this region has garnered considerable attention, the temporal evolution of field-aligned current systems, associated acceleration processes, and resultant changes in the plasma constituents that occur during key stages of substorm development remain unclear. In this study we present a survey of Cluster traversals within and just above the auroral acceleration region (≤3 Re altitude) during substorms. Particular emphasis is on the spatial morphology and developmental sequence of auroral acceleration current systems, potentials and plasma constituents, with the aim of identifying controlling factors, and assessing auroral emmission consequences. Exploiting multi-point measurements from Cluster in combination with auroral imaging, we reveal the injection powered, Alfvenic nature of both the substorm onset and expansion of auroral particle acceleration. We show evidence that indicates substorm onsets are characterized by the gross-intensification and filamentation/striation of pre-existing large-scale current systems to smaller/dispersive scale Alfven waves. Such an evolutionary sequence has been suggested in theoretical models or single spacecraft data, but has not been demonstrated or characterized in multispacecraft observations until now. It is also shown how the Alfvenic variations over time may dissipate to form large-scale inverted-V structures characteristic of the quasi-static aurora. These findings suggest that, in addition to playing active roles in driving substorm aurora, inverted-V and Alfvenic acceleration processes are causally linked. Key

  16. Sedimentary sequence evolution in a Foredeep basin: Eastern Venezuela

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Bejarano, C.; Funes, D.; Sarzalho, S.

    1996-08-01

    Well log-seismic sequence stratigraphy analysis in the Eastern Venezuela Foreland Basin leads to study of the evolution of sedimentary sequences onto the Cretaceous-Paleocene passive margin. This basin comprises two different foredeep sub-basins: The Guarico subbasin to the west, older, and the Maturin sub-basin to the east, younger. A foredeep switching between these two sub-basins is observed at 12.5 m.y. Seismic interpretation and well log sections across the study area show sedimentary sequences with transgressive sands and coastal onlaps to the east-southeast for the Guarico sub-basin, as well as truncations below the switching sequence (12.5 m.y.), and the Maturin sub-basin showsmore » apparent coastal onlaps to the west-northwest, as well as a marine onlap (deeper water) in the west, where it starts to establish. Sequence stratigraphy analysis of these sequences with well logs allowed the study of the evolution of stratigraphic section from Paleocene to middle Miocene (68.0-12.0 m.y.). On the basis of well log patterns, the sequences were divided in regressive-transgressive-regressive sedimentary cycles caused by changes in relative sea level. Facies distributions were analyzed and the sequences were divided into simple sequences or sub- sequences of a greater frequencies than third order depositional sequences.« less

  17. Physical Scaffolding Accelerates the Evolution of Robot Behavior.

    PubMed

    Buckingham, David; Bongard, Josh

    2017-01-01

    In some evolutionary robotics experiments, evolved robots are transferred from simulation to reality, while sensor/motor data flows back from reality to improve the next transferral. We envision a generalization of this approach: a simulation-to-reality pipeline. In this pipeline, increasingly embodied agents flow up through a sequence of increasingly physically realistic simulators, while data flows back down to improve the next transferral between neighboring simulators; physical reality is the last link in this chain. As a first proof of concept, we introduce a two-link chain: A fast yet low-fidelity ( lo-fi) simulator hosts minimally embodied agents, which gradually evolve controllers and morphologies to colonize a slow yet high-fidelity ( hi-fi) simulator. The agents are thus physically scaffolded. We show here that, given the same computational budget, these physically scaffolded robots reach higher performance in the hi-fi simulator than do robots that only evolve in the hi-fi simulator, but only for a sufficiently difficult task. These results suggest that a simulation-to-reality pipeline may strike a good balance between accelerating evolution in simulation while anchoring the results in reality, free the investigator from having to prespecify the robot's morphology, and pave the way to scalable, automated, robot-generating systems.

  18. Evolution of Enzyme Superfamilies: Comprehensive Exploration of Sequence-Function Relationships.

    PubMed

    Baier, F; Copp, J N; Tokuriki, N

    2016-11-22

    The sequence and functional diversity of enzyme superfamilies have expanded through billions of years of evolution from a common ancestor. Understanding how protein sequence and functional "space" have expanded, at both the evolutionary and molecular level, is central to biochemistry, molecular biology, and evolutionary biology. Integrative approaches that examine protein sequence, structure, and function have begun to provide comprehensive views of the functional diversity and evolutionary relationships within enzyme superfamilies. In this review, we outline the recent advances in our understanding of enzyme evolution and superfamily functional diversity. We describe the tools that have been used to comprehensively analyze sequence relationships and to characterize sequence and function relationships. We also highlight recent large-scale experimental approaches that systematically determine the activity profiles across enzyme superfamilies. We identify several intriguing insights from this recent body of work. First, promiscuous activities are prevalent among extant enzymes. Second, many divergent proteins retain "function connectivity" via enzyme promiscuity, which can be used to probe the evolutionary potential and history of enzyme superfamilies. Finally, we discuss open questions regarding the intricacies of enzyme divergence, as well as potential research directions that will deepen our understanding of enzyme superfamily evolution.

  19. Accelerating pathway evolution by increasing the gene dosage of chromosomal segments.

    PubMed

    Tumen-Velasquez, Melissa; Johnson, Christopher W; Ahmed, Alaa; Dominick, Graham; Fulk, Emily M; Khanna, Payal; Lee, Sarah A; Schmidt, Alicia L; Linger, Jeffrey G; Eiteman, Mark A; Beckham, Gregg T; Neidle, Ellen L

    2018-06-18

    Experimental evolution is a critical tool in many disciplines, including metabolic engineering and synthetic biology. However, current methods rely on the chance occurrence of a key step that can dramatically accelerate evolution in natural systems, namely increased gene dosage. Our studies sought to induce the targeted amplification of chromosomal segments to facilitate rapid evolution. Since increased gene dosage confers novel phenotypes and genetic redundancy, we developed a method, Evolution by Amplification and Synthetic Biology (EASy), to create tandem arrays of chromosomal regions. In Acinetobacter baylyi , EASy was demonstrated on an important bioenergy problem, the catabolism of lignin-derived aromatic compounds. The initial focus on guaiacol (2-methoxyphenol), a common lignin degradation product, led to the discovery of Amycolatopsis genes ( gcoAB ) encoding a cytochrome P450 enzyme that converts guaiacol to catechol. However, chromosomal integration of gcoAB in Pseudomonas putida or A. baylyi did not enable guaiacol to be used as the sole carbon source despite catechol being a growth substrate. In ∼1,000 generations, EASy yielded alleles that in single chromosomal copy confer growth on guaiacol. Different variants emerged, including fusions between GcoA and CatA (catechol 1,2-dioxygenase). This study illustrates the power of harnessing chromosomal gene amplification to accelerate the evolution of desirable traits.

  20. Accelerated evolution of innate immunity proteins in social insects: adaptive evolution or relaxed constraint?

    PubMed

    Harpur, Brock A; Zayed, Amro

    2013-07-01

    The genomes of eusocial insects have a reduced complement of immune genes-an unusual finding considering that sociality provides ideal conditions for disease transmission. The following three hypotheses have been invoked to explain this finding: 1) social insects are attacked by fewer pathogens, 2) social insects have effective behavioral or 3) novel molecular mechanisms for combating pathogens. At the molecular level, these hypotheses predict that canonical innate immune pathways experience a relaxation of selective constraint. A recent study of several innate immune genes in ants and bees showed a pattern of accelerated amino acid evolution, which is consistent with either positive selection or a relaxation of constraint. We studied the population genetics of innate immune genes in the honey bee Apis mellifera by partially sequencing 13 genes from the bee's Toll pathway (∼10.5 kb) and 20 randomly chosen genes (∼16.5 kb) sequenced in 43 diploid workers. Relative to the random gene set, Toll pathway genes had significantly higher levels of amino acid replacement mutations segregating within A. mellifera and fixed between A. mellifera and A. cerana. However, levels of diversity and divergence at synonymous sites did not differ between the two gene sets. Although we detect strong signs of balancing selection on the pathogen recognition gene pgrp-sa, many of the genes in the Toll pathway show signatures of relaxed selective constraint. These results are consistent with the reduced complement of innate immune genes found in social insects and support the hypothesis that some aspect of eusociality renders canonical innate immunity superfluous.

  1. Comparative Analysis of Syntenic Genes in Grass Genomes Reveals Accelerated Rates of Gene Structure and Coding Sequence Evolution in Polyploid Wheat1[W][OA

    PubMed Central

    Akhunov, Eduard D.; Sehgal, Sunish; Liang, Hanquan; Wang, Shichen; Akhunova, Alina R.; Kaur, Gaganpreet; Li, Wanlong; Forrest, Kerrie L.; See, Deven; Šimková, Hana; Ma, Yaqin; Hayden, Matthew J.; Luo, Mingcheng; Faris, Justin D.; Doležel, Jaroslav; Gill, Bikram S.

    2013-01-01

    Cycles of whole-genome duplication (WGD) and diploidization are hallmarks of eukaryotic genome evolution and speciation. Polyploid wheat (Triticum aestivum) has had a massive increase in genome size largely due to recent WGDs. How these processes may impact the dynamics of gene evolution was studied by comparing the patterns of gene structure changes, alternative splicing (AS), and codon substitution rates among wheat and model grass genomes. In orthologous gene sets, significantly more acquired and lost exonic sequences were detected in wheat than in model grasses. In wheat, 35% of these gene structure rearrangements resulted in frame-shift mutations and premature termination codons. An increased codon mutation rate in the wheat lineage compared with Brachypodium distachyon was found for 17% of orthologs. The discovery of premature termination codons in 38% of expressed genes was consistent with ongoing pseudogenization of the wheat genome. The rates of AS within the individual wheat subgenomes (21%–25%) were similar to diploid plants. However, we uncovered a high level of AS pattern divergence between the duplicated homeologous copies of genes. Our results are consistent with the accelerated accumulation of AS isoforms, nonsynonymous mutations, and gene structure rearrangements in the wheat lineage, likely due to genetic redundancy created by WGDs. Whereas these processes mostly contribute to the degeneration of a duplicated genome and its diploidization, they have the potential to facilitate the origin of new functional variations, which, upon selection in the evolutionary lineage, may play an important role in the origin of novel traits. PMID:23124323

  2. Universal Sequence Replication, Reversible Polymerization and Early Functional Biopolymers: A Model for the Initiation of Prebiotic Sequence Evolution

    PubMed Central

    Walker, Sara Imari; Grover, Martha A.; Hud, Nicholas V.

    2012-01-01

    Many models for the origin of life have focused on understanding how evolution can drive the refinement of a preexisting enzyme, such as the evolution of efficient replicase activity. Here we present a model for what was, arguably, an even earlier stage of chemical evolution, when polymer sequence diversity was generated and sustained before, and during, the onset of functional selection. The model includes regular environmental cycles (e.g. hydration-dehydration cycles) that drive polymers between times of replication and functional activity, which coincide with times of different monomer and polymer diffusivity. Template-directed replication of informational polymers, which takes place during the dehydration stage of each cycle, is considered to be sequence-independent. New sequences are generated by spontaneous polymer formation, and all sequences compete for a finite monomer resource that is recycled via reversible polymerization. Kinetic Monte Carlo simulations demonstrate that this proposed prebiotic scenario provides a robust mechanism for the exploration of sequence space. Introduction of a polymer sequence with monomer synthetase activity illustrates that functional sequences can become established in a preexisting pool of otherwise non-functional sequences. Functional selection does not dominate system dynamics and sequence diversity remains high, permitting the emergence and spread of more than one functional sequence. It is also observed that polymers spontaneously form clusters in simulations where polymers diffuse more slowly than monomers, a feature that is reminiscent of a previous proposal that the earliest stages of life could have been defined by the collective evolution of a system-wide cooperation of polymer aggregates. Overall, the results presented demonstrate the merits of considering plausible prebiotic polymer chemistries and environments that would have allowed for the rapid turnover of monomer resources and for regularly varying monomer

  3. Prof. Hayashi's work on the pre-main sequence evolution and brown dwarfs

    NASA Astrophysics Data System (ADS)

    Nakano, Takenori

    2012-09-01

    Prof. Hayashi's work on the evolution of stars in the pre-main sequence stage is reviewed. The historical background and the process of finding the Hayashi phase are mentioned. The work on the evolution of low-mass stars is also reviewed including the determination of the bottom of the main sequence and evolution of brown dwarfs, and comparison is made with the other works in the same period.

  4. OncoNEM: inferring tumor evolution from single-cell sequencing data.

    PubMed

    Ross, Edith M; Markowetz, Florian

    2016-04-15

    Single-cell sequencing promises a high-resolution view of genetic heterogeneity and clonal evolution in cancer. However, methods to infer tumor evolution from single-cell sequencing data lag behind methods developed for bulk-sequencing data. Here, we present OncoNEM, a probabilistic method for inferring intra-tumor evolutionary lineage trees from somatic single nucleotide variants of single cells. OncoNEM identifies homogeneous cellular subpopulations and infers their genotypes as well as a tree describing their evolutionary relationships. In simulation studies, we assess OncoNEM's robustness and benchmark its performance against competing methods. Finally, we show its applicability in case studies of muscle-invasive bladder cancer and essential thrombocythemia.

  5. Comprehensive transcriptome analysis reveals accelerated genic evolution in a Tibet fish, Gymnodiptychus pachycheilus.

    PubMed

    Yang, Liandong; Wang, Ying; Zhang, Zhaolei; He, Shunping

    2014-12-26

    Elucidating the genetic mechanisms of organismal adaptation to the Tibetan Plateau at a genomic scale can provide insights into the process of adaptive evolution. Many highland species have been investigated and various candidate genes that may be responsible for highland adaptation have been identified. However, we know little about the genomic basis of adaptation to Tibet in fishes. Here, we performed transcriptome sequencing of a schizothoracine fish (Gymnodiptychus pachycheilus) and used it to identify potential genetic mechanisms of highland adaptation. We obtained totally 66,105 assembled unigenes, of which 7,232 were assigned as putative one-to-one orthologs in zebrafish. Comparative gene annotations from several species indicated that at least 350 genes lost and 41 gained since the divergence between G. pachycheilus and zebrafish. An analysis of 6,324 orthologs among zebrafish, fugu, medaka, and spotted gar identified consistent evidence for genome-wide accelerated evolution in G. pachycheilus and only the terminal branch of G. pachycheilus had an elevated Ka/Ks ratio than the ancestral branch. Many functional categories related to hypoxia and energy metabolism exhibited rapid evolution in G. pachycheilus relative to zebrafish. Genes showing signature of rapid evolution and positive selection in the G. pachycheilus lineage were also enriched in functions associated with energy metabolism and hypoxia. The first genomic resources for fish in the Tibetan Plateau and evolutionary analyses provided some novel insights into highland adaptation in fishes and served as a foundation for future studies aiming to identify candidate genes underlying the genetic bases of adaptation to Tibet in fishes. © The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  6. Mitochondrial-nuclear interactions and accelerated compensatory evolution: evidence from the primate cytochrome C oxidase complex.

    PubMed

    Osada, Naoki; Akashi, Hiroshi

    2012-01-01

    Accelerated rates of mitochondrial protein evolution have been proposed to reflect Darwinian coadaptation for efficient energy production for mammalian flight and brain activity. However, several features of mammalian mtDNA (absence of recombination, small effective population size, and high mutation rate) promote genome degradation through the accumulation of weakly deleterious mutations. Here, we present evidence for "compensatory" adaptive substitutions in nuclear DNA- (nDNA) encoded mitochondrial proteins to prevent fitness decline in primate mitochondrial protein complexes. We show that high mutation rate and small effective population size, key features of primate mitochondrial genomes, can accelerate compensatory adaptive evolution in nDNA-encoded genes. We combine phylogenetic information and the 3D structure of the cytochrome c oxidase (COX) complex to test for accelerated compensatory changes among interacting sites. Physical interactions among mtDNA- and nDNA-encoded components are critical in COX evolution; amino acids in close physical proximity in the 3D structure show a strong tendency for correlated evolution among lineages. Only nuclear-encoded components of COX show evidence for positive selection and adaptive nDNA-encoded changes tend to follow mtDNA-encoded amino acid changes at nearby sites in the 3D structure. This bias in the temporal order of substitutions supports compensatory weak selection as a major factor in accelerated primate COX evolution.

  7. The Evolution of Bony Vertebrate Enhancers at Odds with Their Coding Sequence Landscape.

    PubMed

    Yousaf, Aisha; Sohail Raza, Muhammad; Ali Abbasi, Amir

    2015-08-06

    Enhancers lie at the heart of transcriptional and developmental gene regulation. Therefore, changes in enhancer sequences usually disrupt the target gene expression and result in disease phenotypes. Despite the well-established role of enhancers in development and disease, evolutionary sequence studies are lacking. The current study attempts to unravel the puzzle of bony vertebrates' conserved noncoding elements (CNE) enhancer evolution. Bayesian phylogenetics of enhancer sequences spotlights promising interordinal relationships among placental mammals, proposing a closer relationship between humans and laurasiatherians while placing rodents at the basal position. Clock-based estimates of enhancer evolution provided a dynamic picture of interspecific rate changes across the bony vertebrate lineage. Moreover, coelacanth in the study augmented our appreciation of the vertebrate cis-regulatory evolution during water-land transition. Intriguingly, we observed a pronounced upsurge in enhancer evolution in land-dwelling vertebrates. These novel findings triggered us to further investigate the evolutionary trend of coding as well as CNE nonenhancer repertoires, to highlight the relative evolutionary dynamics of diverse genomic landscapes. Surprisingly, the evolutionary rates of enhancer sequences were clearly at odds with those of the coding and the CNE nonenhancer sequences during vertebrate adaptation to land, with land vertebrates exhibiting significantly reduced rates of coding sequence evolution in comparison to their fast evolving regulatory landscape. The observed variation in tetrapod cis-regulatory elements caused the fine-tuning of associated gene regulatory networks. Therefore, the increased evolutionary rate of tetrapods' enhancer sequences might be responsible for the variation in developmental regulatory circuits during the process of vertebrate adaptation to land. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for

  8. CAFE: aCcelerated Alignment-FrEe sequence analysis.

    PubMed

    Lu, Yang Young; Tang, Kujin; Ren, Jie; Fuhrman, Jed A; Waterman, Michael S; Sun, Fengzhu

    2017-07-03

    Alignment-free genome and metagenome comparisons are increasingly important with the development of next generation sequencing (NGS) technologies. Recently developed state-of-the-art k-mer based alignment-free dissimilarity measures including CVTree, $d_2^*$ and $d_2^S$ are more computationally expensive than measures based solely on the k-mer frequencies. Here, we report a standalone software, aCcelerated Alignment-FrEe sequence analysis (CAFE), for efficient calculation of 28 alignment-free dissimilarity measures. CAFE allows for both assembled genome sequences and unassembled NGS shotgun reads as input, and wraps the output in a standard PHYLIP format. In downstream analyses, CAFE can also be used to visualize the pairwise dissimilarity measures, including dendrograms, heatmap, principal coordinate analysis and network display. CAFE serves as a general k-mer based alignment-free analysis platform for studying the relationships among genomes and metagenomes, and is freely available at https://github.com/younglululu/CAFE. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  9. Comparative Genomics Reveals Accelerated Evolution in Conserved Pathways during the Diversification of Anole Lizards.

    PubMed

    Tollis, Marc; Hutchins, Elizabeth D; Stapley, Jessica; Rupp, Shawn M; Eckalbar, Walter L; Maayan, Inbar; Lasku, Eris; Infante, Carlos R; Dennis, Stuart R; Robertson, Joel A; May, Catherine M; Crusoe, Michael R; Bermingham, Eldredge; DeNardo, Dale F; Hsieh, Shi-Tong Tonia; Kulathinal, Rob J; McMillan, William Owen; Menke, Douglas B; Pratt, Stephen C; Rawls, Jeffery Alan; Sanjur, Oris; Wilson-Rawls, Jeanne; Wilson Sayres, Melissa A; Fisher, Rebecca E; Kusumi, Kenro

    2018-02-01

    Squamates include all lizards and snakes, and display some of the most diverse and extreme morphological adaptations among vertebrates. However, compared with birds and mammals, relatively few resources exist for comparative genomic analyses of squamates, hampering efforts to understand the molecular bases of phenotypic diversification in such a speciose clade. In particular, the ∼400 species of anole lizard represent an extensive squamate radiation. Here, we sequence and assemble the draft genomes of three anole species-Anolis frenatus, Anolis auratus, and Anolis apletophallus-for comparison with the available reference genome of Anolis carolinensis. Comparative analyses reveal a rapid background rate of molecular evolution consistent with a model of punctuated equilibrium, and strong purifying selection on functional genomic elements in anoles. We find evidence for accelerated evolution in genes involved in behavior, sensory perception, and reproduction, as well as in genes regulating limb bud development and hindlimb specification. Morphometric analyses of anole fore and hindlimbs corroborated these findings. We detect signatures of positive selection across several genes related to the development and regulation of the forebrain, hormones, and the iguanian lizard dewlap, suggesting molecular changes underlying behavioral adaptations known to reinforce species boundaries were a key component in the diversification of anole lizards. © The Author(s) 2018. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  10. Complete Genome Sequence of Magnetospirillum gryphiswaldense MSR-1

    PubMed Central

    Wang, Xu; Wang, Qing; Zhang, Weijia; Wang, Yinjia; Li, Li; Wen, Tong; Zhang, Tongwei; Zhang, Yang; Xu, Jun; Hu, Junying; Li, Shuqi; Liu, Lingzi; Liu, Jinxin; Jiang, Wei; Tian, Jiesheng; Wang, Lei; Li, Jilun

    2014-01-01

    We report the complete genomic sequence of Magnetospirillum gryphiswaldense MSR-1 (DSM 6361), a type strain of the genus Magnetospirillum belonging to the Alphaproteobacteria. Compared to the reported draft sequence, extensive rearrangements and differences were found, indicating high genomic flexibility and “domestication” by accelerated evolution of the strain upon repeated passaging. PMID:24625872

  11. The Role of the Y-Chromosome in the Establishment of Murine Hybrid Dysgenesis and in the Analysis of the Nucleotide Sequence Organization, Genetic Transmission and Evolution of Repeated Sequences.

    NASA Astrophysics Data System (ADS)

    Nallaseth, Ferez Soli

    The Y-chromosome presents a unique cytogenetic framework for the evolution of nucleotide sequences. Alignment of nine Y-chromosomal fragments in their increasing Y-specific/non Y-specific (male/female) sequence divergence ratios was directly and inversely related to their interspersion on these two respective genomic fractions. Sequence analysis confirmed a direct relationship between divergence ratios and the Alu, LINE-1, Satellite and their derivative oligonucleotide contents. Thus their relocation on the Y-chromosome is followed by sequence divergence rather than the well documented concerted evolution of these non-coding progenitor repeated sequences. Five of the nine Y-chromosomal fragments are non-pseudoautosomal and transcribed into heterogeneous PolyA^+ RNA and thus can be retrotransposed. Evolutionary and computer analysis identified homologous oligonucleotide tracts in several human loci suggesting common and random mechanistic origins. Dysgenic genomes represent the accelerated evolution driving sequence divergence (McClintock, 1984). Sex reversal and sterility characterizing dysgenesis occurs in C57BL/6JY ^{rm Pos} but not in 129/SvY^{rm Pos} derivative strains. High frequency, random, multi-locus deletion products of the feral Y^{ rm Pos}-chromosome are generated in the germlines of F1(C57BL/6J X 129/SvY^{ rm Pos})(male) and C57BL/6JY ^{rm Pos}(male) but not in 129/SvY^{rm Pos}(male). Equal, 10^{-1}, 10^ {-2}, and 0 copies (relative to males) of Y^{rm Pos}-specific deletion products respectively characterize C57BL/6JY ^{rm Pos} (HC), (LC), (T) and (F) females. The testes determining loci of inactive Y^{rm Pos}-chromosomes in C57BL/6JY^{rm Pos} HC females are the preferentially deleted/rearranged Y ^{rm Pos}-sequences. Disruption of regulation of plasma testosterone and hepatic MUP-A mRNA levels, TRD of a 4.7 Kbp EcoR1 fragment suggest disruption of autosomal/X-chromosomal sequences. These data and the highly repeated progenitor (Alu, GATA, LINE-1

  12. Genes involved in convergent evolution of eusociality in bees

    PubMed Central

    Woodard, S. Hollis; Fischman, Brielle J.; Venkat, Aarti; Hudson, Matt E.; Varala, Kranthi; Cameron, Sydney A.; Clark, Andrew G.; Robinson, Gene E.

    2011-01-01

    Eusociality has arisen independently at least 11 times in insects. Despite this convergence, there are striking differences among eusocial lifestyles, ranging from species living in small colonies with overt conflict over reproduction to species in which colonies contain hundreds of thousands of highly specialized sterile workers produced by one or a few queens. Although the evolution of eusociality has been intensively studied, the genetic changes involved in the evolution of eusociality are relatively unknown. We examined patterns of molecular evolution across three independent origins of eusociality by sequencing transcriptomes of nine socially diverse bee species and combining these data with genome sequence from the honey bee Apis mellifera to generate orthologous sequence alignments for 3,647 genes. We found a shared set of 212 genes with a molecular signature of accelerated evolution across all eusocial lineages studied, as well as unique sets of 173 and 218 genes with a signature of accelerated evolution specific to either highly or primitively eusocial lineages, respectively. These results demonstrate that convergent evolution can involve a mosaic pattern of molecular changes in both shared and lineage-specific sets of genes. Genes involved in signal transduction, gland development, and carbohydrate metabolism are among the most prominent rapidly evolving genes in eusocial lineages. These findings provide a starting point for linking specific genetic changes to the evolution of eusociality. PMID:21482769

  13. Biophysical and structural considerations for protein sequence evolution

    PubMed Central

    2011-01-01

    Background Protein sequence evolution is constrained by the biophysics of folding and function, causing interdependence between interacting sites in the sequence. However, current site-independent models of sequence evolutions do not take this into account. Recent attempts to integrate the influence of structure and biophysics into phylogenetic models via statistical/informational approaches have not resulted in expected improvements in model performance. This suggests that further innovations are needed for progress in this field. Results Here we develop a coarse-grained physics-based model of protein folding and binding function, and compare it to a popular informational model. We find that both models violate the assumption of the native sequence being close to a thermodynamic optimum, causing directional selection away from the native state. Sampling and simulation show that the physics-based model is more specific for fold-defining interactions that vary less among residue type. The informational model diffuses further in sequence space with fewer barriers and tends to provide less support for an invariant sites model, although amino acid substitutions are generally conservative. Both approaches produce sequences with natural features like dN/dS < 1 and gamma-distributed rates across sites. Conclusions Simple coarse-grained models of protein folding can describe some natural features of evolving proteins but are currently not accurate enough to use in evolutionary inference. This is partly due to improper packing of the hydrophobic core. We suggest possible improvements on the representation of structure, folding energy, and binding function, as regards both native and non-native conformations, and describe a large number of possible applications for such a model. PMID:22171550

  14. Conserved noncoding sequences conserve biological networks and influence genome evolution.

    PubMed

    Xie, Jianbo; Qian, Kecheng; Si, Jingna; Xiao, Liang; Ci, Dong; Zhang, Deqiang

    2018-05-01

    Comparative genomics approaches have identified numerous conserved cis-regulatory sequences near genes in plant genomes. Despite the identification of these conserved noncoding sequences (CNSs), our knowledge of their functional importance and selection remains limited. Here, we used a combination of DNA methylome analysis, microarray expression analyses, and functional annotation to study these sequences in the model tree Populus trichocarpa. Methylation in CG contexts and non-CG contexts was lower in CNSs, particularly CNSs in the 5'-upstream regions of genes, compared with other sites in the genome. We observed that CNSs are enriched in genes with transcription and binding functions, and this also associated with syntenic genes and those from whole-genome duplications, suggesting that cis-regulatory sequences play a key role in genome evolution. We detected a significant positive correlation between CNS number and protein interactions, suggesting that CNSs may have roles in the evolution and maintenance of biological networks. The divergence of CNSs indicates that duplication-degeneration-complementation drives the subfunctionalization of a proportion of duplicated genes from whole-genome duplication. Furthermore, population genomics confirmed that most CNSs are under strong purifying selection and only a small subset of CNSs shows evidence of adaptive evolution. These findings provide a foundation for future studies exploring these key genomic features in the maintenance of biological networks, local adaptation, and transcription.

  15. The evolution of transcriptional regulation in eukaryotes

    NASA Technical Reports Server (NTRS)

    Wray, Gregory A.; Hahn, Matthew W.; Abouheif, Ehab; Balhoff, James P.; Pizer, Margaret; Rockman, Matthew V.; Romano, Laura A.

    2003-01-01

    Gene expression is central to the genotype-phenotype relationship in all organisms, and it is an important component of the genetic basis for evolutionary change in diverse aspects of phenotype. However, the evolution of transcriptional regulation remains understudied and poorly understood. Here we review the evolutionary dynamics of promoter, or cis-regulatory, sequences and the evolutionary mechanisms that shape them. Existing evidence indicates that populations harbor extensive genetic variation in promoter sequences, that a substantial fraction of this variation has consequences for both biochemical and organismal phenotype, and that some of this functional variation is sorted by selection. As with protein-coding sequences, rates and patterns of promoter sequence evolution differ considerably among loci and among clades for reasons that are not well understood. Studying the evolution of transcriptional regulation poses empirical and conceptual challenges beyond those typically encountered in analyses of coding sequence evolution: promoter organization is much less regular than that of coding sequences, and sequences required for the transcription of each locus reside at multiple other loci in the genome. Because of the strong context-dependence of transcriptional regulation, sequence inspection alone provides limited information about promoter function. Understanding the functional consequences of sequence differences among promoters generally requires biochemical and in vivo functional assays. Despite these challenges, important insights have already been gained into the evolution of transcriptional regulation, and the pace of discovery is accelerating.

  16. Comparative genome sequencing of Drosophila pseudoobscura: Chromosomal, gene, and cis-element evolution

    PubMed Central

    Richards, Stephen; Liu, Yue; Bettencourt, Brian R.; Hradecky, Pavel; Letovsky, Stan; Nielsen, Rasmus; Thornton, Kevin; Hubisz, Melissa J.; Chen, Rui; Meisel, Richard P.; Couronne, Olivier; Hua, Sujun; Smith, Mark A.; Zhang, Peili; Liu, Jing; Bussemaker, Harmen J.; van Batenburg, Marinus F.; Howells, Sally L.; Scherer, Steven E.; Sodergren, Erica; Matthews, Beverly B.; Crosby, Madeline A.; Schroeder, Andrew J.; Ortiz-Barrientos, Daniel; Rives, Catharine M.; Metzker, Michael L.; Muzny, Donna M.; Scott, Graham; Steffen, David; Wheeler, David A.; Worley, Kim C.; Havlak, Paul; Durbin, K. James; Egan, Amy; Gill, Rachel; Hume, Jennifer; Morgan, Margaret B.; Miner, George; Hamilton, Cerissa; Huang, Yanmei; Waldron, Lenée; Verduzco, Daniel; Clerc-Blankenburg, Kerstin P.; Dubchak, Inna; Noor, Mohamed A.F.; Anderson, Wyatt; White, Kevin P.; Clark, Andrew G.; Schaeffer, Stephen W.; Gelbart, William; Weinstock, George M.; Gibbs, Richard A.

    2005-01-01

    We have sequenced the genome of a second Drosophila species, Drosophila pseudoobscura, and compared this to the genome sequence of Drosophila melanogaster, a primary model organism. Throughout evolution the vast majority of Drosophila genes have remained on the same chromosome arm, but within each arm gene order has been extensively reshuffled, leading to a minimum of 921 syntenic blocks shared between the species. A repetitive sequence is found in the D. pseudoobscura genome at many junctions between adjacent syntenic blocks. Analysis of this novel repetitive element family suggests that recombination between offset elements may have given rise to many paracentric inversions, thereby contributing to the shuffling of gene order in the D. pseudoobscura lineage. Based on sequence similarity and synteny, 10,516 putative orthologs have been identified as a core gene set conserved over 25–55 million years (Myr) since the pseudoobscura/melanogaster divergence. Genes expressed in the testes had higher amino acid sequence divergence than the genome-wide average, consistent with the rapid evolution of sex-specific proteins. Cis-regulatory sequences are more conserved than random and nearby sequences between the species—but the difference is slight, suggesting that the evolution of cis-regulatory elements is flexible. Overall, a pattern of repeat-mediated chromosomal rearrangement, and high coadaptation of both male genes and cis-regulatory sequences emerges as important themes of genome divergence between these species of Drosophila. PMID:15632085

  17. Beyond Reasonable Doubt: Evolution from DNA Sequences

    PubMed Central

    Penny, David

    2013-01-01

    We demonstrate quantitatively that, as predicted by evolutionary theory, sequences of homologous proteins from different species converge as we go further and further back in time. The converse, a non-evolutionary model can be expressed as probabilities, and the test works for chloroplast, nuclear and mitochondrial sequences, as well as for sequences that diverged at different time depths. Even on our conservative test, the probability that chance could produce the observed levels of ancestral convergence for just one of the eight datasets of 51 proteins is ≈1×10−19 and combined over 8 datasets is ≈1×10−132. By comparison, there are about 1080 protons in the universe, hence the probability that the sequences could have been produced by a process involving unrelated ancestral sequences is about 1050 lower than picking, among all protons, the same proton at random twice in a row. A non-evolutionary control model shows no convergence, and only a small number of parameters are required to account for the observations. It is time that that researchers insisted that doubters put up testable alternatives to evolution. PMID:23950906

  18. Comparative Genomics Reveals Accelerated Evolution in Conserved Pathways during the Diversification of Anole Lizards

    PubMed Central

    Tollis, Marc; Hutchins, Elizabeth D; Stapley, Jessica; Rupp, Shawn M; Eckalbar, Walter L; Maayan, Inbar; Lasku, Eris; Infante, Carlos R; Dennis, Stuart R; Robertson, Joel A; May, Catherine M; Bermingham, Eldredge; DeNardo, Dale F; Hsieh, Shi-Tong Tonia; Kulathinal, Rob J; McMillan, William Owen; Menke, Douglas B; Pratt, Stephen C; Rawls, Jeffery Alan; Sanjur, Oris; Wilson-Rawls, Jeanne; Wilson Sayres, Melissa A; Fisher, Rebecca E

    2018-01-01

    Abstract Squamates include all lizards and snakes, and display some of the most diverse and extreme morphological adaptations among vertebrates. However, compared with birds and mammals, relatively few resources exist for comparative genomic analyses of squamates, hampering efforts to understand the molecular bases of phenotypic diversification in such a speciose clade. In particular, the ∼400 species of anole lizard represent an extensive squamate radiation. Here, we sequence and assemble the draft genomes of three anole species—Anolis frenatus, Anolis auratus, and Anolis apletophallus—for comparison with the available reference genome of Anolis carolinensis. Comparative analyses reveal a rapid background rate of molecular evolution consistent with a model of punctuated equilibrium, and strong purifying selection on functional genomic elements in anoles. We find evidence for accelerated evolution in genes involved in behavior, sensory perception, and reproduction, as well as in genes regulating limb bud development and hindlimb specification. Morphometric analyses of anole fore and hindlimbs corroborated these findings. We detect signatures of positive selection across several genes related to the development and regulation of the forebrain, hormones, and the iguanian lizard dewlap, suggesting molecular changes underlying behavioral adaptations known to reinforce species boundaries were a key component in the diversification of anole lizards. PMID:29360978

  19. Rapid evolution accelerates plant population spread in fragmented experimental landscapes.

    PubMed

    Williams, Jennifer L; Kendall, Bruce E; Levine, Jonathan M

    2016-07-29

    Predicting the speed of biological invasions and native species migrations requires an understanding of the ecological and evolutionary dynamics of spreading populations. Theory predicts that evolution can accelerate species' spread velocity, but how landscape patchiness--an important control over traits under selection--influences this process is unknown. We manipulated the response to selection in populations of a model plant species spreading through replicated experimental landscapes of varying patchiness. After six generations of change, evolving populations spread 11% farther than nonevolving populations in continuously favorable landscapes and 200% farther in the most fragmented landscapes. The greater effect of evolution on spread in patchier landscapes was consistent with the evolution of dispersal and competitive ability. Accounting for evolutionary change may be critical when predicting the velocity of range expansions. Copyright © 2016, American Association for the Advancement of Science.

  20. Learning about evolution from sequence data

    NASA Astrophysics Data System (ADS)

    Dayarian, Adel; Shraiman, Boris

    2012-02-01

    Recent advances in sequencing and in laboratory evolution experiments have made possible to obtain quantitative data on genetic diversity of populations and on the dynamics of evolution. This dynamics is shaped by the interplay between selection acting on beneficial and deleterious mutations and recombination which reshuffles genotypes. Mounting evidence suggests that natural populations harbor extensive fitness diversity, yet most of the currently available tools for analyzing polymorphism data are based on the neutral theory. Our aim is to develop methods to analyze genomic data for populations in the presence of the above-mentioned factors. We consider different evolutionary regimes - Muller's ratchet, mutation-recombination-selection balance and positive adaption rate - and revisit a number of observables considered in the nearly-neutral theory of evolution. In particular, we examine the coalescent structure in the presence of recombination and calculate quantities such as the distribution of the coalescent times along the genome, the distribution of haplotype block sizes and the correlation between ancestors of different loci along the genome. In addition, we characterize the probability and time of fixation of mutations as a function of their fitness effect.

  1. Rapid evolution of cis-regulatory sequences via local point mutations

    NASA Technical Reports Server (NTRS)

    Stone, J. R.; Wray, G. A.

    2001-01-01

    Although the evolution of protein-coding sequences within genomes is well understood, the same cannot be said of the cis-regulatory regions that control transcription. Yet, changes in gene expression are likely to constitute an important component of phenotypic evolution. We simulated the evolution of new transcription factor binding sites via local point mutations. The results indicate that new binding sites appear and become fixed within populations on microevolutionary timescales under an assumption of neutral evolution. Even combinations of two new binding sites evolve very quickly. We predict that local point mutations continually generate considerable genetic variation that is capable of altering gene expression.

  2. Synthetic biology for the directed evolution of protein biocatalysts: navigating sequence space intelligently

    PubMed Central

    Currin, Andrew; Swainston, Neil; Day, Philip J.

    2015-01-01

    The amino acid sequence of a protein affects both its structure and its function. Thus, the ability to modify the sequence, and hence the structure and activity, of individual proteins in a systematic way, opens up many opportunities, both scientifically and (as we focus on here) for exploitation in biocatalysis. Modern methods of synthetic biology, whereby increasingly large sequences of DNA can be synthesised de novo, allow an unprecedented ability to engineer proteins with novel functions. However, the number of possible proteins is far too large to test individually, so we need means for navigating the ‘search space’ of possible protein sequences efficiently and reliably in order to find desirable activities and other properties. Enzymologists distinguish binding (K d) and catalytic (k cat) steps. In a similar way, judicious strategies have blended design (for binding, specificity and active site modelling) with the more empirical methods of classical directed evolution (DE) for improving k cat (where natural evolution rarely seeks the highest values), especially with regard to residues distant from the active site and where the functional linkages underpinning enzyme dynamics are both unknown and hard to predict. Epistasis (where the ‘best’ amino acid at one site depends on that or those at others) is a notable feature of directed evolution. The aim of this review is to highlight some of the approaches that are being developed to allow us to use directed evolution to improve enzyme properties, often dramatically. We note that directed evolution differs in a number of ways from natural evolution, including in particular the available mechanisms and the likely selection pressures. Thus, we stress the opportunities afforded by techniques that enable one to map sequence to (structure and) activity in silico, as an effective means of modelling and exploring protein landscapes. Because known landscapes may be assessed and reasoned about as a whole

  3. Evolution of dispersal and life history interact to drive accelerating spread of an invasive species.

    PubMed

    Perkins, T Alex; Phillips, Benjamin L; Baskett, Marissa L; Hastings, Alan

    2013-08-01

    Populations on the edge of an expanding range are subject to unique evolutionary pressures acting on their life-history and dispersal traits. Empirical evidence and theory suggest that traits there can evolve rapidly enough to interact with ecological dynamics, potentially giving rise to accelerating spread. Nevertheless, which of several evolutionary mechanisms drive this interaction between evolution and spread remains an open question. We propose an integrated theoretical framework for partitioning the contributions of different evolutionary mechanisms to accelerating spread, and we apply this model to invasive cane toads in northern Australia. In doing so, we identify a previously unrecognised evolutionary process that involves an interaction between life-history and dispersal evolution during range shift. In roughly equal parts, life-history evolution, dispersal evolution and their interaction led to a doubling of distance spread by cane toads in our model, highlighting the potential importance of multiple evolutionary processes in the dynamics of range expansion. © 2013 John Wiley & Sons Ltd/CNRS.

  4. Interstitial telomeric sequences in vertebrate chromosomes: Origin, function, instability and evolution.

    PubMed

    Bolzán, Alejandro D

    2017-07-01

    By definition, telomeric sequences are located at the very ends or terminal regions of chromosomes. However, several vertebrate species show blocks of (TTAGGG)n repeats present in non-terminal regions of chromosomes, the so-called interstitial telomeric sequences (ITSs), interstitial telomeric repeats or interstitial telomeric bands, which include those intrachromosomal telomeric-like repeats located near (pericentromeric ITSs) or within the centromere (centromeric ITSs) and those telomeric repeats located between the centromere and the telomere (i.e., truly interstitial telomeric sequences) of eukaryotic chromosomes. According with their sequence organization, localization and flanking sequences, ITSs can be classified into four types: 1) short ITSs, 2) subtelomeric ITSs, 3) fusion ITSs, and 4) heterochromatic ITSs. The first three types have been described mainly in the human genome, whereas heterochromatic ITSs have been found in several vertebrate species but not in humans. Several lines of evidence suggest that ITSs play a significant role in genome instability and evolution. This review aims to summarize our current knowledge about the origin, function, instability and evolution of these telomeric-like repeats in vertebrate chromosomes. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Clonal evolution in breast cancer revealed by single nucleus genome sequencing.

    PubMed

    Wang, Yong; Waters, Jill; Leung, Marco L; Unruh, Anna; Roh, Whijae; Shi, Xiuqing; Chen, Ken; Scheet, Paul; Vattathil, Selina; Liang, Han; Multani, Asha; Zhang, Hong; Zhao, Rui; Michor, Franziska; Meric-Bernstam, Funda; Navin, Nicholas E

    2014-08-14

    Sequencing studies of breast tumour cohorts have identified many prevalent mutations, but provide limited insight into the genomic diversity within tumours. Here we developed a whole-genome and exome single cell sequencing approach called nuc-seq that uses G2/M nuclei to achieve 91% mean coverage breadth. We applied this method to sequence single normal and tumour nuclei from an oestrogen-receptor-positive (ER(+)) breast cancer and a triple-negative ductal carcinoma. In parallel, we performed single nuclei copy number profiling. Our data show that aneuploid rearrangements occurred early in tumour evolution and remained highly stable as the tumour masses clonally expanded. In contrast, point mutations evolved gradually, generating extensive clonal diversity. Using targeted single-molecule sequencing, many of the diverse mutations were shown to occur at low frequencies (<10%) in the tumour mass. Using mathematical modelling we found that the triple-negative tumour cells had an increased mutation rate (13.3×), whereas the ER(+) tumour cells did not. These findings have important implications for the diagnosis, therapeutic treatment and evolution of chemoresistance in breast cancer.

  6. CAFE: aCcelerated Alignment-FrEe sequence analysis

    PubMed Central

    Lu, Yang Young; Tang, Kujin; Ren, Jie; Fuhrman, Jed A.; Waterman, Michael S.

    2017-01-01

    Abstract Alignment-free genome and metagenome comparisons are increasingly important with the development of next generation sequencing (NGS) technologies. Recently developed state-of-the-art k-mer based alignment-free dissimilarity measures including CVTree, \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$d_2^*$\\end{document} and \\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{upgreek} \\usepackage{mathrsfs} \\setlength{\\oddsidemargin}{-69pt} \\begin{document} }{}$d_2^S$\\end{document} are more computationally expensive than measures based solely on the k-mer frequencies. Here, we report a standalone software, aCcelerated Alignment-FrEe sequence analysis (CAFE), for efficient calculation of 28 alignment-free dissimilarity measures. CAFE allows for both assembled genome sequences and unassembled NGS shotgun reads as input, and wraps the output in a standard PHYLIP format. In downstream analyses, CAFE can also be used to visualize the pairwise dissimilarity measures, including dendrograms, heatmap, principal coordinate analysis and network display. CAFE serves as a general k-mer based alignment-free analysis platform for studying the relationships among genomes and metagenomes, and is freely available at https://github.com/younglululu/CAFE. PMID:28472388

  7. Biophysical models of protein evolution: Understanding the patterns of evolutionary sequence divergence

    PubMed Central

    Echave, Julian; Wilke, Claus O.

    2018-01-01

    For decades, rates of protein evolution have been interpreted in terms of the vague concept of “functional importance”. Slowly evolving proteins or sites within proteins were assumed to be more functionally important and thus subject to stronger selection pressure. More recently, biophysical models of protein evolution, which combine evolutionary theory with protein biophysics, have completely revolutionized our view of the forces that shape sequence divergence. Slowly evolving proteins have been found to evolve slowly because of selection against toxic misfolding and misinteractions, linking their rate of evolution primarily to their abundance. Similarly, most slowly evolving sites in proteins are not directly involved in function, but mutating them has large impacts on protein structure and stability. Here, we review the studies of the emergent field of biophysical protein evolution that have shaped our current understanding of sequence divergence patterns. We also propose future research directions to develop this nascent field. PMID:28301766

  8. Single-virion sequencing of lamivudine-treated HBV populations reveal population evolution dynamics and demographic history.

    PubMed

    Zhu, Yuan O; Aw, Pauline P K; de Sessions, Paola Florez; Hong, Shuzhen; See, Lee Xian; Hong, Lewis Z; Wilm, Andreas; Li, Chen Hao; Hue, Stephane; Lim, Seng Gee; Nagarajan, Niranjan; Burkholder, William F; Hibberd, Martin

    2017-10-27

    Viral populations are complex, dynamic, and fast evolving. The evolution of groups of closely related viruses in a competitive environment is termed quasispecies. To fully understand the role that quasispecies play in viral evolution, characterizing the trajectories of viral genotypes in an evolving population is the key. In particular, long-range haplotype information for thousands of individual viruses is critical; yet generating this information is non-trivial. Popular deep sequencing methods generate relatively short reads that do not preserve linkage information, while third generation sequencing methods have higher error rates that make detection of low frequency mutations a bioinformatics challenge. Here we applied BAsE-Seq, an Illumina-based single-virion sequencing technology, to eight samples from four chronic hepatitis B (CHB) patients - once before antiviral treatment and once after viral rebound due to resistance. With single-virion sequencing, we obtained 248-8796 single-virion sequences per sample, which allowed us to find evidence for both hard and soft selective sweeps. We were able to reconstruct population demographic history that was independently verified by clinically collected data. We further verified four of the samples independently through PacBio SMRT and Illumina Pooled deep sequencing. Overall, we showed that single-virion sequencing yields insight into viral evolution and population dynamics in an efficient and high throughput manner. We believe that single-virion sequencing is widely applicable to the study of viral evolution in the context of drug resistance and host adaptation, allows differentiation between soft or hard selective sweeps, and may be useful in the reconstruction of intra-host viral population demographic history.

  9. In silico evolution of the Drosophila gap gene regulatory sequence under elevated mutational pressure.

    PubMed

    Chertkova, Aleksandra A; Schiffman, Joshua S; Nuzhdin, Sergey V; Kozlov, Konstantin N; Samsonova, Maria G; Gursky, Vitaly V

    2017-02-07

    Cis-regulatory sequences are often composed of many low-affinity transcription factor binding sites (TFBSs). Determining the evolutionary and functional importance of regulatory sequence composition is impeded without a detailed knowledge of the genotype-phenotype map. We simulate the evolution of regulatory sequences involved in Drosophila melanogaster embryo segmentation during early development. Natural selection evaluates gene expression dynamics produced by a computational model of the developmental network. We observe a dramatic decrease in the total number of transcription factor binding sites through the course of evolution. Despite a decrease in average sequence binding energies through time, the regulatory sequences tend towards organisations containing increased high affinity transcription factor binding sites. Additionally, the binding energies of separate sequence segments demonstrate ubiquitous mutual correlations through time. Fewer than 10% of initial TFBSs are maintained throughout the entire simulation, deemed 'core' sites. These sites have increased functional importance as assessed under wild-type conditions and their binding energy distributions are highly conserved. Furthermore, TFBSs within close proximity of core sites exhibit increased longevity, reflecting functional regulatory interactions with core sites. In response to elevated mutational pressure, evolution tends to sample regulatory sequence organisations with fewer, albeit on average, stronger functional transcription factor binding sites. These organisations are also shaped by the regulatory interactions among core binding sites with sites in their local vicinity.

  10. Conservation of tubulin-binding sequences in TRPV1 throughout evolution.

    PubMed

    Sardar, Puspendu; Kumar, Abhishek; Bhandari, Anita; Goswami, Chandan

    2012-01-01

    Transient Receptor Potential Vanilloid sub type 1 (TRPV1), commonly known as capsaicin receptor can detect multiple stimuli ranging from noxious compounds, low pH, temperature as well as electromagnetic wave at different ranges. In addition, this receptor is involved in multiple physiological and sensory processes. Therefore, functions of TRPV1 have direct influences on adaptation and further evolution also. Availability of various eukaryotic genomic sequences in public domain facilitates us in studying the molecular evolution of TRPV1 protein and the respective conservation of certain domains, motifs and interacting regions that are functionally important. Using statistical and bioinformatics tools, our analysis reveals that TRPV1 has evolved about ∼420 million years ago (MYA). Our analysis reveals that specific regions, domains and motifs of TRPV1 has gone through different selection pressure and thus have different levels of conservation. We found that among all, TRP box is the most conserved and thus have functional significance. Our results also indicate that the tubulin binding sequences (TBS) have evolutionary significance as these stretch sequences are more conserved than many other essential regions of TRPV1. The overall distribution of positively charged residues within the TBS motifs is conserved throughout evolution. In silico analysis reveals that the TBS-1 and TBS-2 of TRPV1 can form helical structures and may play important role in TRPV1 function. Our analysis identifies the regions of TRPV1, which are important for structure-function relationship. This analysis indicates that tubulin binding sequence-1 (TBS-1) near the TRP-box forms a potential helix and the tubulin interactions with TRPV1 via TBS-1 have evolutionary significance. This interaction may be required for the proper channel function and regulation and may also have significance in the context of Taxol®-induced neuropathy.

  11. Evol and ProDy for bridging protein sequence evolution and structural dynamics

    PubMed Central

    Mao, Wenzhi; Liu, Ying; Chennubhotla, Chakra; Lezon, Timothy R.; Bahar, Ivet

    2014-01-01

    Correlations between sequence evolution and structural dynamics are of utmost importance in understanding the molecular mechanisms of function and their evolution. We have integrated Evol, a new package for fast and efficient comparative analysis of evolutionary patterns and conformational dynamics, into ProDy, a computational toolbox designed for inferring protein dynamics from experimental and theoretical data. Using information-theoretic approaches, Evol coanalyzes conservation and coevolution profiles extracted from multiple sequence alignments of protein families with their inferred dynamics. Availability and implementation: ProDy and Evol are open-source and freely available under MIT License from http://prody.csb.pitt.edu/. Contact: bahar@pitt.edu PMID:24849577

  12. Concerted evolution at the population level: pupfish HindIII satellite DNA sequences.

    PubMed Central

    Elder, J F; Turner, B J

    1994-01-01

    The canonical monomers (approximately 170 bp) of an abundant (1.9 x 10(6) copies per diploid genome) satellite DNA sequence family in the genome of Cyprinodon variegatus, a "pupfish" that ranges along the Atlantic coast from Cape Cod to central Mexico, are divergent in base sequence in 10 of 12 samples collected from natural populations. The divergence involves substitutions, deletions, and insertions, is marked in scope (mean pairwise sequence similarity = 61.6%; range = 35-95.9%), is largely confined to the 3' half of the monomer, and is not correlated with the distance among collecting sites. Repetitive cloning and direct genomic sequencing experiments failed to detect intrapopulation and intraindividual variation, suggesting high levels of sequence homogeneity within populations. The satellite sequence has therefore undergone "concerted evolution," at the level of the local population. Concerted evolution has previously almost always been discussed in terms of the divergence of species or higher taxa; its intraspecific occurrence apparently has not been reported previously. The generality of the observation is difficult to evaluate, for although satellite DNAs from a large number of organisms have been studied in detail, there appear to be little or no other data on their sequence variation in natural populations. The relationship (if any) between concerted, population level, satellite DNA divergence and the extent of gene flow/genetic isolation among conspecific natural populations remains to be established. Images PMID:8302879

  13. The set of triple-resonance sequences with a multiple quantum coherence evolution period

    NASA Astrophysics Data System (ADS)

    Koźmiński, Wiktor; Zhukov, Igor

    2004-12-01

    The new pulse sequence building block that relies on evolution of heteronuclear multiple quantum coherences is proposed. The particular chemical shifts are obtained in multiple quadrature, using linear combinations of frequencies taken from spectra measured at different quantum levels. The pulse sequences designed in this way consist of small number of RF-pulses, are as short as possible, and could be applied for determination of coupling constants. The examples presented involve 2D correlations H NCO, H NCA, H N(CO) CA, and H(N) COCA via heteronuclear zero and double coherences, as well as 2D H NCOCA technique with simultaneous evolution of triple and three distinct single quantum coherences. Applications of the new sequences are presented for 13C, 15N-labeled ubiquitin.

  14. Radio Evolution of Supernova Remnants Including Nonlinear Particle Acceleration: Insights from Hydrodynamic Simulations

    NASA Astrophysics Data System (ADS)

    Pavlović, Marko Z.; Urošević, Dejan; Arbutina, Bojan; Orlando, Salvatore; Maxted, Nigel; Filipović, Miroslav D.

    2018-01-01

    We present a model for the radio evolution of supernova remnants (SNRs) obtained by using three-dimensional hydrodynamic simulations coupled with nonlinear kinetic theory of cosmic-ray (CR) acceleration in SNRs. We model the radio evolution of SNRs on a global level by performing simulations for a wide range of the relevant physical parameters, such as the ambient density, supernova (SN) explosion energy, acceleration efficiency, and magnetic field amplification (MFA) efficiency. We attribute the observed spread of radio surface brightnesses for corresponding SNR diameters to the spread of these parameters. In addition to our simulations of Type Ia SNRs, we also considered SNR radio evolution in denser, nonuniform circumstellar environments modified by the progenitor star wind. These simulations start with the mass of the ejecta substantially higher than in the case of a Type Ia SN and presumably lower shock speed. The magnetic field is understandably seen as very important for the radio evolution of SNRs. In terms of MFA, we include both resonant and nonresonant modes in our large-scale simulations by implementing models obtained from first-principles, particle-in-cell simulations and nonlinear magnetohydrodynamical simulations. We test the quality and reliability of our models on a sample consisting of Galactic and extragalactic SNRs. Our simulations give Σ ‑ D slopes between ‑4 and ‑6 for the full Sedov regime. Recent empirical slopes obtained for the Galactic samples are around ‑5, while those for the extragalactic samples are around ‑4.

  15. The accelerated build-up of the red sequence in high-redshift galaxy clusters

    NASA Astrophysics Data System (ADS)

    Cerulo, P.; Couch, W. J.; Lidman, C.; Demarco, R.; Huertas-Company, M.; Mei, S.; Sánchez-Janssen, R.; Barrientos, L. F.; Muñoz, R. P.

    2016-04-01

    We analyse the evolution of the red sequence in a sample of galaxy clusters at redshifts 0.8 < z < 1.5 taken from the HAWK-I Cluster Survey (HCS). The comparison with the low-redshift (0.04 < z < 0.08) sample of the WIde-field Nearby Galaxy-cluster Survey (WINGS) and other literature results shows that the slope and intrinsic scatter of the cluster red sequence have undergone little evolution since z = 1.5. We find that the luminous-to-faint ratio and the slope of the faint end of the luminosity distribution of the HCS red sequence are consistent with those measured in WINGS, implying that there is no deficit of red galaxies at magnitudes fainter than M_V^{ast } at high redshifts. We find that the most massive HCS clusters host a population of bright red sequence galaxies at MV < -22.0 mag, which are not observed in low-mass clusters. Interestingly, we also note the presence of a population of very bright (MV < -23.0 mag) and massive (log (M*/M⊙) > 11.5) red sequence galaxies in the WINGS clusters, which do not include only the brightest cluster galaxies and which are not present in the HCS clusters, suggesting that they formed at epochs later than z = 0.8. The comparison with the luminosity distribution of a sample of passive red sequence galaxies drawn from the COSMOS/UltraVISTA field in the photometric redshift range 0.8 < zphot < 1.5 shows that the red sequence in clusters is more developed at the faint end, suggesting that halo mass plays an important role in setting the time-scales for the build-up of the red sequence.

  16. Protein evolution analysis of S-hydroxynitrile lyase by complete sequence design utilizing the INTMSAlign software.

    PubMed

    Nakano, Shogo; Asano, Yasuhisa

    2015-02-03

    Development of software and methods for design of complete sequences of functional proteins could contribute to studies of protein engineering and protein evolution. To this end, we developed the INTMSAlign software, and used it to design functional proteins and evaluate their usefulness. The software could assign both consensus and correlation residues of target proteins. We generated three protein sequences with S-selective hydroxynitrile lyase (S-HNL) activity, which we call designed S-HNLs; these proteins folded as efficiently as the native S-HNL. Sequence and biochemical analysis of the designed S-HNLs suggested that accumulation of neutral mutations occurs during the process of S-HNLs evolution from a low-activity form to a high-activity (native) form. Taken together, our results demonstrate that our software and the associated methods could be applied not only to design of complete sequences, but also to predictions of protein evolution, especially within families such as esterases and S-HNLs.

  17. Protein evolution analysis of S-hydroxynitrile lyase by complete sequence design utilizing the INTMSAlign software

    NASA Astrophysics Data System (ADS)

    Nakano, Shogo; Asano, Yasuhisa

    2015-02-01

    Development of software and methods for design of complete sequences of functional proteins could contribute to studies of protein engineering and protein evolution. To this end, we developed the INTMSAlign software, and used it to design functional proteins and evaluate their usefulness. The software could assign both consensus and correlation residues of target proteins. We generated three protein sequences with S-selective hydroxynitrile lyase (S-HNL) activity, which we call designed S-HNLs; these proteins folded as efficiently as the native S-HNL. Sequence and biochemical analysis of the designed S-HNLs suggested that accumulation of neutral mutations occurs during the process of S-HNLs evolution from a low-activity form to a high-activity (native) form. Taken together, our results demonstrate that our software and the associated methods could be applied not only to design of complete sequences, but also to predictions of protein evolution, especially within families such as esterases and S-HNLs.

  18. Evolution of Pre-Main Sequence Accretion Disks

    NASA Technical Reports Server (NTRS)

    Hartmann, Lee W.

    2004-01-01

    The aim of this project is to develop a comprehensive global picture of the physical conditions in, and evolutionary timescales of, pre-main sequence accretion disks. The results of this work will help constrain the initial conditions for planet formation. To this end we are developing much larger samples of 3-10 Myr-old stars to provide better empirical constraints on protoplanetary disk evolution; measuring disk accretion rates in these systems; and constructing detailed model disk structures consistent with observations to infer physical conditions such as grain growth in protoplanetary disks.

  19. Evolution of Pre-Main Sequence Accretion Disks

    NASA Technical Reports Server (NTRS)

    Hartmann, Lee W.

    2003-01-01

    The aim of this project is to develop a comprehensive global picture of the physical conditions in, and evolutionary timescales of, pre-main sequence accretion disks. The results of this work will help constrain the initial conditions for planet formation. To this end we are developing much larger samples of 3-10 Myr-old stars to provide better empirical constraints on protoplanetary disk evolution; measuring disk accretion rates in these systems; and constructing detailed model disk structures consistent with observations to infer physical conditions such as grain growth in protoplanetary disks.

  20. Evolution of Pre-Main Sequence Accretion Disks

    NASA Technical Reports Server (NTRS)

    Hartmann, Lee W.

    2005-01-01

    The aim of this project was to develop a comprehensive global picture of the physical conditions in, and evolutionary timescales of, premain sequence accretion disks. The results of this work will help constrain the initial conditions for planet formation. To this end we developed much larger samples of 3-10 Myr-old stars to provide better empirical constraints on protoplanetary disk evolution; measured disk accretion rates in these systems; and constructed detailed model disk structures consistent with observations to infer physical conditions such as grain growth in protoplanetary disks.

  1. Evol and ProDy for bridging protein sequence evolution and structural dynamics.

    PubMed

    Bakan, Ahmet; Dutta, Anindita; Mao, Wenzhi; Liu, Ying; Chennubhotla, Chakra; Lezon, Timothy R; Bahar, Ivet

    2014-09-15

    Correlations between sequence evolution and structural dynamics are of utmost importance in understanding the molecular mechanisms of function and their evolution. We have integrated Evol, a new package for fast and efficient comparative analysis of evolutionary patterns and conformational dynamics, into ProDy, a computational toolbox designed for inferring protein dynamics from experimental and theoretical data. Using information-theoretic approaches, Evol coanalyzes conservation and coevolution profiles extracted from multiple sequence alignments of protein families with their inferred dynamics. ProDy and Evol are open-source and freely available under MIT License from http://prody.csb.pitt.edu/. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Clonal evolution of acute myeloid leukemia highlighted by latest genome sequencing studies.

    PubMed

    Zhang, Xuehong; Lv, Dekang; Zhang, Yu; Liu, Quentin; Li, Zhiguang

    2016-09-06

    Decades of years might be required for an initiated cell to become a fully-pledged, metastasized tumor. DNA mutations are accumulated during this process including background mutations that emerge scholastically, as well as driver mutations that selectively occur in a handful of cancer genes and confer the cell a growth advantage over its neighbors. A clone of tumor cells could be superseded by another clone that acquires new mutations and grows more aggressively. Tumor evolutional patterns have been studied for years using conventional approaches that focus on the investigation of a single or a couple of genes. Latest deep sequencing technology enables a global view of tumor evolution by deciphering almost all genome aberrations in a tumor. Tumor clones and the fate of each clone during tumor evolution can be depicted with the help of the concept of variant allele frequency. Here, we summarize the new insights of cancer evolutional progression in acute myeloid leukemia. Cancer evolution is currently thought to start from a clone that has accumulated the requisite somatically-acquired genetic aberrations through a series of increasingly disordered clinical and pathological phases, eventually leading to malignant transformation [1-3]. The observations in invasive colorectal cancer that usually emerges from an antecedent benign adenomatous polyp and in cervical cancer that proceeds through intraepithelial neoplasia support the idea of stepwise or linear cancerous progression [3-5]. Genetically, such progression is achieved by successive waves of clonal expansion during which cells acquire novel genomic alterations including single nucleotide variants (SNVs), small insertions and deletions (indels), and/or copy number variations (CNVs) [6]. The latest improvement in sequencing technology has allowed the deciphering of the whole exome or genome in different types of tumor and normal tissue pairs, providing detailed catalogue about genome aberrations during tumor

  3. Traveling wave linear accelerator with RF power flow outside of accelerating cavities

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Dolgashev, Valery A.

    A high power RF traveling wave accelerator structure includes a symmetric RF feed, an input matching cell coupled to the symmetric RF feed, a sequence of regular accelerating cavities coupled to the input matching cell at an input beam pipe end of the sequence, one or more waveguides parallel to and coupled to the sequence of regular accelerating cavities, an output matching cell coupled to the sequence of regular accelerating cavities at an output beam pipe end of the sequence, and output waveguide circuit or RF loads coupled to the output matching cell. Each of the regular accelerating cavities hasmore » a nose cone that cuts off field propagating into the beam pipe and therefore all power flows in a traveling wave along the structure in the waveguide.« less

  4. Spectrum Evolution of Accelerating or Slowing down Soliton at its Propagation in a Medium with Gold Nanorods

    NASA Astrophysics Data System (ADS)

    Trofimov, Vyacheslav A.; Lysak, Tatiana M.

    2018-04-01

    We investigate both numerically and analytically the spectrum evolution of a novel type soliton - nonlinear chirped accelerating or decelerating soliton - at a femtosecond pulse propagation in a medium containing noble nanoparticles. In our consideration, we take into account one- or two-photon absorption of laser radiation by nanorods, and time-dependent nanorod aspect ratio changing due to their melting or reshaping because of laser energy absorption. The chirped solitons are formed due to the trapping of laser radiation by the nanorods reshaping fronts, if a positive or negative phase-amplitude grating is induced by laser radiation. Accelerating or slowing down chirped soliton formation is accompanied by the soliton spectrum blue or red shift. To prove our numerical results, we derived the approximate analytical law for the spectrum maximum intensity evolution along the propagation coordinate, based on earlier developed approximate analytical solutions for accelerating and decelerating solitons.

  5. An evolution based biosensor receptor DNA sequence generation algorithm.

    PubMed

    Kim, Eungyeong; Lee, Malrey; Gatton, Thomas M; Lee, Jaewan; Zang, Yupeng

    2010-01-01

    A biosensor is composed of a bioreceptor, an associated recognition molecule, and a signal transducer that can selectively detect target substances for analysis. DNA based biosensors utilize receptor molecules that allow hybridization with the target analyte. However, most DNA biosensor research uses oligonucleotides as the target analytes and does not address the potential problems of real samples. The identification of recognition molecules suitable for real target analyte samples is an important step towards further development of DNA biosensors. This study examines the characteristics of DNA used as bioreceptors and proposes a hybrid evolution-based DNA sequence generating algorithm, based on DNA computing, to identify suitable DNA bioreceptor recognition molecules for stable hybridization with real target substances. The Traveling Salesman Problem (TSP) approach is applied in the proposed algorithm to evaluate the safety and fitness of the generated DNA sequences. This approach improves efficiency and stability for enhanced and variable-length DNA sequence generation and allows extension to generation of variable-length DNA sequences with diverse receptor recognition requirements.

  6. Neutral evolution of proteins: The superfunnel in sequence space and its relation to mutational robustness

    NASA Astrophysics Data System (ADS)

    Noirel, Josselin; Simonson, Thomas

    2008-11-01

    Following Kimura's neutral theory of molecular evolution [M. Kimura, The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983) (reprinted in 1986)], it has become common to assume that the vast majority of viable mutations of a gene confer little or no functional advantage. Yet, in silico models of protein evolution have shown that mutational robustness of sequences could be selected for, even in the context of neutral evolution. The evolution of a biological population can be seen as a diffusion on the network of viable sequences. This network is called a "neutral network." Depending on the mutation rate μ and the population size N, the biological population can evolve purely randomly (μN ≪1) or it can evolve in such a way as to select for sequences of higher mutational robustness (μN ≫1). The stringency of the selection depends not only on the product μN but also on the exact topology of the neutral network, the special arrangement of which was named "superfunnel." Even though the relation between mutation rate, population size, and selection was thoroughly investigated, a study of the salient topological features of the superfunnel that could affect the strength of the selection was wanting. This question is addressed in this study. We use two different models of proteins: on lattice and off lattice. We compare neutral networks computed using these models to random networks. From this, we identify two important factors of the topology that determine the stringency of the selection for mutationally robust sequences. First, the presence of highly connected nodes ("hubs") in the network increases the selection for mutationally robust sequences. Second, the stringency of the selection increases when the correlation between a sequence's mutational robustness and its neighbors' increases. The latter finding relates a global characteristic of the neutral network to a local one, which is attainable through experiments or molecular

  7. Neutral evolution of proteins: The superfunnel in sequence space and its relation to mutational robustness.

    PubMed

    Noirel, Josselin; Simonson, Thomas

    2008-11-14

    Following Kimura's neutral theory of molecular evolution [M. Kimura, The Neutral Theory of Molecular Evolution (Cambridge University Press, Cambridge, 1983) (reprinted in 1986)], it has become common to assume that the vast majority of viable mutations of a gene confer little or no functional advantage. Yet, in silico models of protein evolution have shown that mutational robustness of sequences could be selected for, even in the context of neutral evolution. The evolution of a biological population can be seen as a diffusion on the network of viable sequences. This network is called a "neutral network." Depending on the mutation rate mu and the population size N, the biological population can evolve purely randomly (muN<1) or it can evolve in such a way as to select for sequences of higher mutational robustness (muN>1). The stringency of the selection depends not only on the product muN but also on the exact topology of the neutral network, the special arrangement of which was named "superfunnel." Even though the relation between mutation rate, population size, and selection was thoroughly investigated, a study of the salient topological features of the superfunnel that could affect the strength of the selection was wanting. This question is addressed in this study. We use two different models of proteins: on lattice and off lattice. We compare neutral networks computed using these models to random networks. From this, we identify two important factors of the topology that determine the stringency of the selection for mutationally robust sequences. First, the presence of highly connected nodes ("hubs") in the network increases the selection for mutationally robust sequences. Second, the stringency of the selection increases when the correlation between a sequence's mutational robustness and its neighbors' increases. The latter finding relates a global characteristic of the neutral network to a local one, which is attainable through experiments or molecular

  8. Complete chloroplast and ribosomal sequences for 30 accessions elucidate evolution of Oryza AA genome species

    PubMed Central

    Kim, Kyunghee; Lee, Sang-Choon; Lee, Junki; Yu, Yeisoo; Yang, Kiwoung; Choi, Beom-Soon; Koh, Hee-Jong; Waminal, Nomar Espinosa; Choi, Hong-Il; Kim, Nam-Hoon; Jang, Woojong; Park, Hyun-Seung; Lee, Jonghoon; Lee, Hyun Oh; Joh, Ho Jun; Lee, Hyeon Ju; Park, Jee Young; Perumal, Sampath; Jayakodi, Murukarthick; Lee, Yun Sun; Kim, Backki; Copetti, Dario; Kim, Soonok; Kim, Sunggil; Lim, Ki-Byung; Kim, Young-Dong; Lee, Jungho; Cho, Kwang-Su; Park, Beom-Seok; Wing, Rod A.; Yang, Tae-Jin

    2015-01-01

    Cytoplasmic chloroplast (cp) genomes and nuclear ribosomal DNA (nR) are the primary sequences used to understand plant diversity and evolution. We introduce a high-throughput method to simultaneously obtain complete cp and nR sequences using Illumina platform whole-genome sequence. We applied the method to 30 rice specimens belonging to nine Oryza species. Concurrent phylogenomic analysis using cp and nR of several of specimens of the same Oryza AA genome species provides insight into the evolution and domestication of cultivated rice, clarifying three ambiguous but important issues in the evolution of wild Oryza species. First, cp-based trees clearly classify each lineage but can be biased by inter-subspecies cross-hybridization events during speciation. Second, O. glumaepatula, a South American wild rice, includes two cytoplasm types, one of which is derived from a recent interspecies hybridization with O. longistminata. Third, the Australian O. rufipogan-type rice is a perennial form of O. meridionalis. PMID:26506948

  9. Repetitive sequences and epigenetic modification: inseparable partners play important roles in the evolution of plant sex chromosomes.

    PubMed

    Li, Shu-Fen; Zhang, Guo-Jun; Yuan, Jin-Hong; Deng, Chuan-Liang; Gao, Wu-Jun

    2016-05-01

    The present review discusses the roles of repetitive sequences played in plant sex chromosome evolution, and highlights epigenetic modification as potential mechanism of repetitive sequences involved in sex chromosome evolution. Sex determination in plants is mostly based on sex chromosomes. Classic theory proposes that sex chromosomes evolve from a specific pair of autosomes with emergence of a sex-determining gene(s). Subsequently, the newly formed sex chromosomes stop recombination in a small region around the sex-determining locus, and over time, the non-recombining region expands to almost all parts of the sex chromosomes. Accumulation of repetitive sequences, mostly transposable elements and tandem repeats, is a conspicuous feature of the non-recombining region of the Y chromosome, even in primitive one. Repetitive sequences may play multiple roles in sex chromosome evolution, such as triggering heterochromatization and causing recombination suppression, leading to structural and morphological differentiation of sex chromosomes, and promoting Y chromosome degeneration and X chromosome dosage compensation. In this article, we review the current status of this field, and based on preliminary evidence, we posit that repetitive sequences are involved in sex chromosome evolution probably via epigenetic modification, such as DNA and histone methylation, with small interfering RNAs as the mediator.

  10. Genome sequence analysis of the model grass Brachypodium distachyon: insights into grass genome evolution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schulman, Al

    2009-08-09

    Three subfamilies of grasses, the Erhardtoideae (rice), the Panicoideae (maize, sorghum, sugar cane and millet), and the Pooideae (wheat, barley and cool season forage grasses) provide the basis of human nutrition and are poised to become major sources of renewable energy. Here we describe the complete genome sequence of the wild grass Brachypodium distachyon (Brachypodium), the first member of the Pooideae subfamily to be completely sequenced. Comparison of the Brachypodium, rice and sorghum genomes reveals a precise sequence- based history of genome evolution across a broad diversity of the grass family and identifies nested insertions of whole chromosomes into centromericmore » regions as a predominant mechanism driving chromosome evolution in the grasses. The relatively compact genome of Brachypodium is maintained by a balance of retroelement replication and loss. The complete genome sequence of Brachypodium, coupled to its exceptional promise as a model system for grass research, will support the development of new energy and food crops« less

  11. From protostellar to pre-main-sequence evolution

    NASA Astrophysics Data System (ADS)

    D'Antona, F.

    I summarize the status of pre-main-sequence evolutionary tracks starting from the first steps dating back to the concept of Hayashi track. Understanding of the dynamical protostellar phase in the vision of Palla & Stahler, who introduced the concept of the deuterium burning thermostat and of stellar birthline, provided for a long time a link between the dynamical and hydrostatic evolution. Disk accretion however changed considerably the view, but re-introducing some ambiguities which must still be solved. The limitations and uncertainties in the mass and age determination from models for young stellar objects are summarized, but the burning of light elements is still a powerful observational signature.

  12. GPU-Acceleration of Sequence Homology Searches with Database Subsequence Clustering.

    PubMed

    Suzuki, Shuji; Kakuta, Masanori; Ishida, Takashi; Akiyama, Yutaka

    2016-01-01

    Sequence homology searches are used in various fields and require large amounts of computation time, especially for metagenomic analysis, owing to the large number of queries and the database size. To accelerate computing analyses, graphics processing units (GPUs) are widely used as a low-cost, high-performance computing platform. Therefore, we mapped the time-consuming steps involved in GHOSTZ, which is a state-of-the-art homology search algorithm for protein sequences, onto a GPU and implemented it as GHOSTZ-GPU. In addition, we optimized memory access for GPU calculations and for communication between the CPU and GPU. As per results of the evaluation test involving metagenomic data, GHOSTZ-GPU with 12 CPU threads and 1 GPU was approximately 3.0- to 4.1-fold faster than GHOSTZ with 12 CPU threads. Moreover, GHOSTZ-GPU with 12 CPU threads and 3 GPUs was approximately 5.8- to 7.7-fold faster than GHOSTZ with 12 CPU threads.

  13. GPU-Acceleration of Sequence Homology Searches with Database Subsequence Clustering

    PubMed Central

    Suzuki, Shuji; Kakuta, Masanori; Ishida, Takashi; Akiyama, Yutaka

    2016-01-01

    Sequence homology searches are used in various fields and require large amounts of computation time, especially for metagenomic analysis, owing to the large number of queries and the database size. To accelerate computing analyses, graphics processing units (GPUs) are widely used as a low-cost, high-performance computing platform. Therefore, we mapped the time-consuming steps involved in GHOSTZ, which is a state-of-the-art homology search algorithm for protein sequences, onto a GPU and implemented it as GHOSTZ-GPU. In addition, we optimized memory access for GPU calculations and for communication between the CPU and GPU. As per results of the evaluation test involving metagenomic data, GHOSTZ-GPU with 12 CPU threads and 1 GPU was approximately 3.0- to 4.1-fold faster than GHOSTZ with 12 CPU threads. Moreover, GHOSTZ-GPU with 12 CPU threads and 3 GPUs was approximately 5.8- to 7.7-fold faster than GHOSTZ with 12 CPU threads. PMID:27482905

  14. Sequence diversity and evolution of antimicrobial peptides in invertebrates.

    PubMed

    Tassanakajon, Anchalee; Somboonwiwat, Kunlaya; Amparyup, Piti

    2015-02-01

    Antimicrobial peptides (AMPs) are evolutionarily ancient molecules that act as the key components in the invertebrate innate immunity against invading pathogens. Several AMPs have been identified and characterized in invertebrates, and found to display considerable diversity in their amino acid sequence, structure and biological activity. AMP genes appear to have rapidly evolved, which might have arisen from the co-evolutionary arms race between host and pathogens, and enabled organisms to survive in different microbial environments. Here, the sequence diversity of invertebrate AMPs (defensins, cecropins, crustins and anti-lipopolysaccharide factors) are presented to provide a better understanding of the evolution pattern of these peptides that play a major role in host defense mechanisms. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Pre-main Sequence Evolution and the Hydrogen-Burning Minimum Mass

    NASA Astrophysics Data System (ADS)

    Nakano, Takenori

    There is a lower limit to the mass of the main-sequence stars (the hydrogen-burning minimum mass) below which the stars cannot replenish the energy lost from their surfaces with the energy released by the hydrogen burning in their cores. This is caused by the electron degeneracy in the stars which suppresses the increase of the central temperature with contraction. To find out the lower limit we need the accurate knowledge of the pre-main sequence evolution of very low-mass stars in which the effect of electron degeneracy is important. We review how Hayashi and Nakano (1963) carried out the first determination of this limit.

  16. Acceleration and evolution of a hollow electron beam in wakefields driven by a Laguerre-Gaussian laser pulse

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Guo-Bo; College of Science, National University of Defense Technology, Changsha 410073; Chen, Min, E-mail: minchen@sjtu.edu.cn, E-mail: yanyunma@126.com

    2016-03-15

    We show that a ring-shaped hollow electron beam can be injected and accelerated by using a Laguerre-Gaussian laser pulse and ionization-induced injection in a laser wakefield accelerator. The acceleration and evolution of such a hollow, relativistic electron beam are investigated through three-dimensional particle-in-cell simulations. We find that both the ring size and the beam thickness oscillate during the acceleration. The beam azimuthal shape is angularly dependent and evolves during the acceleration. The beam ellipticity changes resulting from the electron angular momenta obtained from the drive laser pulse and the focusing forces from the wakefield. The dependence of beam ring radiusmore » on the laser-plasma parameters (e.g., laser intensity, focal size, and plasma density) is studied. Such a hollow electron beam may have potential applications for accelerating and collimating positively charged particles.« less

  17. Effects of Main-Sequence Mass Loss on Stellar and Galactic Chemical Evolution.

    NASA Astrophysics Data System (ADS)

    Guzik, Joyce Ann

    1988-06-01

    L. A. Willson, G. H. Bowen and C. Struck -Marcell have proposed that 1 to 3 solar mass stars may experience evolutionarily significant mass loss during the early part of their main-sequence phase. The suggested mass-loss mechanism is pulsation, facilitated by rapid rotation. Initial mass-loss rates may be as large as several times 10^{-9}M o/yr, diminishing over several times 10^8 years. We attempted to test this hypothesis by comparing some theoretical implications with observations. Three areas are addressed: Solar models, cluster HR diagrams, and galactic chemical evolution. Mass-losing solar models were evolved that match the Sun's luminosity and radius at its present age. The most extreme viable models have initial mass 2.0 M o, and mass-loss rates decreasing exponentially over 2-3 times 10^8 years. Compared to a constant -mass model, these models require a reduced initial ^4He abundance, have deeper envelope convection zones and higher ^8B neutrino fluxes. Early processing of present surface layers at higher interior temperatures increases the surface ^3He abundance, destroys Li, Be and B, and decreases the surface C/N ratio following first dredge-up. Evolution calculations incorporating main-sequence mass loss were completed for a grid of models with initial masses 1.25 to 2.0 Mo and mass loss timescales 0.2 to 2.0 Gyr. Cluster HR diagrams synthesized with these models confirm the potential for the hypothesis to explain observed spreads or bifurcations in the upper main sequence, blue stragglers, anomalous giants, and poor fits of main-sequence turnoffs by standard isochrones. Simple closed galactic chemical evolution models were used to test the effects of main-sequence mass loss on the F and G dwarf distribution. Stars between 3.0 M o and a metallicity -dependent lower mass are assumed to lose mass. The models produce a 30 to 60% increase in the stars to stars-plus -remnants ratio, with fewer early-F dwarfs and many more late-F dwarfs remaining on the main

  18. Evolution of Pre-Main Sequence Accretion Disks

    NASA Technical Reports Server (NTRS)

    Hartmann, Lee W.

    2000-01-01

    The aim of this project was to develop a comprehensive global picture of the physical conditions in, and evolutionary timescales of, pre-main sequence accretion disks. The results of this work will help constrain the initial conditions for planet formation. To this end we: (1) Developed detailed calculations of disk structure to study physical conditions and investigate the observational effects of grain growth in T Tauri disks; (2) Studied the dusty emission and accretion rates in older disk systems, with ages closer to the expected epoch of (giant) planet formation at 3-10 Myr, and (3) Began a project to develop much larger samples of 3-10 Myr-old stars to provide better empirical constraints on protoplanetary disk evolution.

  19. Analyzing radial acceleration with a smartphone acceleration sensor

    NASA Astrophysics Data System (ADS)

    Vogt, Patrik; Kuhn, Jochen

    2013-03-01

    This paper continues the sequence of experiments using the acceleration sensor of smartphones (for description of the function and the use of the acceleration sensor, see Ref. 1) within this column, in this case for analyzing the radial acceleration.

  20. Modeling the expected lifetime and evolution of a deme's principal genetic sequence.

    NASA Astrophysics Data System (ADS)

    Clark, Brian

    2014-03-01

    The principal genetic sequence (PGS) is the most common genetic sequence in a deme. The PGS changes over time because new genetic sequences are created by inversions, compete with the current PGS, and a small fraction become PGSs. A set of coupled difference equations provides a description of the evolution of the PGS distribution function in an ensemble of demes. Solving the set of equations produces the survival probability of a new genetic sequence and the expected lifetime of an existing PGS as a function of inversion size and rate, recombination rate, and deme size. Additionally, the PGS distribution function is used to explain the transition pathway from old to new PGSs. We compare these results to a cellular automaton based representation of a deme and the drosophila species, D. melanogaster and D. yakuba.

  1. Genome sequencing of the extinct Eurasian wild aurochs illuminates the phylogeography and evolution of cattle

    USDA-ARS?s Scientific Manuscript database

    Interrogation of modern and ancient bovine genome sequences provides a valuable model to study the evolution of cattle. Here, we analyse the first complete wild aurochs (Bos primigenius) genome sequence using DNA extracted from a ~ 6,750 year-old humerus bone retrieved from a cave site in Derbyshire...

  2. The pig X and Y Chromosomes: structure, sequence, and evolution

    PubMed Central

    Skinner, Benjamin M.; Sargent, Carole A.; Churcher, Carol; Hunt, Toby; Herrero, Javier; Loveland, Jane E.; Dunn, Matt; Louzada, Sandra; Fu, Beiyuan; Chow, William; Gilbert, James; Austin-Guest, Siobhan; Beal, Kathryn; Carvalho-Silva, Denise; Cheng, William; Gordon, Daria; Grafham, Darren; Hardy, Matt; Harley, Jo; Hauser, Heidi; Howden, Philip; Howe, Kerstin; Lachani, Kim; Ellis, Peter J.I.; Kelly, Daniel; Kerry, Giselle; Kerwin, James; Ng, Bee Ling; Threadgold, Glen; Wileman, Thomas; Wood, Jonathan M.D.; Yang, Fengtang; Harrow, Jen; Affara, Nabeel A.; Tyler-Smith, Chris

    2016-01-01

    We have generated an improved assembly and gene annotation of the pig X Chromosome, and a first draft assembly of the pig Y Chromosome, by sequencing BAC and fosmid clones from Duroc animals and incorporating information from optical mapping and fiber-FISH. The X Chromosome carries 1033 annotated genes, 690 of which are protein coding. Gene order closely matches that found in primates (including humans) and carnivores (including cats and dogs), which is inferred to be ancestral. Nevertheless, several protein-coding genes present on the human X Chromosome were absent from the pig, and 38 pig-specific X-chromosomal genes were annotated, 22 of which were olfactory receptors. The pig Y-specific Chromosome sequence generated here comprises 30 megabases (Mb). A 15-Mb subset of this sequence was assembled, revealing two clusters of male-specific low copy number genes, separated by an ampliconic region including the HSFY gene family, which together make up most of the short arm. Both clusters contain palindromes with high sequence identity, presumably maintained by gene conversion. Many of the ancestral X-related genes previously reported in at least one mammalian Y Chromosome are represented either as active genes or partial sequences. This sequencing project has allowed us to identify genes—both single copy and amplified—on the pig Y Chromosome, to compare the pig X and Y Chromosomes for homologous sequences, and thereby to reveal mechanisms underlying pig X and Y Chromosome evolution. PMID:26560630

  3. Acceleration modules in linear induction accelerators

    NASA Astrophysics Data System (ADS)

    Wang, Shao-Heng; Deng, Jian-Jun

    2014-05-01

    The Linear Induction Accelerator (LIA) is a unique type of accelerator that is capable of accelerating kilo-Ampere charged particle current to tens of MeV energy. The present development of LIA in MHz bursting mode and the successful application into a synchrotron have broadened LIA's usage scope. Although the transformer model is widely used to explain the acceleration mechanism of LIAs, it is not appropriate to consider the induction electric field as the field which accelerates charged particles for many modern LIAs. We have examined the transition of the magnetic cores' functions during the LIA acceleration modules' evolution, distinguished transformer type and transmission line type LIA acceleration modules, and re-considered several related issues based on transmission line type LIA acceleration module. This clarified understanding should help in the further development and design of LIA acceleration modules.

  4. Evolution of Pre-Main Sequence Accretion Disks

    NASA Technical Reports Server (NTRS)

    Hartmann, Lee W.

    2002-01-01

    The aim of this project is to develop a comprehensive global picture of the physical conditions in, and evolutionary timescales of, pre-main sequence accretion disks. The results of this work will help constrain the initial conditions for planet formation. To this end we plan to: (1) Develop much larger samples of 3-10 Myr-old stars to provide better empirical constraints on protoplanetary disk evolution; (2) Study the dusty emission and accretion rates in these systems, with ages closer to the expected epoch of (giant) planet formation at 3-10 Myr; and (3) Develop detailed model disk structures consistent with observations to infer physical conditions in protoplanetary disks and to constrain possible grain growth as the first stage of planetesimal formation.

  5. Evolution of endogenous sequences of banana streak virus: what can we learn from banana (Musa sp.) evolution?

    PubMed

    Gayral, Philippe; Blondin, Laurence; Guidolin, Olivier; Carreel, Françoise; Hippolyte, Isabelle; Perrier, Xavier; Iskra-Caruana, Marie-Line

    2010-07-01

    Endogenous plant pararetroviruses (EPRVs) are viral sequences of the family Caulimoviridae integrated into the nuclear genome of numerous plant species. The ability of some endogenous sequences of Banana streak viruses (eBSVs) in the genome of banana (Musa sp.) to induce infections just like the virus itself was recently demonstrated (P. Gayral et al., J. Virol. 83:6697-6710, 2008). Although eBSVs probably arose from accidental events, infectious eBSVs constitute an extreme case of parasitism, as well as a newly described strategy for vertical virus transmission in plants. We investigated the early evolutionary stages of infectious eBSV for two distinct BSV species-GF (BSGFV) and Imové (BSImV)-through the study of their distribution, insertion polymorphism, and structure evolution among selected banana genotypes representative of the diversity of 60 wild Musa species and genotypes. To do so, the historical frame of host evolution was analyzed by inferring banana phylogeny from two chloroplast regions-matK and trnL-trnF-as well as from the nuclear genome, using 19 microsatellite loci. We demonstrated that both BSV species integrated recently in banana evolution, circa 640,000 years ago. The two infectious eBSVs were subjected to different selective pressures and showed distinct levels of rearrangement within their final structure. In addition, the molecular phylogenies of integrated and nonintegrated BSVs enabled us to establish the phylogenetic origins of eBSGFV and eBSImV.

  6. Structure and evolution of cereal genomes.

    PubMed

    Paterson, Andrew H; Bowers, John E; Peterson, Daniel G; Estill, James C; Chapman, Brad A

    2003-12-01

    The cereal species, of central importance to our diet, began to diverge 50-70 million years ago. For the past few thousand years, these species have undergone largely parallel selection regimes associated with domestication and improvement. The rice genome sequence provides a platform for organizing information about diverse cereals, and together with genetic maps and sequence samples from other cereals is yielding new insights into both the shared and the independent dimensions of cereal evolution. New data and population-based approaches are identifying genes that have been involved in cereal improvement. Reduced-representation sequencing promises to accelerate gene discovery in many large-genome cereals, and to better link the under-explored genomes of 'orphan' cereals with state-of-the-art knowledge.

  7. Temporal evolution of the electric field accelerating electrons away from the auroral ionosphere.

    PubMed

    Marklund, G T; Ivchenko, N; Karlsson, T; Fazakerley, A; Dunlop, M; Lindqvist, P A; Buchert, S; Owen, C; Taylor, M; Vaivalds, A; Carter, P; André, M; Balogh, A

    2001-12-13

    The bright night-time aurorae that are visible to the unaided eye are caused by electrons accelerated towards Earth by an upward-pointing electric field. On adjacent geomagnetic field lines the reverse process occurs: a downward-pointing electric field accelerates electrons away from Earth. Such magnetic-field-aligned electric fields in the collisionless plasma above the auroral ionosphere have been predicted, but how they could be maintained is still a matter for debate. The spatial and temporal behaviour of the electric fields-a knowledge of which is crucial to an understanding of their nature-cannot be resolved uniquely by single satellite measurements. Here we report on the first observations by a formation of identically instrumented satellites crossing a beam of upward-accelerated electrons. The structure of the electric potential accelerating the beam grew in magnitude and width for about 200 s, accompanied by a widening of the downward-current sheet, with the total current remaining constant. The 200-s timescale suggests that the evacuation of the electrons from the ionosphere contributes to the formation of the downward-pointing magnetic-field-aligned electric fields. This evolution implies a growing load in the downward leg of the current circuit, which may affect the visible discrete aurorae.

  8. Advances in understanding tumour evolution through single-cell sequencing.

    PubMed

    Kuipers, Jack; Jahn, Katharina; Beerenwinkel, Niko

    2017-04-01

    The mutational heterogeneity observed within tumours poses additional challenges to the development of effective cancer treatments. A thorough understanding of a tumour's subclonal composition and its mutational history is essential to open up the design of treatments tailored to individual patients. Comparative studies on a large number of tumours permit the identification of mutational patterns which may refine forecasts of cancer progression, response to treatment and metastatic potential. The composition of tumours is shaped by evolutionary processes. Recent advances in next-generation sequencing offer the possibility to analyse the evolutionary history and accompanying heterogeneity of tumours at an unprecedented resolution, by sequencing single cells. New computational challenges arise when moving from bulk to single-cell sequencing data, leading to the development of novel modelling frameworks. In this review, we present the state of the art methods for understanding the phylogeny encoded in bulk or single-cell sequencing data, and highlight future directions for developing more comprehensive and informative pictures of tumour evolution. This article is part of a Special Issue entitled: Evolutionary principles - heterogeneity in cancer?, edited by Dr. Robert A. Gatenby. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  9. Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development

    PubMed Central

    2011-01-01

    Background We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. Results The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. Conclusions Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution. PMID:21854559

  10. Genome sequence of an Australian kangaroo, Macropus eugenii, provides insight into the evolution of mammalian reproduction and development.

    PubMed

    Renfree, Marilyn B; Papenfuss, Anthony T; Deakin, Janine E; Lindsay, James; Heider, Thomas; Belov, Katherine; Rens, Willem; Waters, Paul D; Pharo, Elizabeth A; Shaw, Geoff; Wong, Emily S W; Lefèvre, Christophe M; Nicholas, Kevin R; Kuroki, Yoko; Wakefield, Matthew J; Zenger, Kyall R; Wang, Chenwei; Ferguson-Smith, Malcolm; Nicholas, Frank W; Hickford, Danielle; Yu, Hongshi; Short, Kirsty R; Siddle, Hannah V; Frankenberg, Stephen R; Chew, Keng Yih; Menzies, Brandon R; Stringer, Jessica M; Suzuki, Shunsuke; Hore, Timothy A; Delbridge, Margaret L; Patel, Hardip R; Mohammadi, Amir; Schneider, Nanette Y; Hu, Yanqiu; O'Hara, William; Al Nadaf, Shafagh; Wu, Chen; Feng, Zhi-Ping; Cocks, Benjamin G; Wang, Jianghui; Flicek, Paul; Searle, Stephen M J; Fairley, Susan; Beal, Kathryn; Herrero, Javier; Carone, Dawn M; Suzuki, Yutaka; Sugano, Sumio; Toyoda, Atsushi; Sakaki, Yoshiyuki; Kondo, Shinji; Nishida, Yuichiro; Tatsumoto, Shoji; Mandiou, Ion; Hsu, Arthur; McColl, Kaighin A; Lansdell, Benjamin; Weinstock, George; Kuczek, Elizabeth; McGrath, Annette; Wilson, Peter; Men, Artem; Hazar-Rethinam, Mehlika; Hall, Allison; Davis, John; Wood, David; Williams, Sarah; Sundaravadanam, Yogi; Muzny, Donna M; Jhangiani, Shalini N; Lewis, Lora R; Morgan, Margaret B; Okwuonu, Geoffrey O; Ruiz, San Juana; Santibanez, Jireh; Nazareth, Lynne; Cree, Andrew; Fowler, Gerald; Kovar, Christie L; Dinh, Huyen H; Joshi, Vandita; Jing, Chyn; Lara, Fremiet; Thornton, Rebecca; Chen, Lei; Deng, Jixin; Liu, Yue; Shen, Joshua Y; Song, Xing-Zhi; Edson, Janette; Troon, Carmen; Thomas, Daniel; Stephens, Amber; Yapa, Lankesha; Levchenko, Tanya; Gibbs, Richard A; Cooper, Desmond W; Speed, Terence P; Fujiyama, Asao; Graves, Jennifer A M; O'Neill, Rachel J; Pask, Andrew J; Forrest, Susan M; Worley, Kim C

    2011-08-29

    We present the genome sequence of the tammar wallaby, Macropus eugenii, which is a member of the kangaroo family and the first representative of the iconic hopping mammals that symbolize Australia to be sequenced. The tammar has many unusual biological characteristics, including the longest period of embryonic diapause of any mammal, extremely synchronized seasonal breeding and prolonged and sophisticated lactation within a well-defined pouch. Like other marsupials, it gives birth to highly altricial young, and has a small number of very large chromosomes, making it a valuable model for genomics, reproduction and development. The genome has been sequenced to 2 × coverage using Sanger sequencing, enhanced with additional next generation sequencing and the integration of extensive physical and linkage maps to build the genome assembly. We also sequenced the tammar transcriptome across many tissues and developmental time points. Our analyses of these data shed light on mammalian reproduction, development and genome evolution: there is innovation in reproductive and lactational genes, rapid evolution of germ cell genes, and incomplete, locus-specific X inactivation. We also observe novel retrotransposons and a highly rearranged major histocompatibility complex, with many class I genes located outside the complex. Novel microRNAs in the tammar HOX clusters uncover new potential mammalian HOX regulatory elements. Analyses of these resources enhance our understanding of marsupial gene evolution, identify marsupial-specific conserved non-coding elements and critical genes across a range of biological systems, including reproduction, development and immunity, and provide new insight into marsupial and mammalian biology and genome evolution.

  11. Population genetics and molecular evolution of DNA sequences in transposable elements. I. A simulation framework.

    PubMed

    Kijima, T E; Innan, Hideki

    2013-11-01

    A population genetic simulation framework is developed to understand the behavior and molecular evolution of DNA sequences of transposable elements. Our model incorporates random transposition and excision of transposable element (TE) copies, two modes of selection against TEs, and degeneration of transpositional activity by point mutations. We first investigated the relationships between the behavior of the copy number of TEs and these parameters. Our results show that when selection is weak, the genome can maintain a relatively large number of TEs, but most of them are less active. In contrast, with strong selection, the genome can maintain only a limited number of TEs but the proportion of active copies is large. In such a case, there could be substantial fluctuations of the copy number over generations. We also explored how DNA sequences of TEs evolve through the simulations. In general, active copies form clusters around the original sequence, while less active copies have long branches specific to themselves, exhibiting a star-shaped phylogeny. It is demonstrated that the phylogeny of TE sequences could be informative to understand the dynamics of TE evolution.

  12. Limits of neutral drift: lessons from the in vitro evolution of two ribozymes.

    PubMed

    Petrie, Katherine L; Joyce, Gerald F

    2014-10-01

    The relative contributions of adaptive selection and neutral drift to genetic change are unknown but likely depend on the inherent abundance of functional genotypes in sequence space and how accessible those genotypes are to one another. To better understand the relative roles of selection and drift in evolution, local fitness landscapes for two different RNA ligase ribozymes were examined using a continuous in vitro evolution system under conditions that foster the capacity for neutral drift to mediate genetic change. The exploration of sequence space was accelerated by increasing the mutation rate using mutagenic nucleotide analogs. Drift was encouraged by carrying out evolution within millions of separate compartments to exploit the founder effect. Deep sequencing of individuals from the evolved populations revealed that the distribution of genotypes did not escape the starting local fitness peak, remaining clustered around the sequence used to initiate evolution. This is consistent with a fitness landscape where high-fitness genotypes are sparse and well isolated, and suggests, at least in this context, that neutral drift alone is not a primary driver of genetic change. Neutral drift does, however, provide a repository of genetic variation upon which adaptive selection can act.

  13. Fossil rhabdoviral sequences integrated into arthropod genomes: ontogeny, evolution, and potential functionality.

    PubMed

    Fort, Philippe; Albertini, Aurélie; Van-Hua, Aurélie; Berthomieu, Arnaud; Roche, Stéphane; Delsuc, Frédéric; Pasteur, Nicole; Capy, Pierre; Gaudin, Yves; Weill, Mylène

    2012-01-01

    Retroelements represent a considerable fraction of many eukaryotic genomes and are considered major drives for adaptive genetic innovations. Recent discoveries showed that despite not normally using DNA intermediates like retroviruses do, Mononegaviruses (i.e., viruses with nonsegmented, negative-sense RNA genomes) can integrate gene fragments into the genomes of their hosts. This was shown for Bornaviridae and Filoviridae, the sequences of which have been found integrated into the germ line cells of many vertebrate hosts. Here, we show that Rhabdoviridae sequences, the major Mononegavirales family, have integrated only into the genomes of arthropod species. We identified 185 integrated rhabdoviral elements (IREs) coding for nucleoproteins, glycoproteins, or RNA-dependent RNA polymerases; they were mostly found in the genomes of the mosquito Aedes aegypti and the blacklegged tick Ixodes scapularis. Phylogenetic analyses showed that most IREs in A. aegypti derived from multiple independent integration events. Since RNA viruses are submitted to much higher substitution rates as compared with their hosts, IREs thus represent fossil traces of the diversity of extinct Rhabdoviruses. Furthermore, analyses of orthologous IREs in A. aegypti field mosquitoes sampled worldwide identified an integrated polymerase IRE fragment that appeared under purifying selection within several million years, which supports a functional role in the host's biology. These results show that A. aegypti was subjected to repeated Rhabdovirus infectious episodes during its evolution history, which led to the accumulation of many integrated sequences. They also suggest that like retroviruses, integrated rhabdoviral sequences may participate actively in the evolution of their hosts.

  14. Numerical Simulation of Stress evolution and earthquake sequence of the Tibetan Plateau

    NASA Astrophysics Data System (ADS)

    Dong, Peiyu; Hu, Caibo; Shi, Yaolin

    2015-04-01

    The India-Eurasia's collision produces N-S compression and results in large thrust fault in the southern edge of the Tibetan Plateau. Differential eastern flow of the lower crust of the plateau leads to large strike-slip faults and normal faults within the plateau. From 1904 to 2014, more than 30 earthquakes of Mw > 6.5 occurred sequentially in this distinctive tectonic environment. How did the stresses evolve during the last 110 years, how did the earthquakes interact with each other? Can this knowledge help us to forecast the future seismic hazards? In this essay, we tried to simulate the evolution of the stress field and the earthquake sequence in the Tibetan plateau within the last 110 years with a 2-D finite element model. Given an initial state of stress, the boundary condition was constrained by the present-day GPS observation, which was assumed as a constant rate during the 110 years. We calculated stress evolution year by year, and earthquake would occur if stress exceed the crustal strength. Stress changes due to each large earthquake in the sequence was calculated and contributed to the stress evolution. A key issue is the choice of initial stress state of the modeling, which is actually unknown. Usually, in the study of earthquake triggering, people assume the initial stress is zero, and only calculate the stress changes by large earthquakes - the Coulomb failure stress changes (Δ CFS). To some extent, this simplified method is a powerful tool because it can reveal which fault or which part of a fault becomes more risky or safer relatively. Nonetheless, it has not utilized all information available to us. The earthquake sequence reveals, though far from complete, some information about the stress state in the region. If the entire region is close to a self-organized critical or subcritical state, earthquake stress drop provides an estimate of lower limit of initial state. For locations no earthquakes occurred during the period, initial stress has to be

  15. Genome sequence diversity and clues to the evolution of variola (smallpox) virus.

    PubMed

    Esposito, Joseph J; Sammons, Scott A; Frace, A Michael; Osborne, John D; Olsen-Rasmussen, Melissa; Zhang, Ming; Govil, Dhwani; Damon, Inger K; Kline, Richard; Laker, Miriam; Li, Yu; Smith, Geoffrey L; Meyer, Hermann; Leduc, James W; Wohlhueter, Robert M

    2006-08-11

    Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.

  16. Real-time image sequence segmentation using curve evolution

    NASA Astrophysics Data System (ADS)

    Zhang, Jun; Liu, Weisong

    2001-04-01

    In this paper, we describe a novel approach to image sequence segmentation and its real-time implementation. This approach uses the 3D structure tensor to produce a more robust frame difference signal and uses curve evolution to extract whole objects. Our algorithm is implemented on a standard PC running the Windows operating system with video capture from a USB camera that is a standard Windows video capture device. Using the Windows standard video I/O functionalities, our segmentation software is highly portable and easy to maintain and upgrade. In its current implementation on a Pentium 400, the system can perform segmentation at 5 frames/sec with a frame resolution of 160 by 120.

  17. The Complete Chloroplast and Mitochondrial Genome Sequences of Boea hygrometrica: Insights into the Evolution of Plant Organellar Genomes

    PubMed Central

    Wang, Xumin; Deng, Xin; Zhang, Xiaowei; Hu, Songnian; Yu, Jun

    2012-01-01

    The complete nucleotide sequences of the chloroplast (cp) and mitochondrial (mt) genomes of resurrection plant Boea hygrometrica (Bh, Gesneriaceae) have been determined with the lengths of 153,493 bp and 510,519 bp, respectively. The smaller chloroplast genome contains more genes (147) with a 72% coding sequence, and the larger mitochondrial genome have less genes (65) with a coding faction of 12%. Similar to other seed plants, the Bh cp genome has a typical quadripartite organization with a conserved gene in each region. The Bh mt genome has three recombinant sequence repeats of 222 bp, 843 bp, and 1474 bp in length, which divide the genome into a single master circle (MC) and four isomeric molecules. Compared to other angiosperms, one remarkable feature of the Bh mt genome is the frequent transfer of genetic material from the cp genome during recent Bh evolution. We also analyzed organellar genome evolution in general regarding genome features as well as compositional dynamics of sequence and gene structure/organization, providing clues for the understanding of the evolution of organellar genomes in plants. The cp-derived sequences including tRNAs found in angiosperm mt genomes support the conclusion that frequent gene transfer events may have begun early in the land plant lineage. PMID:22291979

  18. Emergence and Evolution of Hominidae-Specific Coding and Noncoding Genomic Sequences.

    PubMed

    Saber, Morteza Mahmoudi; Adeyemi Babarinde, Isaac; Hettiarachchi, Nilmini; Saitou, Naruya

    2016-07-12

    Family Hominidae, which includes humans and great apes, is recognized for unique complex social behavior and intellectual abilities. Despite the increasing genome data, however, the genomic origin of its phenotypic uniqueness has remained elusive. Clade-specific genes and highly conserved noncoding sequences (HCNSs) are among the high-potential evolutionary candidates involved in driving clade-specific characters and phenotypes. On this premise, we analyzed whole genome sequences along with gene orthology data retrieved from major DNA databases to find Hominidae-specific (HS) genes and HCNSs. We discovered that Down syndrome critical region 4 (DSCR4) is the only experimentally verified gene uniquely present in Hominidae. DSCR4 has no structural homology to any known protein and was inferred to have emerged in several steps through LTR/ERV1, LTR/ERVL retrotransposition, and transversion. Using the genomic distance as neutral evolution threshold, we identified 1,658 HS HCNSs. Polymorphism coverage and derived allele frequency analysis of HS HCNSs showed that these HCNSs are under purifying selection, indicating that they may harbor important functions. They are overrepresented in promoters/untranslated regions, in close proximity of genes involved in sensory perception of sound and developmental process, and also showed a significantly lower nucleosome occupancy probability. Interestingly, many ancestral sequences of the HS HCNSs showed very high evolutionary rates. This suggests that new functions emerged through some kind of positive selection, and then purifying selection started to operate to keep these functions. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  19. Modeling coding-sequence evolution within the context of residue solvent accessibility.

    PubMed

    Scherrer, Michael P; Meyer, Austin G; Wilke, Claus O

    2012-09-12

    Protein structure mediates site-specific patterns of sequence divergence. In particular, residues in the core of a protein (solvent-inaccessible residues) tend to be more evolutionarily conserved than residues on the surface (solvent-accessible residues). Here, we present a model of sequence evolution that explicitly accounts for the relative solvent accessibility of each residue in a protein. Our model is a variant of the Goldman-Yang 1994 (GY94) model in which all model parameters can be functions of the relative solvent accessibility (RSA) of a residue. We apply this model to a data set comprised of nearly 600 yeast genes, and find that an evolutionary-rate ratio ω that varies linearly with RSA provides a better model fit than an RSA-independent ω or an ω that is estimated separately in individual RSA bins. We further show that the branch length t and the transition-transverion ratio κ also vary with RSA. The RSA-dependent GY94 model performs better than an RSA-dependent Muse-Gaut 1994 (MG94) model in which the synonymous and non-synonymous rates individually are linear functions of RSA. Finally, protein core size affects the slope of the linear relationship between ω and RSA, and gene expression level affects both the intercept and the slope. Structure-aware models of sequence evolution provide a significantly better fit than traditional models that neglect structure. The linear relationship between ω and RSA implies that genes are better characterized by their ω slope and intercept than by just their mean ω.

  20. Targeted Sequencing of Venom Genes from Cone Snail Genomes Improves Understanding of Conotoxin Molecular Evolution

    PubMed Central

    Mahardika, Gusti N

    2018-01-01

    Abstract To expand our capacity to discover venom sequences from the genomes of venomous organisms, we applied targeted sequencing techniques to selectively recover venom gene superfamilies and nontoxin loci from the genomes of 32 cone snail species (family, Conidae), a diverse group of marine gastropods that capture their prey using a cocktail of neurotoxic peptides (conotoxins). We were able to successfully recover conotoxin gene superfamilies across all species with high confidence (> 100× coverage) and used these data to provide new insights into conotoxin evolution. First, we found that conotoxin gene superfamilies are composed of one to six exons and are typically short in length (mean = ∼85 bp). Second, we expanded our understanding of the following genetic features of conotoxin evolution: 1) positive selection, where exons coding the mature toxin region were often three times more divergent than their adjacent noncoding regions, 2) expression regulation, with comparisons to transcriptome data showing that cone snails only express a fraction of the genes available in their genome (24–63%), and 3) extensive gene turnover, where Conidae species varied from 120 to 859 conotoxin gene copies. Finally, using comparative phylogenetic methods, we found that while diet specificity did not predict patterns of conotoxin evolution, dietary breadth was positively correlated with total conotoxin gene diversity. Overall, the targeted sequencing technique demonstrated here has the potential to radically increase the pace at which venom gene families are sequenced and studied, reshaping our ability to understand the impact of genetic changes on ecologically relevant phenotypes and subsequent diversification. PMID:29514313

  1. Contribution of Primordial Binary Evolution to the Two Blue-straggler Sequences in Globular Cluster M30

    NASA Astrophysics Data System (ADS)

    Jiang, Dengkai; Chen, Xuefei; Li, Lifang; Han, Zhanwen

    2017-11-01

    Two blue-straggler sequences discovered in globular cluster M30 provide a strong constraint on the formation mechanisms of blue stragglers. We study the formation of blue-straggler binaries through binary evolution, and find that binary evolution can contribute to the blue stragglers in both of the sequences. Whether a blue-straggler is located in the blue sequence or red sequence depends on the contribution of the mass donor to the total luminosity of the binary, which is generally observed as a single star in globular clusters. The blue stragglers in the blue sequence have a cool white dwarf companion, while the majority (˜60%) of the objects in the red sequence are binaries that are still experiencing mass transfer. However, there are also some objects for which the donors have just finished the mass transfer (the stripped-core stars, ˜10%) or the blue stragglers (the accretors) have evolved away from the blue sequence (˜30%). Meanwhile, W UMa contact binaries found in both sequences may be explained by various mass ratios, that is, W UMa contact binaries in the red sequence have two components with comparable masses (e.g., mass ratio q ˜ 0.3-1.0), while those in the blue sequence have low mass ratios (e.g., q< 0.3). However, the fraction of the blue sequence in M30 cannot be reproduced by binary population synthesis if we assumed the initial parameters of a binary sample to be the same as those of the field. This possibly indicates that dynamical effects on binary systems are very important in globular clusters.

  2. Evolution of Sphingomonad Gene Clusters Related to Pesticide Catabolism Revealed by Genome Sequence and Mobilomics of Sphingobium herbicidovorans MH.

    PubMed

    Nielsen, Tue Kjærgaard; Rasmussen, Morten; Demanèche, Sandrine; Cecillon, Sébastien; Vogel, Timothy M; Hansen, Lars Hestbjerg

    2017-09-01

    Bacterial degraders of chlorophenoxy herbicides have been isolated from various ecosystems, including pristine environments. Among these degraders, the sphingomonads constitute a prominent group that displays versatile xenobiotic-degradation capabilities. Four separate sequencing strategies were required to provide the complete sequence of the complex and plastic genome of the canonical chlorophenoxy herbicide-degrading Sphingobium herbicidovorans MH. The genome has an intricate organization of the chlorophenoxy-herbicide catabolic genes sdpA, rdpA, and cadABCD that encode the (R)- and (S)-enantiomer-specific 2,4-dichlorophenoxypropionate dioxygenases and four subunits of a Rieske non-heme iron oxygenase involved in 2-methyl-chlorophenoxyacetic acid degradation, respectively. Several major genomic rearrangements are proposed to help understand the evolution and mobility of these important genes and their genetic context. Single-strain mobilomic sequence analysis uncovered plasmids and insertion sequence-associated circular intermediates in this environmentally important bacterium and enabled the description of evolutionary models for pesticide degradation in strain MH and related organisms. The mobilome presented a complex mosaic of mobile genetic elements including four plasmids and several circular intermediate DNA molecules of insertion-sequence elements and transposons that are central to the evolution of xenobiotics degradation. Furthermore, two individual chromosomally integrated prophages were shown to excise and form free circular DNA molecules. This approach holds great potential for improving the understanding of genome plasticity, evolution, and microbial ecology. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  3. Evidence of accelerated evolution and ectodermal-specific expression of presumptive BDS toxin cDNAs from Anemonia viridis.

    PubMed

    Nicosia, Aldo; Maggio, Teresa; Mazzola, Salvatore; Cuttitta, Angela

    2013-10-30

    Anemonia viridis is a widespread and extensively studied Mediterranean species of sea anemone from which a large number of polypeptide toxins, such as blood depressing substances (BDS) peptides, have been isolated. The first members of this class, BDS-1 and BDS-2, are polypeptides belonging to the β-defensin fold family and were initially described for their antihypertensive and antiviral activities. BDS-1 and BDS-2 are 43 amino acid peptides characterised by three disulfide bonds that act as neurotoxins affecting Kv3.1, Kv3.2 and Kv3.4 channel gating kinetics. In addition, BDS-1 inactivates the Nav1.7 and Nav1.3 channels. The development of a large dataset of A. viridis expressed sequence tags (ESTs) and the identification of 13 putative BDS-like cDNA sequences has attracted interest, especially as scientific and diagnostic tools. A comparison of BDS cDNA sequences showed that the untranslated regions are more conserved than the protein-coding regions. Moreover, the KA/KS ratios calculated for all pairwise comparisons showed values greater than 1, suggesting mechanisms of accelerated evolution. The structures of the BDS homologs were predicted by molecular modelling. All toxins possess similar 3D structures that consist of a triple-stranded antiparallel β-sheet and an additional small antiparallel β-sheet located downstream of the cleavage/maturation site; however, the orientation of the triple-stranded β-sheet appears to differ among the toxins. To characterise the spatial expression profile of the putative BDS cDNA sequences, tissue-specific cDNA libraries, enriched for BDS transcripts, were constructed. In addition, the proper amplification of ectodermal or endodermal markers ensured the tissue specificity of each library. Sequencing randomly selected clones from each library revealed ectodermal-specific expression of ten BDS transcripts, while transcripts of BDS-8, BDS-13, BDS-14 and BDS-15 failed to be retrieved, likely due to under-representation in our

  4. Focal plane AIT sequence: evolution from HRG-Spot 5 to Pleiades HR

    NASA Astrophysics Data System (ADS)

    Le Goff, Roland; Pranyies, Pascal; Toubhans, Isabelle

    2017-11-01

    Optical and geometrical image qualities of Focal Planes, for "push-broom" high resolution remote sensing satellites, require the implementation of specific means and methods for the AIT sequence. Indeed the geometric performances of the focal plane mainly axial focusing and transverse registration, are duly obtained on the basis of adjustment, setting and measurement of optical and CCD components with an accuracy of a few microns. Since the end of the 1970s, EADS-SODERN has developed a series of detection units for earth observation instruments like SPOT and Helios. And EADS-SODERN is now responsible for the development of the Pleiades High Resolution Focal Plane assembly. This paper presents the AIT sequences. We introduce all the efforts, innovative solutions and improvements made on the assembly facilities to match the technical evolutions and breakthrough of the Pleiades HR FP concept in comparison with the previous High Resolution Geometric SPOT 5 Focal Plane. The main evolution drivers are the implementation of strip filters and the realization of 400 mm continuous retinas. For Pleiades HR AIT sequence, three specific integration and measuring benches, corresponding with the different assembly stages, are used: a 3-D non-contact measurement machine for the assembly of detection module, a 3-D measurement machine for mirror integration on the main Focal Plane SiC structure, and a 3-D geometric coordinates control bench to focus detection module lines and to ensure they are well registered together.

  5. Sexual selection accelerates signal evolution during speciation in birds.

    PubMed

    Seddon, Nathalie; Botero, Carlos A; Tobias, Joseph A; Dunn, Peter O; Macgregor, Hannah E A; Rubenstein, Dustin R; Uy, J Albert C; Weir, Jason T; Whittingham, Linda A; Safran, Rebecca J

    2013-09-07

    Sexual selection is proposed to be an important driver of diversification in animal systems, yet previous tests of this hypothesis have produced mixed results and the mechanisms involved remain unclear. Here, we use a novel phylogenetic approach to assess the influence of sexual selection on patterns of evolutionary change during 84 recent speciation events across 23 passerine bird families. We show that elevated levels of sexual selection are associated with more rapid phenotypic divergence between related lineages, and that this effect is restricted to male plumage traits proposed to function in mate choice and species recognition. Conversely, we found no evidence that sexual selection promoted divergence in female plumage traits, or in male traits related to foraging and locomotion. These results provide strong evidence that female choice and male-male competition are dominant mechanisms driving divergence during speciation in birds, potentially linking sexual selection to the accelerated evolution of pre-mating reproductive isolation.

  6. Snake mitochondrial genomes: phylogenetic relationships and implications of extended taxon sampling for interpretations of mitogenomic evolution

    PubMed Central

    2010-01-01

    Background Snake mitochondrial genomes are of great interest in understanding mitogenomic evolution because of gene duplications and rearrangements and the fast evolutionary rate of their genes compared to other vertebrates. Mitochondrial gene sequences have also played an important role in attempts to resolve the contentious phylogenetic relationships of especially the early divergences among alethinophidian snakes. Two recent innovative studies found dramatic gene- and branch-specific relative acceleration in snake protein-coding gene evolution, particularly along internal branches leading to Serpentes and Alethinophidia. It has been hypothesized that some of these rate shifts are temporally (and possibly causally) associated with control region duplication and/or major changes in ecology and anatomy. Results The near-complete mitochondrial (mt) genomes of three henophidian snakes were sequenced: Anilius scytale, Rhinophis philippinus, and Charina trivirgata. All three genomes share a duplicated control region and translocated tRNALEU, derived features found in all alethinophidian snakes studied to date. The new sequence data were aligned with mt genome data for 21 other species of snakes and used in phylogenetic analyses. Phylogenetic results agreed with many other studies in recovering several robust clades, including Colubroidea, Caenophidia, and Cylindrophiidae+Uropeltidae. Nodes within Henophidia that have been difficult to resolve robustly in previous analyses remained uncompellingly resolved here. Comparisons of relative rates of evolution of rRNA vs. protein-coding genes were conducted by estimating branch lengths across the tree. Our expanded sampling revealed dramatic acceleration along the branch leading to Typhlopidae, particularly long rRNA terminal branches within Scolecophidia, and that most of the dramatic acceleration in protein-coding gene rate along Serpentes and Alethinophidia branches occurred before Anilius diverged from other

  7. PROFESS: a PROtein Function, Evolution, Structure and Sequence database

    PubMed Central

    Triplet, Thomas; Shortridge, Matthew D.; Griep, Mark A.; Stark, Jaime L.; Powers, Robert; Revesz, Peter

    2010-01-01

    The proliferation of biological databases and the easy access enabled by the Internet is having a beneficial impact on biological sciences and transforming the way research is conducted. There are ∼1100 molecular biology databases dispersed throughout the Internet. To assist in the functional, structural and evolutionary analysis of the abundant number of novel proteins continually identified from whole-genome sequencing, we introduce the PROFESS (PROtein Function, Evolution, Structure and Sequence) database. Our database is designed to be versatile and expandable and will not confine analysis to a pre-existing set of data relationships. A fundamental component of this approach is the development of an intuitive query system that incorporates a variety of similarity functions capable of generating data relationships not conceived during the creation of the database. The utility of PROFESS is demonstrated by the analysis of the structural drift of homologous proteins and the identification of potential pancreatic cancer therapeutic targets based on the observation of protein–protein interaction networks. Database URL: http://cse.unl.edu/∼profess/ PMID:20624718

  8. The Genome Sequence of Taurine Cattle: A Window to Ruminant Biology and Evolution

    USDA-ARS?s Scientific Manuscript database

    As a major step toward understanding the biology and evolution of ruminants, the cattle genome was sequenced to ~7x coverage using a combined whole genome shotgun and BAC skim approach. The cattle genome contains a minimum of 22,000 genes, with a core set of 14,345 orthologs found in seven mammalian...

  9. Ginkgo and Welwitschia Mitogenomes Reveal Extreme Contrasts in Gymnosperm Mitochondrial Evolution.

    PubMed

    Guo, Wenhu; Grewe, Felix; Fan, Weishu; Young, Gregory J; Knoop, Volker; Palmer, Jeffrey D; Mower, Jeffrey P

    2016-06-01

    Mitochondrial genomes (mitogenomes) of flowering plants are well known for their extreme diversity in size, structure, gene content, and rates of sequence evolution and recombination. In contrast, little is known about mitogenomic diversity and evolution within gymnosperms. Only a single complete genome sequence is available, from the cycad Cycas taitungensis, while limited information is available for the one draft sequence, from Norway spruce (Picea abies). To examine mitogenomic evolution in gymnosperms, we generated complete genome sequences for the ginkgo tree (Ginkgo biloba) and a gnetophyte (Welwitschia mirabilis). There is great disparity in size, sequence conservation, levels of shared DNA, and functional content among gymnosperm mitogenomes. The Cycas and Ginkgo mitogenomes are relatively small, have low substitution rates, and possess numerous genes, introns, and edit sites; we infer that these properties were present in the ancestral seed plant. By contrast, the Welwitschia mitogenome has an expanded size coupled with accelerated substitution rates and extensive loss of these functional features. The Picea genome has expanded further, to more than 4 Mb. With regard to structural evolution, the Cycas and Ginkgo mitogenomes share a remarkable amount of intergenic DNA, which may be related to the limited recombinational activity detected at repeats in Ginkgo Conversely, the Welwitschia mitogenome shares almost no intergenic DNA with any other seed plant. By conducting the first measurements of rates of DNA turnover in seed plant mitogenomes, we discovered that turnover rates vary by orders of magnitude among species. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  10. ProteomeVis: a web app for exploration of protein properties from structure to sequence evolution across organisms' proteomes.

    PubMed

    Razban, Rostam M; Gilson, Amy I; Durfee, Niamh; Strobelt, Hendrik; Dinkla, Kasper; Choi, Jeong-Mo; Pfister, Hanspeter; Shakhnovich, Eugene I

    2018-05-08

    Protein evolution spans time scales and its effects span the length of an organism. A web app named ProteomeVis is developed to provide a comprehensive view of protein evolution in the S. cerevisiae and E. coli proteomes. ProteomeVis interactively creates protein chain graphs, where edges between nodes represent structure and sequence similarities within user-defined ranges, to study the long time scale effects of protein structure evolution. The short time scale effects of protein sequence evolution are studied by sequence evolutionary rate (ER) correlation analyses with protein properties that span from the molecular to the organismal level. We demonstrate the utility and versatility of ProteomeVis by investigating the distribution of edges per node in organismal protein chain universe graphs (oPCUGs) and putative ER determinants. S. cerevisiae and E. coli oPCUGs are scale-free with scaling constants of 1.79 and 1.56, respectively. Both scaling constants can be explained by a previously reported theoretical model describing protein structure evolution (Dokholyan et al., 2002). Protein abundance most strongly correlates with ER among properties in ProteomeVis, with Spearman correlations of -0.49 (p-value<10-10) and -0.46 (p-value<10-10) for S. cerevisiae and E. coli, respectively. This result is consistent with previous reports that found protein expression to be the most important ER determinant (Zhang and Yang, 2015). ProteomeVis is freely accessible at http://proteomevis.chem.harvard.edu. Supplementary data are available at Bioinformatics. shakhnovich@chemistry.harvard.edu.

  11. Comparative Analyses of DNA Methylation and Sequence Evolution Using Nasonia Genomes

    PubMed Central

    Park, Jungsun; Peng, Zuogang; Zeng, Jia; Elango, Navin; Park, Taesung; Wheeler, Dave; Werren, John H.; Yi, Soojin V.

    2011-01-01

    The functional and evolutionary significance of DNA methylation in insect genomes remains to be resolved. Nasonia is well situated for comparative analyses of DNA methylation and genome evolution, since the genomes of a moderately distant outgroup species as well as closely related sibling species are available. Using direct sequencing of bisulfite-converted DNA, we uncovered a substantial level of DNA methylation in 17 of 18 Nasonia vitripennis genes and a strong correlation between methylation level and CpG depletion. Notably, in the sex-determining locus transformer, the exon that is alternatively spliced between the sexes is heavily methylated in both males and females, whereas other exons are only sparsely methylated. Orthologous genes of the honeybee and Nasonia show highly similar relative levels of CpG depletion, despite ∼190 My divergence. Densely and sparsely methylated genes in these species also exhibit similar functional enrichments. We found that the degree of CpG depletion is negatively correlated with substitution rates between closely related Nasonia species for synonymous, nonsynonymous, and intron sites. This suggests that mutation rates increase with decreasing levels of germ line methylation. Thus, DNA methylation is prevalent in the Nasonia genome, may participate in regulatory processes such as sex determination and alternative splicing, and is correlated with several aspects of genome and sequence evolution. PMID:21693438

  12. Comparable contributions of structural-functional constraints and expression level to the rate of protein sequence evolution

    PubMed Central

    Wolf, Maxim Y; Wolf, Yuri I; Koonin, Eugene V

    2008-01-01

    Background Proteins show a broad range of evolutionary rates. Understanding the factors that are responsible for the characteristic rate of evolution of a given protein arguably is one of the major goals of evolutionary biology. A long-standing general assumption used to be that the evolution rate is, primarily, determined by the specific functional constraints that affect the given protein. These constrains were traditionally thought to depend both on the specific features of the protein's structure and its biological role. The advent of systems biology brought about new types of data, such as expression level and protein-protein interactions, and unexpectedly, a variety of correlations between protein evolution rate and these variables have been observed. The strongest connections by far were repeatedly seen between protein sequence evolution rate and the expression level of the respective gene. It has been hypothesized that this link is due to the selection for the robustness of the protein structure to mistranslation-induced misfolding that is particularly important for highly expressed proteins and is the dominant determinant of the sequence evolution rate. Results This work is an attempt to assess the relative contributions of protein domain structure and function, on the one hand, and expression level on the other hand, to the rate of sequence evolution. To this end, we performed a genome-wide analysis of the effect of the fusion of a pair of domains in multidomain proteins on the difference in the domain-specific evolutionary rates. The mistranslation-induced misfolding hypothesis would predict that, within multidomain proteins, fused domains, on average, should evolve at substantially closer rates than the same domains in different proteins because, within a mutlidomain protein, all domains are translated at the same rate. We performed a comprehensive comparison of the evolutionary rates of mammalian and plant protein domains that are either joined in

  13. Systematic Analysis of Long Noncoding RNAs in the Senescence-accelerated Mouse Prone 8 Brain Using RNA Sequencing.

    PubMed

    Zhang, Shuai; Qin, Chunxia; Cao, Guoqiong; Xin, Wenfeng; Feng, Chengqiang; Zhang, Wensheng

    2016-08-02

    Long noncoding RNAs (lncRNAs) may play an important role in Alzheimer's disease (AD) pathogenesis. However, despite considerable research in this area, the comprehensive and systematic understanding of lncRNAs in AD is still limited. The emergence of RNA sequencing provides a predictor and has incomparable advantage compared with other methods, including microarray. In this study, we identified lncRNAs in a 7-month-old mouse brain through deep RNA sequencing using the senescence-accelerated mouse prone 8 (SAMP8) and senescence-accelerated mouse resistant 1 (SAMR1) models. A total of 599,985,802 clean reads and 23,334 lncRNA transcripts were obtained. Then, we identified 97 significantly upregulated and 114 significantly downregulated lncRNA transcripts from all cases in SAMP8 mice relative to SAMR1 mice. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these significantly dysregulated lncRNAs were involved in regulating the development of AD from various angles, such as nerve growth factor term (GO: 1990089), mitogen-activated protein kinase signaling pathway, and AD pathway. Furthermore, the most probable AD-associated lncRNAs were predicted and listed in detail. Our study provided the systematic dissection of lncRNA profiling in SAMP8 mouse brain and accelerated the development of lncRNA biomarkers in AD. These attracting biomarkers could provide significant insights into AD therapy in the future.

  14. Adaptive Mistranslation Accelerates the Evolution of Fluconazole Resistance and Induces Major Genomic and Gene Expression Alterations in Candida albicans

    PubMed Central

    Santamaría, Rodrigo; Lee, Wanseon; Rung, Johan; Tocci, Noemi; Abbey, Darren; Bezerra, Ana R.; Carreto, Laura; Moura, Gabriela R.; Bayés, Mónica; Gut, Ivo G.; Csikasz-Nagy, Attila; Cavalieri, Duccio; Berman, Judith

    2017-01-01

    ABSTRACT Regulated erroneous protein translation (adaptive mistranslation) increases proteome diversity and produces advantageous phenotypic variability in the human pathogen Candida albicans. It also increases fitness in the presence of fluconazole, but the underlying molecular mechanism is not understood. To address this question, we evolved hypermistranslating and wild-type strains in the absence and presence of fluconazole and compared their fluconazole tolerance and resistance trajectories during evolution. The data show that mistranslation increases tolerance and accelerates the acquisition of resistance to fluconazole. Genome sequencing, array-based comparative genome analysis, and gene expression profiling revealed that during the course of evolution in fluconazole, the range of mutational and gene deregulation differences was distinctively different and broader in the hypermistranslating strain, including multiple chromosome duplications, partial chromosome deletions, and polyploidy. Especially, the increased accumulation of loss-of-heterozygosity events, aneuploidy, translational and cell surface modifications, and differences in drug efflux seem to mediate more rapid drug resistance acquisition under mistranslation. Our observations support a pivotal role for adaptive mistranslation in the evolution of drug resistance in C. albicans. IMPORTANCE Infectious diseases caused by drug-resistant fungi are an increasing threat to public health because of the high mortality rates and high costs associated with treatment. Thus, understanding of the molecular mechanisms of drug resistance is of crucial interest for the medical community. Here we investigated the role of regulated protein mistranslation, a characteristic mechanism used by C. albicans to diversify its proteome, in the evolution of fluconazole resistance. Such codon ambiguity is usually considered highly deleterious, yet recent studies found that mistranslation can boost adaptation in stressful

  15. A coarse-grained biophysical model of sequence evolution and the population size dependence of the speciation rate

    PubMed Central

    Khatri, Bhavin S.; Goldstein, Richard A.

    2015-01-01

    Speciation is fundamental to understanding the huge diversity of life on Earth. Although still controversial, empirical evidence suggests that the rate of speciation is larger for smaller populations. Here, we explore a biophysical model of speciation by developing a simple coarse-grained theory of transcription factor-DNA binding and how their co-evolution in two geographically isolated lineages leads to incompatibilities. To develop a tractable analytical theory, we derive a Smoluchowski equation for the dynamics of binding energy evolution that accounts for the fact that natural selection acts on phenotypes, but variation arises from mutations in sequences; the Smoluchowski equation includes selection due to both gradients in fitness and gradients in sequence entropy, which is the logarithm of the number of sequences that correspond to a particular binding energy. This simple consideration predicts that smaller populations develop incompatibilities more quickly in the weak mutation regime; this trend arises as sequence entropy poises smaller populations closer to incompatible regions of phenotype space. These results suggest a generic coarse-grained approach to evolutionary stochastic dynamics, allowing realistic modelling at the phenotypic level. PMID:25936759

  16. Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution.

    PubMed

    2004-12-09

    We present here a draft genome sequence of the red jungle fowl, Gallus gallus. Because the chicken is a modern descendant of the dinosaurs and the first non-mammalian amniote to have its genome sequenced, the draft sequence of its genome--composed of approximately one billion base pairs of sequence and an estimated 20,000-23,000 genes--provides a new perspective on vertebrate genome evolution, while also improving the annotation of mammalian genomes. For example, the evolutionary distance between chicken and human provides high specificity in detecting functional elements, both non-coding and coding. Notably, many conserved non-coding sequences are far from genes and cannot be assigned to defined functional classes. In coding regions the evolutionary dynamics of protein domains and orthologous groups illustrate processes that distinguish the lineages leading to birds and mammals. The distinctive properties of avian microchromosomes, together with the inferred patterns of conserved synteny, provide additional insights into vertebrate chromosome architecture.

  17. Organization and evolution of highly repeated satellite DNA sequences in plant chromosomes.

    PubMed

    Sharma, S; Raina, S N

    2005-01-01

    A major component of the plant nuclear genome is constituted by different classes of repetitive DNA sequences. The structural, functional and evolutionary aspects of the satellite repetitive DNA families, and their organization in the chromosomes is reviewed. The tandem satellite DNA sequences exhibit characteristic chromosomal locations, usually at subtelomeric and centromeric regions. The repetitive DNA family(ies) may be widely distributed in a taxonomic family or a genus, or may be specific for a species, genome or even a chromosome. They may acquire large-scale variations in their sequence and copy number over an evolutionary time-scale. These features have formed the basis of extensive utilization of repetitive sequences for taxonomic and phylogenetic studies. Hybrid polyploids have especially proven to be excellent models for studying the evolution of repetitive DNA sequences. Recent studies explicitly show that some repetitive DNA families localized at the telomeres and centromeres have acquired important structural and functional significance. The repetitive elements are under different evolutionary constraints as compared to the genes. Satellite DNA families are thought to arise de novo as a consequence of molecular mechanisms such as unequal crossing over, rolling circle amplification, replication slippage and mutation that constitute "molecular drive". Copyright 2005 S. Karger AG, Basel.

  18. Single-cell sequencing and tumorigenesis: improved understanding of tumor evolution and metastasis.

    PubMed

    Ellsworth, Darrell L; Blackburn, Heather L; Shriver, Craig D; Rabizadeh, Shahrooz; Soon-Shiong, Patrick; Ellsworth, Rachel E

    2017-12-01

    Extensive genomic and transcriptomic heterogeneity in human cancer often negatively impacts treatment efficacy and survival, thus posing a significant ongoing challenge for modern treatment regimens. State-of-the-art DNA- and RNA-sequencing methods now provide high-resolution genomic and gene expression portraits of individual cells, facilitating the study of complex molecular heterogeneity in cancer. Important developments in single-cell sequencing (SCS) technologies over the past 5 years provide numerous advantages over traditional sequencing methods for understanding the complexity of carcinogenesis, but significant hurdles must be overcome before SCS can be clinically useful. In this review, we: (1) highlight current methodologies and recent technological advances for isolating single cells, single-cell whole-genome and whole-transcriptome amplification using minute amounts of nucleic acids, and SCS, (2) summarize research investigating molecular heterogeneity at the genomic and transcriptomic levels and how this heterogeneity affects clonal evolution and metastasis, and (3) discuss the promise for integrating SCS in the clinical care arena for improved patient care.

  19. Evolution of Sphingomonad Gene Clusters Related to Pesticide Catabolism Revealed by Genome Sequence and Mobilomics of Sphingobium herbicidovorans MH

    PubMed Central

    Nielsen, Tue Kjærgaard; Rasmussen, Morten; Demanèche, Sandrine; Cecillon, Sébastien; Vogel, Timothy M.

    2017-01-01

    Abstract Bacterial degraders of chlorophenoxy herbicides have been isolated from various ecosystems, including pristine environments. Among these degraders, the sphingomonads constitute a prominent group that displays versatile xenobiotic-degradation capabilities. Four separate sequencing strategies were required to provide the complete sequence of the complex and plastic genome of the canonical chlorophenoxy herbicide-degrading Sphingobium herbicidovorans MH. The genome has an intricate organization of the chlorophenoxy-herbicide catabolic genes sdpA, rdpA, and cadABCD that encode the (R)- and (S)-enantiomer-specific 2,4-dichlorophenoxypropionate dioxygenases and four subunits of a Rieske non-heme iron oxygenase involved in 2-methyl-chlorophenoxyacetic acid degradation, respectively. Several major genomic rearrangements are proposed to help understand the evolution and mobility of these important genes and their genetic context. Single-strain mobilomic sequence analysis uncovered plasmids and insertion sequence-associated circular intermediates in this environmentally important bacterium and enabled the description of evolutionary models for pesticide degradation in strain MH and related organisms. The mobilome presented a complex mosaic of mobile genetic elements including four plasmids and several circular intermediate DNA molecules of insertion-sequence elements and transposons that are central to the evolution of xenobiotics degradation. Furthermore, two individual chromosomally integrated prophages were shown to excise and form free circular DNA molecules. This approach holds great potential for improving the understanding of genome plasticity, evolution, and microbial ecology. PMID:28961970

  20. Plastid-Nuclear Interaction and Accelerated Coevolution in Plastid Ribosomal Genes in Geraniaceae.

    PubMed

    Weng, Mao-Lun; Ruhlman, Tracey A; Jansen, Robert K

    2016-06-27

    Plastids and mitochondria have many protein complexes that include subunits encoded by organelle and nuclear genomes. In animal cells, compensatory evolution between mitochondrial and nuclear-encoded subunits was identified and the high mitochondrial mutation rates were hypothesized to drive compensatory evolution in nuclear genomes. In plant cells, compensatory evolution between plastid and nucleus has rarely been investigated in a phylogenetic framework. To investigate plastid-nuclear coevolution, we focused on plastid ribosomal protein genes that are encoded by plastid and nuclear genomes from 27 Geraniales species. Substitution rates were compared for five sets of genes representing plastid- and nuclear-encoded ribosomal subunit proteins targeted to the cytosol or the plastid as well as nonribosomal protein controls. We found that nonsynonymous substitution rates (dN) and the ratios of nonsynonymous to synonymous substitution rates (ω) were accelerated in both plastid- (CpRP) and nuclear-encoded subunits (NuCpRP) of the plastid ribosome relative to control sequences. Our analyses revealed strong signals of cytonuclear coevolution between plastid- and nuclear-encoded subunits, in which nonsynonymous substitutions in CpRP and NuCpRP tend to occur along the same branches in the Geraniaceae phylogeny. This coevolution pattern cannot be explained by physical interaction between amino acid residues. The forces driving accelerated coevolution varied with cellular compartment of the sequence. Increased ω in CpRP was mainly due to intensified positive selection whereas increased ω in NuCpRP was caused by relaxed purifying selection. In addition, the many indels identified in plastid rRNA genes in Geraniaceae may have contributed to changes in plastid subunits. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Genetic evolution of pancreatic cancer: lessons learnt from the pancreatic cancer genome sequencing project

    PubMed Central

    Iacobuzio-Donahue, Christine A

    2012-01-01

    Pancreatic cancer is a disease caused by the accumulation of genetic alterations in specific genes. Elucidation of the human genome sequence, in conjunction with technical advances in the ability to perform whole exome sequencing, have provided new insight into the mutational spectra characteristic of this lethal tumour type. Most recently, exomic sequencing has been used to clarify the clonal evolution of pancreatic cancer as well as provide time estimates of pancreatic carcinogenesis, indicating that a long window of opportunity may exist for early detection of this disease while in the curative stage. Moving forward, these mutational analyses indicate potential targets for personalised diagnostic and therapeutic intervention as well as the optimal timing for intervention based on the natural history of pancreatic carcinogenesis and progression. PMID:21749982

  2. Molecular phylogeny, population genetics, and evolution of heterocystous cyanobacteria using nifH gene sequences.

    PubMed

    Singh, Prashant; Singh, Satya Shila; Elster, Josef; Mishra, Arun Kumar

    2013-06-01

    In order to assess phylogeny, population genetics, and approximation of future course of cyanobacterial evolution based on nifH gene sequences, 41 heterocystous cyanobacterial strains collected from all over India have been used in the present study. NifH gene sequence analysis data confirm that the heterocystous cyanobacteria are monophyletic while the stigonematales show polyphyletic origin with grave intermixing. Further, analysis of nifH gene sequence data using intricate mathematical extrapolations revealed that the nucleotide diversity and recombination frequency is much greater in Nostocales than the Stigonematales. Similarly, DNA divergence studies showed significant values of divergence with greater gene conversion tracts in the unbranched (Nostocales) than the branched (Stigonematales) strains. Our data strongly support the origin of true branching cyanobacterial strains from the unbranched strains.

  3. Generic accelerated sequence alignment in SeqAn using vectorization and multi-threading.

    PubMed

    Rahn, René; Budach, Stefan; Costanza, Pascal; Ehrhardt, Marcel; Hancox, Jonny; Reinert, Knut

    2018-05-03

    Pairwise sequence alignment is undoubtedly a central tool in many bioinformatics analyses. In this paper, we present a generically accelerated module for pairwise sequence alignments applicable for a broad range of applications. In our module, we unified the standard dynamic programming kernel used for pairwise sequence alignments and extended it with a generalized inter-sequence vectorization layout, such that many alignments can be computed simultaneously by exploiting SIMD (Single Instruction Multiple Data) instructions of modern processors. We then extended the module by adding two layers of thread-level parallelization, where we a) distribute many independent alignments on multiple threads and b) inherently parallelize a single alignment computation using a work stealing approach producing a dynamic wavefront progressing along the minor diagonal. We evaluated our alignment vectorization and parallelization on different processors, including the newest Intel® Xeon® (Skylake) and Intel® Xeon Phi™ (KNL) processors, and use cases. The instruction set AVX512-BW (Byte and Word), available on Skylake processors, can genuinely improve the performance of vectorized alignments. We could run single alignments 1600 times faster on the Xeon Phi™ and 1400 times faster on the Xeon® than executing them with our previous sequential alignment module. The module is programmed in C++ using the SeqAn (Reinert et al., 2017) library and distributed with version 2.4. under the BSD license. We support SSE4, AVX2, AVX512 instructions and included UME::SIMD, a SIMD-instruction wrapper library, to extend our module for further instruction sets. We thoroughly test all alignment components with all major C++ compilers on various platforms. rene.rahn@fu-berlin.de.

  4. Evolution of transcriptional enhancers and animal diversity

    PubMed Central

    Rubinstein, Marcelo; de Souza, Flávio S. J.

    2013-01-01

    Deciphering the genetic bases that drive animal diversity is one of the major challenges of modern biology. Although four decades ago it was proposed that animal evolution was mainly driven by changes in cis-regulatory DNA elements controlling gene expression rather than in protein-coding sequences, only now are powerful bioinformatics and experimental approaches available to accelerate studies into how the evolution of transcriptional enhancers contributes to novel forms and functions. In the introduction to this Theme Issue, we start by defining the general properties of transcriptional enhancers, such as modularity and the coexistence of tight sequence conservation with transcription factor-binding site shuffling as different mechanisms that maintain the enhancer grammar over evolutionary time. We discuss past and current methods used to identify cell-type-specific enhancers and provide examples of how enhancers originate de novo, change and are lost in particular lineages. We then focus in the central part of this Theme Issue on analysing examples of how the molecular evolution of enhancers may change form and function. Throughout this introduction, we present the main findings of the articles, reviews and perspectives contributed to this Theme Issue that together illustrate some of the great advances and current frontiers in the field. PMID:24218630

  5. Origin of noncoding DNA sequences: molecular fossils of genome evolution

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Naora, H.; Miyahara, K.; Curnow, R.N.

    The total amount of noncoding sequences on chromosomes of contemporary organisms varies significantly from species to species. The authors propose a hypothesis for the origin of these noncoding sequences that assumes that (i) an approx. 0.55-kilobase (kb)-long reading frame composed the primordial gene and (ii) a 20-kb-long single-stranded polynucleotide is the longest molecule (as a genome) that was polymerized at random and without a specific template in the primordial soup/cell. The statistical distribution of stop codons allows examination of the probability of generating reading frames of approx. 0.55 kb in this primordial polynucleotide. This analysis reveals that with three stopmore » codons, a run of at least 0.55-kb equivalent length of nonstop codons would occur in 4.6% of 20-kb-long polynucleotide molecules. They attempt to estimate the total amount of noncoding sequences that would be present on the chromosomes of contemporary species assuming that present-day chromosomes retain the prototype primordial genome structure. Theoretical estimates thus obtained for most eukaryotes do not differ significantly from those reported for these specific organisms, with only a few exceptions. Furthermore, analysis of possible stop-codon distributions suggests that life on earth would not exist, at least in its present form, had two or four stop codons been selected early in evolution.« less

  6. Evolution of EF-hand calcium-modulated proteins. III. Exon sequences confirm most dendrograms based on protein sequences: calmodulin dendrograms show significant lack of parallelism

    NASA Technical Reports Server (NTRS)

    Nakayama, S.; Kretsinger, R. H.

    1993-01-01

    In the first report in this series we presented dendrograms based on 152 individual proteins of the EF-hand family. In the second we used sequences from 228 proteins, containing 835 domains, and showed that eight of the 29 subfamilies are congruent and that the EF-hand domains of the remaining 21 subfamilies have diverse evolutionary histories. In this study we have computed dendrograms within and among the EF-hand subfamilies using the encoding DNA sequences. In most instances the dendrograms based on protein and on DNA sequences are very similar. Significant differences between protein and DNA trees for calmodulin remain unexplained. In our fourth report we evaluate the sequences and the distribution of introns within the EF-hand family and conclude that exon shuffling did not play a significant role in its evolution.

  7. Dynamic Monte Carlo simulations of radiatively accelerated GRB fireballs

    NASA Astrophysics Data System (ADS)

    Chhotray, Atul; Lazzati, Davide

    2018-05-01

    We present a novel Dynamic Monte Carlo code (DynaMo code) that self-consistently simulates the Compton-scattering-driven dynamic evolution of a plasma. We use the DynaMo code to investigate the time-dependent expansion and acceleration of dissipationless gamma-ray burst fireballs by varying their initial opacities and baryonic content. We study the opacity and energy density evolution of an initially optically thick, radiation-dominated fireball across its entire phase space - in particular during the Rph < Rsat regime. Our results reveal new phases of fireball evolution: a transition phase with a radial extent of several orders of magnitude - the fireball transitions from Γ ∝ R to Γ ∝ R0, a post-photospheric acceleration phase - where fireballs accelerate beyond the photosphere and a Thomson-dominated acceleration phase - characterized by slow acceleration of optically thick, matter-dominated fireballs due to Thomson scattering. We quantify the new phases by providing analytical expressions of Lorentz factor evolution, which will be useful for deriving jet parameters.

  8. Fast hydrological model calibration based on the heterogeneous parallel computing accelerated shuffled complex evolution method

    NASA Astrophysics Data System (ADS)

    Kan, Guangyuan; He, Xiaoyan; Ding, Liuqian; Li, Jiren; Hong, Yang; Zuo, Depeng; Ren, Minglei; Lei, Tianjie; Liang, Ke

    2018-01-01

    Hydrological model calibration has been a hot issue for decades. The shuffled complex evolution method developed at the University of Arizona (SCE-UA) has been proved to be an effective and robust optimization approach. However, its computational efficiency deteriorates significantly when the amount of hydrometeorological data increases. In recent years, the rise of heterogeneous parallel computing has brought hope for the acceleration of hydrological model calibration. This study proposed a parallel SCE-UA method and applied it to the calibration of a watershed rainfall-runoff model, the Xinanjiang model. The parallel method was implemented on heterogeneous computing systems using OpenMP and CUDA. Performance testing and sensitivity analysis were carried out to verify its correctness and efficiency. Comparison results indicated that heterogeneous parallel computing-accelerated SCE-UA converged much more quickly than the original serial version and possessed satisfactory accuracy and stability for the task of fast hydrological model calibration.

  9. Understanding the complex evolution of rapidly mutating viruses with deep sequencing: Beyond the analysis of viral diversity.

    PubMed

    Leung, Preston; Eltahla, Auda A; Lloyd, Andrew R; Bull, Rowena A; Luciani, Fabio

    2017-07-15

    With the advent of affordable deep sequencing technologies, detection of low frequency variants within genetically diverse viral populations can now be achieved with unprecedented depth and efficiency. The high-resolution data provided by next generation sequencing technologies is currently recognised as the gold standard in estimation of viral diversity. In the analysis of rapidly mutating viruses, longitudinal deep sequencing datasets from viral genomes during individual infection episodes, as well as at the epidemiological level during outbreaks, now allow for more sophisticated analyses such as statistical estimates of the impact of complex mutation patterns on the evolution of the viral populations both within and between hosts. These analyses are revealing more accurate descriptions of the evolutionary dynamics that underpin the rapid adaptation of these viruses to the host response, and to drug therapies. This review assesses recent developments in methods and provide informative research examples using deep sequencing data generated from rapidly mutating viruses infecting humans, particularly hepatitis C virus (HCV), human immunodeficiency virus (HIV), Ebola virus and influenza virus, to understand the evolution of viral genomes and to explore the relationship between viral mutations and the host adaptive immune response. Finally, we discuss limitations in current technologies, and future directions that take advantage of publically available large deep sequencing datasets. Copyright © 2016 Elsevier B.V. All rights reserved.

  10. Plastid–Nuclear Interaction and Accelerated Coevolution in Plastid Ribosomal Genes in Geraniaceae

    PubMed Central

    Weng, Mao-Lun; Ruhlman, Tracey A.; Jansen, Robert K.

    2016-01-01

    Plastids and mitochondria have many protein complexes that include subunits encoded by organelle and nuclear genomes. In animal cells, compensatory evolution between mitochondrial and nuclear-encoded subunits was identified and the high mitochondrial mutation rates were hypothesized to drive compensatory evolution in nuclear genomes. In plant cells, compensatory evolution between plastid and nucleus has rarely been investigated in a phylogenetic framework. To investigate plastid–nuclear coevolution, we focused on plastid ribosomal protein genes that are encoded by plastid and nuclear genomes from 27 Geraniales species. Substitution rates were compared for five sets of genes representing plastid- and nuclear-encoded ribosomal subunit proteins targeted to the cytosol or the plastid as well as nonribosomal protein controls. We found that nonsynonymous substitution rates (dN) and the ratios of nonsynonymous to synonymous substitution rates (ω) were accelerated in both plastid- (CpRP) and nuclear-encoded subunits (NuCpRP) of the plastid ribosome relative to control sequences. Our analyses revealed strong signals of cytonuclear coevolution between plastid- and nuclear-encoded subunits, in which nonsynonymous substitutions in CpRP and NuCpRP tend to occur along the same branches in the Geraniaceae phylogeny. This coevolution pattern cannot be explained by physical interaction between amino acid residues. The forces driving accelerated coevolution varied with cellular compartment of the sequence. Increased ω in CpRP was mainly due to intensified positive selection whereas increased ω in NuCpRP was caused by relaxed purifying selection. In addition, the many indels identified in plastid rRNA genes in Geraniaceae may have contributed to changes in plastid subunits. PMID:27190001

  11. Sequence analysis of serum albumins reveals the molecular evolution of ligand recognition properties.

    PubMed

    Fanali, Gabriella; Ascenzi, Paolo; Bernardi, Giorgio; Fasano, Mauro

    2012-01-01

    Serum albumin (SA) is a circulating protein providing a depot and carrier for many endogenous and exogenous compounds. At least seven major binding sites have been identified by structural and functional investigations mainly in human SA. SA is conserved in vertebrates, with at least 49 entries in protein sequence databases. The multiple sequence analysis of this set of entries leads to the definition of a cladistic tree for the molecular evolution of SA orthologs in vertebrates, thus showing the clustering of the considered species, with lamprey SAs (Lethenteron japonicum and Petromyzon marinus) in a separate outgroup. Sequence analysis aimed at searching conserved domains revealed that most SA sequences are made up by three repeated domains (about 600 residues), as extensively characterized for human SA. On the contrary, lamprey SAs are giant proteins (about 1400 residues) comprising seven repeated domains. The phylogenetic analysis of the SA family reveals a stringent correlation with the taxonomic classification of the species available in sequence databases. A focused inspection of the sequences of ligand binding sites in SA revealed that in all sites most residues involved in ligand binding are conserved, although the versatility towards different ligands could be peculiar of higher organisms. Moreover, the analysis of molecular links between the different sites suggests that allosteric modulation mechanisms could be restricted to higher vertebrates.

  12. Increasing genomic diversity and evidence of constrained lifestyle evolution due to insertion sequences in Aeromonas salmonicida.

    PubMed

    Vincent, Antony T; Trudel, Mélanie V; Freschi, Luca; Nagar, Vandan; Gagné-Thivierge, Cynthia; Levesque, Roger C; Charette, Steve J

    2016-01-12

    Aeromonads make up a group of Gram-negative bacteria that includes human and fish pathogens. The Aeromonas salmonicida species has the peculiarity of including five known subspecies. However, few studies of the genomes of A. salmonicida subspecies have been reported to date. We sequenced the genomes of additional A. salmonicida isolates, including three from India, using next-generation sequencing in order to gain a better understanding of the genomic and phylogenetic links between A. salmonicida subspecies. Their relative phylogenetic positions were confirmed by a core genome phylogeny based on 1645 gene sequences. The Indian isolates, which formed a sub-group together with A. salmonicida subsp. pectinolytica, were able to grow at either at 18 °C and 37 °C, unlike the A. salmonicida psychrophilic isolates that did not grow at 37 °C. Amino acid frequencies, GC content, tRNA composition, loss and gain of genes during evolution, pseudogenes as well as genes under positive selection and the mobilome were studied to explain this intraspecies dichotomy. Insertion sequences appeared to be an important driving force that locked the psychrophilic strains into their particular lifestyle in order to conserve their genomic integrity. This observation, based on comparative genomics, is in agreement with previous results showing that insertion sequence mobility induced by heat in A. salmonicida subspecies causes genomic plasticity, resulting in a deleterious effect on the virulence of the bacterium. We provide a proof-of-concept that selfish DNAs play a major role in the evolution of bacterial species by modeling genomes.

  13. POST-MAIN SEQUENCE EVOLUTION OF ICY MINOR PLANETS: IMPLICATIONS FOR WATER RETENTION AND WHITE DWARF POLLUTION

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Malamud, Uri; Perets, Hagai B., E-mail: uri.mal@tx.technion.ac.il, E-mail: hperets@physics.technion.ac.il

    Most observations of polluted white dwarf atmospheres are consistent with accretion of water-depleted planetary material. Among tens of known cases, merely two involve accretion of objects that contain a considerable mass fraction of water. The purpose of this study is to investigate the relative scarcity of these detections. Based on a new and highly detailed model, we evaluate the retention of water inside icy minor planets during the high-luminosity stellar evolution that follows the main sequence. Our model fully considers the thermal, physical, and chemical evolution of icy bodies, following their internal differentiation as well as water depletion, from themore » moment of their birth and through all stellar evolution phases preceding the formation of the white dwarf. We also account for different initial compositions and formation times. Our results differ from previous studies, which have either underestimated or overestimated water retention. We show that water can survive in a variety of circumstances and in great quantities, and therefore other possibilities are discussed in order to explain the infrequency of water detection. We predict that the sequence of accretion is such that water accretes earlier, and more rapidly, than the rest of the silicate disk, considerably reducing the chance of its detection in H-dominated atmospheres. In He-dominated atmospheres, the scarcity of water detections could be observationally biased. It implies that the accreted material is typically intrinsically dry, which may be the result of the inside-out depopulation sequence of minor planets.« less

  14. Sequencing papaya X and Yh chromosomes reveals molecular basis of incipient sex chromosome evolution

    PubMed Central

    Wang, Jianping; Na, Jong-Kuk; Yu, Qingyi; Gschwend, Andrea R.; Han, Jennifer; Zeng, Fanchang; Aryal, Rishi; VanBuren, Robert; Murray, Jan E.; Zhang, Wenli; Navajas-Pérez, Rafael; Feltus, F. Alex; Lemke, Cornelia; Tong, Eric J.; Chen, Cuixia; Man Wai, Ching; Singh, Ratnesh; Wang, Ming-Li; Min, Xiang Jia; Alam, Maqsudul; Charlesworth, Deborah; Moore, Paul H.; Jiang, Jiming; Paterson, Andrew H.; Ming, Ray

    2012-01-01

    Sex determination in papaya is controlled by a recently evolved XY chromosome pair, with two slightly different Y chromosomes controlling the development of males (Y) and hermaphrodites (Yh). To study the events of early sex chromosome evolution, we sequenced the hermaphrodite-specific region of the Yh chromosome (HSY) and its X counterpart, yielding an 8.1-megabase (Mb) HSY pseudomolecule, and a 3.5-Mb sequence for the corresponding X region. The HSY is larger than the X region, mostly due to retrotransposon insertions. The papaya HSY differs from the X region by two large-scale inversions, the first of which likely caused the recombination suppression between the X and Yh chromosomes, followed by numerous additional chromosomal rearrangements. Altogether, including the X and/or HSY regions, 124 transcription units were annotated, including 50 functional pairs present in both the X and HSY. Ten HSY genes had functional homologs elsewhere in the papaya autosomal regions, suggesting movement of genes onto the HSY, whereas the X region had none. Sequence divergence between 70 transcripts shared by the X and HSY revealed two evolutionary strata in the X chromosome, corresponding to the two inversions on the HSY, the older of which evolved about 7.0 million years ago. Gene content differences between the HSY and X are greatest in the older stratum, whereas the gene content and order of the collinear regions are identical. Our findings support theoretical models of early sex chromosome evolution. PMID:22869747

  15. Sequencing papaya X and Yh chromosomes reveals molecular basis of incipient sex chromosome evolution.

    PubMed

    Wang, Jianping; Na, Jong-Kuk; Yu, Qingyi; Gschwend, Andrea R; Han, Jennifer; Zeng, Fanchang; Aryal, Rishi; VanBuren, Robert; Murray, Jan E; Zhang, Wenli; Navajas-Pérez, Rafael; Feltus, F Alex; Lemke, Cornelia; Tong, Eric J; Chen, Cuixia; Wai, Ching Man; Singh, Ratnesh; Wang, Ming-Li; Min, Xiang Jia; Alam, Maqsudul; Charlesworth, Deborah; Moore, Paul H; Jiang, Jiming; Paterson, Andrew H; Ming, Ray

    2012-08-21

    Sex determination in papaya is controlled by a recently evolved XY chromosome pair, with two slightly different Y chromosomes controlling the development of males (Y) and hermaphrodites (Y(h)). To study the events of early sex chromosome evolution, we sequenced the hermaphrodite-specific region of the Y(h) chromosome (HSY) and its X counterpart, yielding an 8.1-megabase (Mb) HSY pseudomolecule, and a 3.5-Mb sequence for the corresponding X region. The HSY is larger than the X region, mostly due to retrotransposon insertions. The papaya HSY differs from the X region by two large-scale inversions, the first of which likely caused the recombination suppression between the X and Y(h) chromosomes, followed by numerous additional chromosomal rearrangements. Altogether, including the X and/or HSY regions, 124 transcription units were annotated, including 50 functional pairs present in both the X and HSY. Ten HSY genes had functional homologs elsewhere in the papaya autosomal regions, suggesting movement of genes onto the HSY, whereas the X region had none. Sequence divergence between 70 transcripts shared by the X and HSY revealed two evolutionary strata in the X chromosome, corresponding to the two inversions on the HSY, the older of which evolved about 7.0 million years ago. Gene content differences between the HSY and X are greatest in the older stratum, whereas the gene content and order of the collinear regions are identical. Our findings support theoretical models of early sex chromosome evolution.

  16. Artificial seismic acceleration

    USGS Publications Warehouse

    Felzer, Karen R.; Page, Morgan T.; Michael, Andrew J.

    2015-01-01

    In their 2013 paper, Bouchon, Durand, Marsan, Karabulut, 3 and Schmittbuhl (BDMKS) claim to see significant accelerating seismicity before M 6.5 interplate mainshocks, but not before intraplate mainshocks, reflecting a preparatory process before large events. We concur with the finding of BDMKS that their interplate dataset has significantly more fore- shocks than their intraplate dataset; however, we disagree that the foreshocks are predictive of large events in particular. Acceleration in stacked foreshock sequences has been seen before and has been explained by the cascade model, in which earthquakes occasionally trigger aftershocks larger than themselves4. In this model, the time lags between the smaller mainshocks and larger aftershocks follow the inverse power law common to all aftershock sequences, creating an apparent acceleration when stacked (see Supplementary Information).

  17. Accelerating Aerobic Sludge Granulation by Adding Dry Sewage Sludge Micropowder in Sequencing Batch Reactors

    PubMed Central

    Li, Jun; Liu, Jun; Wang, Danjun; Chen, Tao; Ma, Ting; Wang, Zhihong; Zhuo, Weilong

    2015-01-01

    Micropowder (20–250 µm) made from ground dry waste sludge from a municipal sewage treatment plant was added in a sequencing batch reactor (R2), which was fed by synthetic wastewater with acetate as carbon source. Compared with the traditional SBR (R1), aerobic sludge granulation time was shortened 15 days in R2. Furthermore, filamentous bacteria in bulking sludge were controlled to accelerate aerobic granulation and form large granules. Correspondingly, the SVI decreased from 225 mL/g to 37 mL/g. X-ray Fluorescence (XRF) analysis demonstrated that Al and Si from the micropowder were accumulated in granules. A mechanism hypotheses for the acceleration of aerobic granulation by adding dry sludge micropowder is proposed: added micropowder acts as nuclei to induce bacterial attachment; dissolved matters from the micropowder increase abruptly the organic load for starved sludge to control overgrown filamentous bacteria as a framework for aggregation; increased friction from the movement of micropowder forces the filaments which extend outwards to shrink for shaping granules. PMID:26308025

  18. Rapid sequencing of the bamboo mitochondrial genome using Illumina technology and parallel episodic evolution of organelle genomes in grasses.

    PubMed

    Ma, Peng-Fei; Guo, Zhen-Hua; Li, De-Zhu

    2012-01-01

    Compared to their counterparts in animals, the mitochondrial (mt) genomes of angiosperms exhibit a number of unique features. However, unravelling their evolution is hindered by the few completed genomes, of which are essentially Sanger sequenced. While next-generation sequencing technologies have revolutionized chloroplast genome sequencing, they are just beginning to be applied to angiosperm mt genomes. Chloroplast genomes of grasses (Poaceae) have undergone episodic evolution and the evolutionary rate was suggested to be correlated between chloroplast and mt genomes in Poaceae. It is interesting to investigate whether correlated rate change also occurred in grass mt genomes as expected under lineage effects. A time-calibrated phylogenetic tree is needed to examine rate change. We determined a largely completed mt genome from a bamboo, Ferrocalamus rimosivaginus (Poaceae), through Illumina sequencing of total DNA. With combination of de novo and reference-guided assembly, 39.5-fold coverage Illumina reads were finally assembled into scaffolds totalling 432,839 bp. The assembled genome contains nearly the same genes as the completed mt genomes in Poaceae. For examining evolutionary rate in grass mt genomes, we reconstructed a phylogenetic tree including 22 taxa based on 31 mt genes. The topology of the well-resolved tree was almost identical to that inferred from chloroplast genome with only minor difference. The inconsistency possibly derived from long branch attraction in mtDNA tree. By calculating absolute substitution rates, we found significant rate change (∼4-fold) in mt genome before and after the diversification of Poaceae both in synonymous and nonsynonymous terms. Furthermore, the rate change was correlated with that of chloroplast genomes in grasses. Our result demonstrates that it is a rapid and efficient approach to obtain angiosperm mt genome sequences using Illumina sequencing technology. The parallel episodic evolution of mt and chloroplast

  19. Rapid Sequencing of the Bamboo Mitochondrial Genome Using Illumina Technology and Parallel Episodic Evolution of Organelle Genomes in Grasses

    PubMed Central

    Ma, Peng-Fei; Guo, Zhen-Hua; Li, De-Zhu

    2012-01-01

    Background Compared to their counterparts in animals, the mitochondrial (mt) genomes of angiosperms exhibit a number of unique features. However, unravelling their evolution is hindered by the few completed genomes, of which are essentially Sanger sequenced. While next-generation sequencing technologies have revolutionized chloroplast genome sequencing, they are just beginning to be applied to angiosperm mt genomes. Chloroplast genomes of grasses (Poaceae) have undergone episodic evolution and the evolutionary rate was suggested to be correlated between chloroplast and mt genomes in Poaceae. It is interesting to investigate whether correlated rate change also occurred in grass mt genomes as expected under lineage effects. A time-calibrated phylogenetic tree is needed to examine rate change. Methodology/Principal Findings We determined a largely completed mt genome from a bamboo, Ferrocalamus rimosivaginus (Poaceae), through Illumina sequencing of total DNA. With combination of de novo and reference-guided assembly, 39.5-fold coverage Illumina reads were finally assembled into scaffolds totalling 432,839 bp. The assembled genome contains nearly the same genes as the completed mt genomes in Poaceae. For examining evolutionary rate in grass mt genomes, we reconstructed a phylogenetic tree including 22 taxa based on 31 mt genes. The topology of the well-resolved tree was almost identical to that inferred from chloroplast genome with only minor difference. The inconsistency possibly derived from long branch attraction in mtDNA tree. By calculating absolute substitution rates, we found significant rate change (∼4-fold) in mt genome before and after the diversification of Poaceae both in synonymous and nonsynonymous terms. Furthermore, the rate change was correlated with that of chloroplast genomes in grasses. Conclusions/Significance Our result demonstrates that it is a rapid and efficient approach to obtain angiosperm mt genome sequences using Illumina sequencing

  20. Next Generation Sequencing Technology and Genomewide Data Analysis: Perspectives for Retinal Research

    PubMed Central

    Chaitankar, Vijender; Karakülah, Gökhan; Ratnapriya, Rinki; Giuste, Felipe O.; Brooks, Matthew J.; Swaroop, Anand

    2016-01-01

    The advent of high throughput next generation sequencing (NGS) has accelerated the pace of discovery of disease-associated genetic variants and genomewide profiling of expressed sequences and epigenetic marks, thereby permitting systems-based analyses of ocular development and disease. Rapid evolution of NGS and associated methodologies presents significant challenges in acquisition, management, and analysis of large data sets and for extracting biologically or clinically relevant information. Here we illustrate the basic design of commonly used NGS-based methods, specifically whole exome sequencing, transcriptome, and epigenome profiling, and provide recommendations for data analyses. We briefly discuss systems biology approaches for integrating multiple data sets to elucidate gene regulatory or disease networks. While we provide examples from the retina, the NGS guidelines reviewed here are applicable to other tissues/cell types as well. PMID:27297499

  1. Sequence Evolution and Expression Regulation of Stress-Responsive Genes in Natural Populations of Wild Tomato

    PubMed Central

    Fischer, Iris; Steige, Kim A.; Stephan, Wolfgang; Mboup, Mamadou

    2013-01-01

    The wild tomato species Solanum chilense and S. peruvianum are a valuable non-model system for studying plant adaptation since they grow in diverse environments facing many abiotic constraints. Here we investigate the sequence evolution of regulatory regions of drought and cold responsive genes and their expression regulation. The coding regions of these genes were previously shown to exhibit signatures of positive selection. Expression profiles and sequence evolution of regulatory regions of members of the Asr (ABA/water stress/ripening induced) gene family and the dehydrin gene pLC30-15 were analyzed in wild tomato populations from contrasting environments. For S. chilense, we found that Asr4 and pLC30-15 appear to respond much faster to drought conditions in accessions from very dry environments than accessions from more mesic locations. Sequence analysis suggests that the promoter of Asr2 and the downstream region of pLC30-15 are under positive selection in some local populations of S. chilense. By investigating gene expression differences at the population level we provide further support of our previous conclusions that Asr2, Asr4, and pLC30-15 are promising candidates for functional studies of adaptation. Our analysis also demonstrates the power of the candidate gene approach in evolutionary biology research and highlights the importance of wild Solanum species as a genetic resource for their cultivated relatives. PMID:24205149

  2. Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

    PubMed Central

    Varela, Ignacio; Fisher, Rosalie; McGranahan, Nicholas; Matthews, Nicholas; Santos, Claudio R; Martinez, Pierre; Phillimore, Benjamin; Begum, Sharmin; Rabinowitz, Adam; Spencer-Dene, Bradley; Gulati, Sakshi; Bates, Paul A; Stamp, Gordon; Pickering, Lisa; Gore, Martin; Nicol, David L; Hazell, Steven; Futreal, P Andrew; Stewart, Aengus; Swanton, Charles

    2015-01-01

    Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development. PMID:24487277

  3. Turbulence Evolution and Shock Acceleration of Solar Energetic Particles

    NASA Technical Reports Server (NTRS)

    Chee, Ng K.

    2007-01-01

    We model the effects of self-excitation/damping and shock transmission of Alfven waves on solar-energetic-particle (SEP) acceleration at a coronal-mass-ejection (CME) driven parallel shock. SEP-excited outward upstream waves speedily bootstrap acceleration. Shock transmission further raises the SEP-excited wave intensities at high wavenumbers but lowers them at low wavenumbers through wavenumber shift. Downstream, SEP excitation of inward waves and damping of outward waves tend to slow acceleration. Nevertheless, > 2000 km/s parallel shocks at approx. 3.5 solar radii can accelerate SEPs to 100 MeV in < 5 minutes.

  4. Analysis of Complete Nucleotide Sequences of 12 Gossypium Chloroplast Genomes: Origin and Evolution of Allotetraploids

    PubMed Central

    Xu, Qin; Xiong, Guanjun; Li, Pengbo; He, Fei; Huang, Yi; Wang, Kunbo; Li, Zhaohu; Hua, Jinping

    2012-01-01

    Background Cotton (Gossypium spp.) is a model system for the analysis of polyploidization. Although ascertaining the donor species of allotetraploid cotton has been intensively studied, sequence comparison of Gossypium chloroplast genomes is still of interest to understand the mechanisms underlining the evolution of Gossypium allotetraploids, while it is generally accepted that the parents were A- and D-genome containing species. Here we performed a comparative analysis of 13 Gossypium chloroplast genomes, twelve of which are presented here for the first time. Methodology/Principal Findings The size of 12 chloroplast genomes under study varied from 159,959 bp to 160,433 bp. The chromosomes were highly similar having >98% sequence identity. They encoded the same set of 112 unique genes which occurred in a uniform order with only slightly different boundary junctions. Divergence due to indels as well as substitutions was examined separately for genome, coding and noncoding sequences. The genome divergence was estimated as 0.374% to 0.583% between allotetraploid species and A-genome, and 0.159% to 0.454% within allotetraploids. Forty protein-coding genes were completely identical at the protein level, and 20 intergenic sequences were completely conserved. The 9 allotetraploids shared 5 insertions and 9 deletions in whole genome, and 7-bp substitutions in protein-coding genes. The phylogenetic tree confirmed a close relationship between allotetraploids and the ancestor of A-genome, and the allotetraploids were divided into four separate groups. Progenitor allotetraploid cotton originated 0.43–0.68 million years ago (MYA). Conclusion Despite high degree of conservation between the Gossypium chloroplast genomes, sequence variations among species could still be detected. Gossypium chloroplast genomes preferred for 5-bp indels and 1–3-bp indels are mainly attributed to the SSR polymorphisms. This study supports that the common ancestor of diploid A-genome species in

  5. Massive Thermal Acceleration of the Emergence of Primordial Chemistry, the Incidence of Spontaneous Mutation, and the Evolution of Enzymes*

    PubMed Central

    Wolfenden, Richard

    2014-01-01

    Kelvin considered it unlikely that sufficient time had elapsed on the earth for life to have reached its present level of complexity. In the warm surroundings in which life first appeared, however, elevated temperatures would have reduced the kinetic barriers to reaction. Recent experiments disclose the profound extent to which very slow reactions are accelerated by elevated temperatures, collapsing the time that would have been required for early events in primordial chemistry before the advent of enzymes. If a primitive enzyme, like model catalysts and most modern enzymes, accelerated a reaction by lowering its enthalpy of activation, then the rate enhancement that it produced would have increased automatically as the environment cooled, quite apart from any improvements in catalytic activity that arose from mutation and natural selection. The chemical events responsible for spontaneous mutation are also highly sensitive to temperature, furnishing an independent mechanism for accelerating evolution. PMID:25210030

  6. The consequences of sequence erosion in the evolution of recombination hotspots.

    PubMed

    Tiemann-Boege, Irene; Schwarz, Theresa; Striedner, Yasmin; Heissl, Angelika

    2017-12-19

    Meiosis is initiated by a double-strand break (DSB) introduced in the DNA by a highly controlled process that is repaired by recombination. In many organisms, recombination occurs at specific and narrow regions of the genome, known as recombination hotspots, which overlap with regions enriched for DSBs. In recent years, it has been demonstrated that conversions and mutations resulting from the repair of DSBs lead to a rapid sequence evolution at recombination hotspots eroding target sites for DSBs. We still do not fully understand the effect of this erosion in the recombination activity, but evidence has shown that the binding of trans -acting factors like PRDM9 is affected. PRDM9 is a meiosis-specific, multi-domain protein that recognizes DNA target motifs by its zinc finger domain and directs DSBs to these target sites. Here we discuss the changes in affinity of PRDM9 to eroded recognition sequences, and explain how these changes in affinity of PRDM9 can affect recombination, leading sometimes to sterility in the context of hybrid crosses. We also present experimental data showing that DNA methylation reduces PRDM9 binding in vitro Finally, we discuss PRDM9-independent hotspots, posing the question how these hotspots evolve and change with sequence erosion.This article is part of the themed issue 'Evolutionary causes and consequences of recombination rate variation in sexual organisms'. © 2017 The Authors.

  7. The consequences of sequence erosion in the evolution of recombination hotspots

    PubMed Central

    Schwarz, Theresa; Heissl, Angelika

    2017-01-01

    Meiosis is initiated by a double-strand break (DSB) introduced in the DNA by a highly controlled process that is repaired by recombination. In many organisms, recombination occurs at specific and narrow regions of the genome, known as recombination hotspots, which overlap with regions enriched for DSBs. In recent years, it has been demonstrated that conversions and mutations resulting from the repair of DSBs lead to a rapid sequence evolution at recombination hotspots eroding target sites for DSBs. We still do not fully understand the effect of this erosion in the recombination activity, but evidence has shown that the binding of trans-acting factors like PRDM9 is affected. PRDM9 is a meiosis-specific, multi-domain protein that recognizes DNA target motifs by its zinc finger domain and directs DSBs to these target sites. Here we discuss the changes in affinity of PRDM9 to eroded recognition sequences, and explain how these changes in affinity of PRDM9 can affect recombination, leading sometimes to sterility in the context of hybrid crosses. We also present experimental data showing that DNA methylation reduces PRDM9 binding in vitro. Finally, we discuss PRDM9-independent hotspots, posing the question how these hotspots evolve and change with sequence erosion. This article is part of the themed issue ‘Evolutionary causes and consequences of recombination rate variation in sexual organisms’. PMID:29109225

  8. Silencing Effect of Hominoid Highly Conserved Noncoding Sequences on Embryonic Brain Development

    PubMed Central

    Mahmoudi Saber, Morteza

    2017-01-01

    Abstract Superfamily Hominoidea, which consists of Hominidae (humans and great apes) and Hylobatidae (gibbons), is well-known for sharing human-like characteristics, however, the genomic origins of these shared unique phenotypes have mainly remained elusive. To decipher the underlying genomic basis of Hominoidea-restricted phenotypes, we identified and characterized Hominoidea-restricted highly conserved noncoding sequences (HCNSs) that are a class of potential regulatory elements which may be involved in evolution of lineage-specific phenotypes. We discovered 679 such HCNSs from human, chimpanzee, gorilla, orangutan and gibbon genomes. These HCNSs were demonstrated to be under purifying selection but with lineage-restricted characteristics different from old CNSs. A significant proportion of their ancestral sequences had accelerated rates of nucleotide substitutions, insertions and deletions during the evolution of common ancestor of Hominoidea, suggesting the intervention of positive Darwinian selection for creating those HCNSs. In contrary to enhancer elements and similar to silencer sequences, these Hominoidea-restricted HCNSs are located in close proximity of transcription start sites. Their target genes are enriched in the nervous system, development and transcription, and they tend to be remotely located from the nearest coding gene. Chip-seq signals and gene expression patterns suggest that Hominoidea-restricted HCNSs are likely to be functional regulatory elements by imposing silencing effects on their target genes in a tissue-restricted manner during fetal brain development. These HCNSs, emerged through adaptive evolution and conserved through purifying selection, represent a set of promising targets for future functional studies of the evolution of Hominoidea-restricted phenotypes. PMID:28633494

  9. Clinical sequencing uncovers origins and evolution of Lassa virus

    PubMed Central

    Andersen, Kristian G.; Shapiro, B. Jesse; Matranga, Christian B.; Sealfon, Rachel; Lin, Aaron E.; Moses, Lina M.; Folarin, Onikepe A.; Goba, Augustine; Odia, Ikponmwonsa; Ehiane, Philomena E.; Momoh, Mambu; England, Eleina M.; Winnicki, Sarah; Branco, Luis M.; Gire, Stephen K.; Phelan, Eric; Tariyal, Ridhi; Tewhey, Ryan; Omoniwa, Omowunmi; Fullah, Mohammed; Fonnie, Richard; Fonnie, Mbalu; Kanneh, Lansana; Jalloh, Simbirie; Gbakie, Michael; Saffa, Sidiki; Karbo, Kandeh; Gladden, Adrianne D.; Qu, James; Stremlau, Matthew; Nekoui, Mahan; Finucane, Hilary K.; Tabrizi, Shervin; Vitti, Joseph J.; Birren, Bruce; Fitzgerald, Michael; McCowan, Caryn; Ireland, Andrea; Berlin, Aaron M.; Bochicchio, James; Tazon-Vega, Barbara; Lennon, Niall J.; Ryan, Elizabeth M.; Bjornson, Zach; Milner, Danny A.; Lukens, Amanda K.; Broodie, Nisha; Rowland, Megan; Heinrich, Megan; Akdag, Marjan; Schieffelin, John S.; Levy, Danielle; Akpan, Henry; Bausch, Daniel G.; Rubins, Kathleen; McCormick, Joseph B.; Lander, Eric S.; Günther, Stephan; Hensley, Lisa; Okogbenin, Sylvanus; Schaffner, Stephen F.; Okokhere, Peter O.; Khan, S. Humarr; Grant, Donald S.; Akpede, George O.; Asogun, Danny A.; Gnirke, Andreas; Levin, Joshua Z.; Happi, Christian T.; Garry, Robert F.; Sabeti, Pardis C.

    2015-01-01

    Summary The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us how little is known about biosafety level-4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. PMID:26276630

  10. Empirical analysis of RNA robustness and evolution using high-throughput sequencing of ribozyme reactions.

    PubMed

    Hayden, Eric J

    2016-08-15

    RNA molecules provide a realistic but tractable model of a genotype to phenotype relationship. This relationship has been extensively investigated computationally using secondary structure prediction algorithms. Enzymatic RNA molecules, or ribozymes, offer access to genotypic and phenotypic information in the laboratory. Advancements in high-throughput sequencing technologies have enabled the analysis of sequences in the lab that now rivals what can be accomplished computationally. This has motivated a resurgence of in vitro selection experiments and opened new doors for the analysis of the distribution of RNA functions in genotype space. A body of computational experiments has investigated the persistence of specific RNA structures despite changes in the primary sequence, and how this mutational robustness can promote adaptations. This article summarizes recent approaches that were designed to investigate the role of mutational robustness during the evolution of RNA molecules in the laboratory, and presents theoretical motivations, experimental methods and approaches to data analysis. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. On Statistical Modeling of Sequencing Noise in High Depth Data to Assess Tumor Evolution

    NASA Astrophysics Data System (ADS)

    Rabadan, Raul; Bhanot, Gyan; Marsilio, Sonia; Chiorazzi, Nicholas; Pasqualucci, Laura; Khiabanian, Hossein

    2018-07-01

    One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate our model with simulated exponentially expanded populations as well as data from cell line and patient sample dilution experiments, demonstrating its utility in prognosticating tumor progression. Our results may have the potential to identify significant mutations that can cause recurrence. These results are relevant in the pretreatment clinical setting to determine appropriate therapy and prepare for potential recurrence pretreatment.

  12. On Statistical Modeling of Sequencing Noise in High Depth Data to Assess Tumor Evolution

    NASA Astrophysics Data System (ADS)

    Rabadan, Raul; Bhanot, Gyan; Marsilio, Sonia; Chiorazzi, Nicholas; Pasqualucci, Laura; Khiabanian, Hossein

    2017-12-01

    One cause of cancer mortality is tumor evolution to therapy-resistant disease. First line therapy often targets the dominant clone, and drug resistance can emerge from preexisting clones that gain fitness through therapy-induced natural selection. Such mutations may be identified using targeted sequencing assays by analysis of noise in high-depth data. Here, we develop a comprehensive, unbiased model for sequencing error background. We find that noise in sufficiently deep DNA sequencing data can be approximated by aggregating negative binomial distributions. Mutations with frequencies above noise may have prognostic value. We evaluate our model with simulated exponentially expanded populations as well as data from cell line and patient sample dilution experiments, demonstrating its utility in prognosticating tumor progression. Our results may have the potential to identify significant mutations that can cause recurrence. These results are relevant in the pretreatment clinical setting to determine appropriate therapy and prepare for potential recurrence pretreatment.

  13. Electron acceleration via magnetic island coalescence

    NASA Astrophysics Data System (ADS)

    Shinohara, I.; Yumura, T.; Tanaka, K. G.; Fujimoto, M.

    2009-06-01

    Electron acceleration via fast magnetic island coalescence that happens as quick magnetic reconnection triggering (QMRT) proceeds has been studied. We have carried out a three-dimensional full kinetic simulation of the Harris current sheet with a large enough simulation run for two magnetic islands coalescence. Due to the strong inductive electric field associated with the non-linear evolution of the lower-hybrid-drift instability and the magnetic island coalescence process observed in the non-linear stage of the collisionless tearing mode, electrons are significantly accelerated at around the neutral sheet and the subsequent X-line. The accelerated meandering electrons generated by the non-linear evolution of the lower-hybrid-drift instability are resulted in QMRT, and QMRT leads to fast magnetic island coalescence. As a whole, the reconnection triggering and its transition to large-scale structure work as an effective electron accelerator.

  14. High-resolution sequence stratigraphy and continental environmental evolution: An example from east-central Argentina

    NASA Astrophysics Data System (ADS)

    Beilinson, Elisa; Veiga, Gonzalo D.; Spalletti, Luis A.

    2013-10-01

    The aims of this contribution is to establish a high-resolution sequence stratigraphic scheme for the continental deposits that constitute the Punta San Andrés Alloformation (Plio-Pleistocene) in east-central Argentina, to analyze the basin fill evolution and to identify and assess the role that extrinsic factors such as climate and sea-level oscillations played during evolution of the unit. For the high-resolution sequence stratigraphical study of the Punta San Andrés Alloformation, high- and low-accommodation system tracts were defined mainly on the basis of the architectural elements present in the succession, also taking into account the relative degree of channel and floodplain deposits. Discontinuities and the nature of depositional systems generated during variations in accommodation helped identify two fourth-order high-accommodation system tracts and two fourth-order low-accommodation system tracts. At a third-order scale, the Punta San Andrés Alloformation may be interpreted as the progradation of continental depositional systems, characterized by a braided system in the proximal areas, and a low-sinuosity, single-channel system in the distal areas, defined by a high rate of sediment supply and discharge peaks which periodically flooded the plains and generated high aggradation rates during the late Pliocene and lower Pleistocene.

  15. Comparative analysis of syntenic genes in grass genomes reveals accelerated rates of gene structure and coding sequence evolution in polyploid wheat

    USDA-ARS?s Scientific Manuscript database

    Cycles of whole genome duplication (WGD) and diploidization are hallmarks of eukaryotic genome evolution and speciation. Polyploid wheat (Triticum aestivum) has had a massive increase in genome size largely due to recent WGDs. How these processes may impact the dynamics of gene evolution was studied...

  16. Biased Gene Conversion and GC-Content Evolution in the Coding Sequences of Reptiles and Vertebrates

    PubMed Central

    Figuet, Emeric; Ballenghien, Marion; Romiguier, Jonathan; Galtier, Nicolas

    2015-01-01

    Mammalian and avian genomes are characterized by a substantial spatial heterogeneity of GC-content, which is often interpreted as reflecting the effect of local GC-biased gene conversion (gBGC), a meiotic repair bias that favors G and C over A and T alleles in high-recombining genomic regions. Surprisingly, the first fully sequenced nonavian sauropsid (i.e., reptile), the green anole Anolis carolinensis, revealed a highly homogeneous genomic GC-content landscape, suggesting the possibility that gBGC might not be at work in this lineage. Here, we analyze GC-content evolution at third-codon positions (GC3) in 44 vertebrates species, including eight newly sequenced transcriptomes, with a specific focus on nonavian sauropsids. We report that reptiles, including the green anole, have a genome-wide distribution of GC3 similar to that of mammals and birds, and we infer a strong GC3-heterogeneity to be already present in the tetrapod ancestor. We further show that the dynamic of coding sequence GC-content is largely governed by karyotypic features in vertebrates, notably in the green anole, in agreement with the gBGC hypothesis. The discrepancy between third-codon positions and noncoding DNA regarding GC-content dynamics in the green anole could not be explained by the activity of transposable elements or selection on codon usage. This analysis highlights the unique value of third-codon positions as an insertion/deletion-free marker of nucleotide substitution biases that ultimately affect the evolution of proteins. PMID:25527834

  17. Inter- and Intraspecies Phylogenetic Analyses Reveal Extensive X–Y Gene Conversion in the Evolution of Gametologous Sequences of Human Sex Chromosomes

    PubMed Central

    Trombetta, Beniamino; Sellitto, Daniele; Scozzari, Rosaria; Cruciani, Fulvio

    2014-01-01

    It has long been believed that the male-specific region of the human Y chromosome (MSY) is genetically independent from the X chromosome. This idea has been recently dismissed due to the discovery that X–Y gametologous gene conversion may occur. However, the pervasiveness of this molecular process in the evolution of sex chromosomes has yet to be exhaustively analyzed. In this study, we explored how pervasive X–Y gene conversion has been during the evolution of the youngest stratum of the human sex chromosomes. By comparing about 0.5 Mb of human–chimpanzee gametologous sequences, we identified 19 regions in which extensive gene conversion has occurred. From our analysis, two major features of these emerged: 1) Several of them are evolutionarily conserved between the two species and 2) almost all of the 19 hotspots overlap with regions where X–Y crossing-over has been previously reported to be involved in sex reversal. Furthermore, in order to explore the dynamics of X–Y gametologous conversion in recent human evolution, we resequenced these 19 hotspots in 68 widely divergent Y haplogroups and used publicly available single nucleotide polymorphism data for the X chromosome. We found that at least ten hotspots are still active in humans. Hence, the results of the interspecific analysis are consistent with the hypothesis of widespread reticulate evolution within gametologous sequences in the differentiation of hominini sex chromosomes. In turn, intraspecific analysis demonstrates that X–Y gene conversion may modulate human sex-chromosome-sequence evolution to a greater extent than previously thought. PMID:24817545

  18. Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized 13C imaging using the bSSFP sequence

    NASA Astrophysics Data System (ADS)

    Milshteyn, Eugene; von Morze, Cornelius; Reed, Galen D.; Shang, Hong; Shin, Peter J.; Larson, Peder E. Z.; Vigneron, Daniel B.

    2018-05-01

    Acceleration of dynamic 2D (T2 Mapping) and 3D hyperpolarized 13C MRI acquisitions using the balanced steady-state free precession sequence was achieved with a specialized reconstruction method, based on the combination of low rank plus sparse and local low rank reconstructions. Methods were validated using both retrospectively and prospectively undersampled in vivo data from normal rats and tumor-bearing mice. Four-fold acceleration of 1-2 mm isotropic 3D dynamic acquisitions with 2-5 s temporal resolution and two-fold acceleration of 0.25-1 mm2 2D dynamic acquisitions was achieved. This enabled visualization of the biodistribution of [2-13C]pyruvate, [1-13C]lactate, [13C, 15N2]urea, and HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of high resolution T2 maps.

  19. Longitudinal Antigenic Sequences and Sites from Intra-Host Evolution (LASSIE) identifies immune-selected HIV variants

    DOE PAGES

    Hraber, Peter; Korber, Bette; Wagh, Kshitij; ...

    2015-10-21

    Within-host genetic sequencing from samples collected over time provides a dynamic view of how viruses evade host immunity. Immune-driven mutations might stimulate neutralization breadth by selecting antibodies adapted to cycles of immune escape that generate within-subject epitope diversity. Comprehensive identification of immune-escape mutations is experimentally and computationally challenging. With current technology, many more viral sequences can readily be obtained than can be tested for binding and neutralization, making down-selection necessary. Typically, this is done manually, by picking variants that represent different time-points and branches on a phylogenetic tree. Such strategies are likely to miss many relevant mutations and combinations ofmore » mutations, and to be redundant for other mutations. Longitudinal Antigenic Sequences and Sites from Intrahost Evolution (LASSIE) uses transmitted founder loss to identify virus “hot-spots” under putative immune selection and chooses sequences that represent recurrent mutations in selected sites. LASSIE favors earliest sequences in which mutations arise. Here, with well-characterized longitudinal Env sequences, we confirmed selected sites were concentrated in antibody contacts and selected sequences represented diverse antigenic phenotypes. Finally, practical applications include rapidly identifying immune targets under selective pressure within a subject, selecting minimal sets of reagents for immunological assays that characterize evolving antibody responses, and for immunogens in polyvalent “cocktail” vaccines.« less

  20. MID-INFRARED EVIDENCE FOR ACCELERATED EVOLUTION IN COMPACT GROUP GALAXIES

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Walker, Lisa May; Johnson, Kelsey E.; Gallagher, Sarah C.

    2010-11-15

    Compact galaxy groups are at the extremes of the group environment, with high number densities and low velocity dispersions that likely affect member galaxy evolution. To explore the impact of this environment in detail, we examine the distribution in the mid-infrared (MIR) 3.6-8.0 {mu}m color space of 42 galaxies from 12 Hickson compact groups (HCGs) in comparison with several control samples, including the LVL+SINGS galaxies, interacting galaxies, and galaxies from the Coma Cluster. We find that the HCG galaxies are strongly bimodal, with statistically significant evidence for a gap in their distribution. In contrast, none of the other samples showmore » such a marked gap, and only galaxies in the Coma infall region have a distribution that is statistically consistent with the HCGs in this parameter space. To further investigate the cause of the HCG gap, we compare the galaxy morphologies of the HCG and LVL+SINGS galaxies, and also probe the specific star formation rate (SSFR) of the HCG galaxies. While galaxy morphology in HCG galaxies is strongly linked to position with MIR color space, the more fundamental property appears to be the SSFR, or star formation rate normalized by stellar mass. We conclude that the unusual MIR color distribution of HCG galaxies is a direct product of their environment, which is most similar to that of the Coma infall region. In both cases, galaxy densities are high, but gas has not been fully processed or stripped. We speculate that the compact group environment fosters accelerated evolution of galaxies from star-forming and neutral gas-rich to quiescent and neutral gas-poor, leaving few members in the MIR gap at any time.« less

  1. The ergot alkaloid gene cluster in Claviceps purpurea: extension of the cluster sequence and intra species evolution.

    PubMed

    Haarmann, Thomas; Machado, Caroline; Lübbe, Yvonne; Correia, Telmo; Schardl, Christopher L; Panaccione, Daniel G; Tudzynski, Paul

    2005-06-01

    The genomic region of Claviceps purpurea strain P1 containing the ergot alkaloid gene cluster [Tudzynski, P., Hölter, K., Correia, T., Arntz, C., Grammel, N., Keller, U., 1999. Evidence for an ergot alkaloid gene cluster in Claviceps purpurea. Mol. Gen. Genet. 261, 133-141] was explored by chromosome walking, and additional genes probably involved in the ergot alkaloid biosynthesis have been identified. The putative cluster sequence (extending over 68.5kb) contains 4 different nonribosomal peptide synthetase (NRPS) genes and several putative oxidases. Northern analysis showed that most of the genes were co-regulated (repressed by high phosphate), and identified probable flanking genes by lack of co-regulation. Comparison of the cluster sequences of strain P1, an ergotamine producer, with that of strain ECC93, an ergocristine producer, showed high conservation of most of the cluster genes, but significant variation in the NRPS modules, strongly suggesting that evolution of these chemical races of C. purpurea is determined by evolution of NRPS module specificity.

  2. Clinical Sequencing Uncovers Origins and Evolution of Lassa Virus.

    PubMed

    Andersen, Kristian G; Shapiro, B Jesse; Matranga, Christian B; Sealfon, Rachel; Lin, Aaron E; Moses, Lina M; Folarin, Onikepe A; Goba, Augustine; Odia, Ikponmwonsa; Ehiane, Philomena E; Momoh, Mambu; England, Eleina M; Winnicki, Sarah; Branco, Luis M; Gire, Stephen K; Phelan, Eric; Tariyal, Ridhi; Tewhey, Ryan; Omoniwa, Omowunmi; Fullah, Mohammed; Fonnie, Richard; Fonnie, Mbalu; Kanneh, Lansana; Jalloh, Simbirie; Gbakie, Michael; Saffa, Sidiki; Karbo, Kandeh; Gladden, Adrianne D; Qu, James; Stremlau, Matthew; Nekoui, Mahan; Finucane, Hilary K; Tabrizi, Shervin; Vitti, Joseph J; Birren, Bruce; Fitzgerald, Michael; McCowan, Caryn; Ireland, Andrea; Berlin, Aaron M; Bochicchio, James; Tazon-Vega, Barbara; Lennon, Niall J; Ryan, Elizabeth M; Bjornson, Zach; Milner, Danny A; Lukens, Amanda K; Broodie, Nisha; Rowland, Megan; Heinrich, Megan; Akdag, Marjan; Schieffelin, John S; Levy, Danielle; Akpan, Henry; Bausch, Daniel G; Rubins, Kathleen; McCormick, Joseph B; Lander, Eric S; Günther, Stephan; Hensley, Lisa; Okogbenin, Sylvanus; Schaffner, Stephen F; Okokhere, Peter O; Khan, S Humarr; Grant, Donald S; Akpede, George O; Asogun, Danny A; Gnirke, Andreas; Levin, Joshua Z; Happi, Christian T; Garry, Robert F; Sabeti, Pardis C

    2015-08-13

    The 2013-2015 West African epidemic of Ebola virus disease (EVD) reminds us of how little is known about biosafety level 4 viruses. Like Ebola virus, Lassa virus (LASV) can cause hemorrhagic fever with high case fatality rates. We generated a genomic catalog of almost 200 LASV sequences from clinical and rodent reservoir samples. We show that whereas the 2013-2015 EVD epidemic is fueled by human-to-human transmissions, LASV infections mainly result from reservoir-to-human infections. We elucidated the spread of LASV across West Africa and show that this migration was accompanied by changes in LASV genome abundance, fatality rates, codon adaptation, and translational efficiency. By investigating intrahost evolution, we found that mutations accumulate in epitopes of viral surface proteins, suggesting selection for immune escape. This catalog will serve as a foundation for the development of vaccines and diagnostics. VIDEO ABSTRACT. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. Emergence and Evolution of Hominidae-Specific Coding and Noncoding Genomic Sequences

    PubMed Central

    Saber, Morteza Mahmoudi; Adeyemi Babarinde, Isaac; Hettiarachchi, Nilmini; Saitou, Naruya

    2016-01-01

    Family Hominidae, which includes humans and great apes, is recognized for unique complex social behavior and intellectual abilities. Despite the increasing genome data, however, the genomic origin of its phenotypic uniqueness has remained elusive. Clade-specific genes and highly conserved noncoding sequences (HCNSs) are among the high-potential evolutionary candidates involved in driving clade-specific characters and phenotypes. On this premise, we analyzed whole genome sequences along with gene orthology data retrieved from major DNA databases to find Hominidae-specific (HS) genes and HCNSs. We discovered that Down syndrome critical region 4 (DSCR4) is the only experimentally verified gene uniquely present in Hominidae. DSCR4 has no structural homology to any known protein and was inferred to have emerged in several steps through LTR/ERV1, LTR/ERVL retrotransposition, and transversion. Using the genomic distance as neutral evolution threshold, we identified 1,658 HS HCNSs. Polymorphism coverage and derived allele frequency analysis of HS HCNSs showed that these HCNSs are under purifying selection, indicating that they may harbor important functions. They are overrepresented in promoters/untranslated regions, in close proximity of genes involved in sensory perception of sound and developmental process, and also showed a significantly lower nucleosome occupancy probability. Interestingly, many ancestral sequences of the HS HCNSs showed very high evolutionary rates. This suggests that new functions emerged through some kind of positive selection, and then purifying selection started to operate to keep these functions. PMID:27289096

  4. CUDAMPF: a multi-tiered parallel framework for accelerating protein sequence search in HMMER on CUDA-enabled GPU.

    PubMed

    Jiang, Hanyu; Ganesan, Narayan

    2016-02-27

    HMMER software suite is widely used for analysis of homologous protein and nucleotide sequences with high sensitivity. The latest version of hmmsearch in HMMER 3.x, utilizes heuristic-pipeline which consists of MSV/SSV (Multiple/Single ungapped Segment Viterbi) stage, P7Viterbi stage and the Forward scoring stage to accelerate homology detection. Since the latest version is highly optimized for performance on modern multi-core CPUs with SSE capabilities, only a few acceleration attempts report speedup. However, the most compute intensive tasks within the pipeline (viz., MSV/SSV and P7Viterbi stages) still stand to benefit from the computational capabilities of massively parallel processors. A Multi-Tiered Parallel Framework (CUDAMPF) implemented on CUDA-enabled GPUs presented here, offers a finer-grained parallelism for MSV/SSV and Viterbi algorithms. We couple SIMT (Single Instruction Multiple Threads) mechanism with SIMD (Single Instructions Multiple Data) video instructions with warp-synchronism to achieve high-throughput processing and eliminate thread idling. We also propose a hardware-aware optimal allocation scheme of scarce resources like on-chip memory and caches in order to boost performance and scalability of CUDAMPF. In addition, runtime compilation via NVRTC available with CUDA 7.0 is incorporated into the presented framework that not only helps unroll innermost loop to yield upto 2 to 3-fold speedup than static compilation but also enables dynamic loading and switching of kernels depending on the query model size, in order to achieve optimal performance. CUDAMPF is designed as a hardware-aware parallel framework for accelerating computational hotspots within the hmmsearch pipeline as well as other sequence alignment applications. It achieves significant speedup by exploiting hierarchical parallelism on single GPU and takes full advantage of limited resources based on their own performance features. In addition to exceeding performance of other

  5. Epoch-based likelihood models reveal no evidence for accelerated evolution of viviparity in squamate reptiles in response to cenozoic climate change.

    PubMed

    King, Benedict; Lee, Michael S Y

    2015-09-01

    A broad scale analysis of the evolution of viviparity across nearly 4,000 species of squamates revealed that origins increase in frequency toward the present, raising the question of whether rates of change have accelerated. We here use simulations to show that the increased frequency is within the range expected given that the number of squamate lineages also increases with time. Novel, epoch-based methods implemented in BEAST (which allow rates of discrete character evolution to vary across time-slices) also give congruent results, with recent epochs having very similar rates to older epochs. Thus, contrary to expectations, there was no accelerated burst of origins of viviparity in response to global cooling during the Cenozoic or glacial cycles during the Plio-Pleistocene. However, if one accepts the conventional view that viviparity is more likely to evolve than to be lost, and also the evidence here that viviparity has evolved with similar regularity throughout the last 200 Ma, then the absence of large, ancient clades of viviparous squamates (analogs to therian mammals) requires explanation. Viviparous squamate lineages might be more prone to extinction than are oviparous lineages, due to their prevalance at high elevations and latitudes and thus greater susceptibility to climate fluctuations. If so, the directional bias in character evolution would be offset by the bias in extinction rates. © 2015 Wiley Periodicals, Inc.

  6. Sequence Comparisons of Odorant Receptors among Tortricid Moths Reveal Different Rates of Molecular Evolution among Family Members

    PubMed Central

    Carraher, Colm; Authier, Astrid; Steinwender, Bernd; Newcomb, Richard D.

    2012-01-01

    In insects, odorant receptors detect volatile cues involved in behaviours such as mate recognition, food location and oviposition. We have investigated the evolution of three odorant receptors from five species within the moth genera Ctenopseustis and Planotrotrix, family Tortricidae, which fall into distinct clades within the odorant receptor multigene family. One receptor is the orthologue of the co-receptor Or83b, now known as Orco (OR2), and encodes the obligate ion channel subunit of the receptor complex. In comparison, the other two receptors, OR1 and OR3, are ligand-binding receptor subunits, activated by volatile compounds produced by plants - methyl salicylate and citral, respectively. Rates of sequence evolution at non-synonymous sites were significantly higher in OR1 compared with OR2 and OR3. Within the dataset OR1 contains 109 variable amino acid positions that are distributed evenly across the entire protein including transmembrane helices, loop regions and termini, while OR2 and OR3 contain 18 and 16 variable sites, respectively. OR2 shows a high level of amino acid conservation as expected due to its essential role in odour detection; however we found unexpected differences in the rate of evolution between two ligand-binding odorant receptors, OR1 and OR3. OR3 shows high sequence conservation suggestive of a conserved role in odour reception, whereas the higher rate of evolution observed in OR1, particularly at non-synonymous sites, may be suggestive of relaxed constraint, perhaps associated with the loss of an ancestral role in sex pheromone reception. PMID:22701634

  7. Using a local low rank plus sparse reconstruction to accelerate dynamic hyperpolarized 13C imaging using the bSSFP sequence.

    PubMed

    Milshteyn, Eugene; von Morze, Cornelius; Reed, Galen D; Shang, Hong; Shin, Peter J; Larson, Peder E Z; Vigneron, Daniel B

    2018-05-01

    Acceleration of dynamic 2D (T 2 Mapping) and 3D hyperpolarized 13 C MRI acquisitions using the balanced steady-state free precession sequence was achieved with a specialized reconstruction method, based on the combination of low rank plus sparse and local low rank reconstructions. Methods were validated using both retrospectively and prospectively undersampled in vivo data from normal rats and tumor-bearing mice. Four-fold acceleration of 1-2 mm isotropic 3D dynamic acquisitions with 2-5 s temporal resolution and two-fold acceleration of 0.25-1 mm 2 2D dynamic acquisitions was achieved. This enabled visualization of the biodistribution of [2- 13 C]pyruvate, [1- 13 C]lactate, [ 13 C,  15 N 2 ]urea, and HP001 within heart, kidneys, vasculature, and tumor, as well as calculation of high resolution T 2 maps. Copyright © 2018 Elsevier Inc. All rights reserved.

  8. CUDA compatible GPU cards as efficient hardware accelerators for Smith-Waterman sequence alignment

    PubMed Central

    Manavski, Svetlin A; Valle, Giorgio

    2008-01-01

    accelerators for sequence alignment. Their performance is better than any alternative available on commodity hardware platforms. The solution presented in this paper allows large scale alignments to be performed at low cost, using the exact Smith-Waterman algorithm instead of the largely adopted heuristic approaches. PMID:18387198

  9. Analysis of in vitro evolution reveals the underlying distribution of catalytic activity among random sequences.

    PubMed

    Pressman, Abe; Moretti, Janina E; Campbell, Gregory W; Müller, Ulrich F; Chen, Irene A

    2017-08-21

    The emergence of catalytic RNA is believed to have been a key event during the origin of life. Understanding how catalytic activity is distributed across random sequences is fundamental to estimating the probability that catalytic sequences would emerge. Here, we analyze the in vitro evolution of triphosphorylating ribozymes and translate their fitnesses into absolute estimates of catalytic activity for hundreds of ribozyme families. The analysis efficiently identified highly active ribozymes and estimated catalytic activity with good accuracy. The evolutionary dynamics follow Fisher's Fundamental Theorem of Natural Selection and a corollary, permitting retrospective inference of the distribution of fitness and activity in the random sequence pool for the first time. The frequency distribution of rate constants appears to be log-normal, with a surprisingly steep dropoff at higher activity, consistent with a mechanism for the emergence of activity as the product of many independent contributions. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  10. Is the Size Evolution of Massive Galaxies Accelerated in Cluster Environments?

    NASA Astrophysics Data System (ADS)

    Wilson, Gillian

    2013-10-01

    At z 1.6 the main progenitors of present-day massive clusters are undergoing rapid collapse, and have the highest rates of galaxy merging and assembly. Recent observational studies have hinted at accelerated galaxy evolution in dense environments at this epoch, including increased merger rates and rapid growth in galaxy size relative to the field. We propose WFC3 G102 spectroscopy and F125W {Broad J} imaging of a sample of four massive spectroscopically-confirmed clusters at z = 1.6. Our primary scientific goal is to leverage the CANDELS Wide Legacy dataset to carry out a head-to-head comparison of the sizes of cluster members relative to the field {as a function of stellar mass and Sersic index}, and quantify the role of environment in the observed rapid evolution in galaxy sizes since z = 2. These clusters are four of the highest significance overdensities in the 50 square degree SWIRE fields, and will evolve over time to have present-day masses similar to Coma. They were detected using IRAC [3.6]-[4.5] color, which identifies galaxy overdensities regardless of optically red or blue color. A heroic ground-based spectroscopic campaign has resulted in 44 spectroscopically-confirmed members. However this sample is heavily biased toward star-forming {SF} galaxies, and WFC3 spectroscopy is essential to definitively determine cluster membership for 200 members, without bias with respect to quiescent or SF type. The F125W {rest-frame V-band} imaging is necessary to measure the sizes and morphologies of cluster members. 17-passband broadband imaging spanning UV, optical, near-IR, Spitzer IR and Herschel far-IR is already in hand.

  11. Accelerated Evolution of the Lyα Luminosity Function at z >~ 7 Revealed by the Subaru Ultra-deep Survey for Lyα Emitters at z = 7.3

    NASA Astrophysics Data System (ADS)

    Konno, Akira; Ouchi, Masami; Ono, Yoshiaki; Shimasaku, Kazuhiro; Shibuya, Takatoshi; Furusawa, Hisanori; Nakajima, Kimihiko; Naito, Yoshiaki; Momose, Rieko; Yuma, Suraphong; Iye, Masanori

    2014-12-01

    We present the ultra-deep Subaru narrowband imaging survey for Lyα emitters (LAEs) at z = 7.3 in the Subaru/XMM-Newton Deep Survey (SXDS) and Cosmic Evolution Survey (COSMOS) fields (~0.5 deg2) with a total integration time of 106 hr. Exploiting our new sharp bandwidth filter, NB101, installed on the Suprime-Cam, we have reached L(Lyα) = 2.4 × 1042 erg s-1 (5σ) for z = 7.3 LAEs, about four times deeper than previous Subaru z >~ 7 studies, which allows us to reliably investigate the evolution of the Lyα luminosity function (LF) for the first time down to the luminosity limit same as those of Subaru z = 3.1-6.6 LAE samples. Surprisingly, we only find three and four LAEs in the SXDS and COSMOS fields, respectively, while one expects a total of ~65 LAEs by our survey in the case of no Lyα LF evolution from z = 6.6 to 7.3. We identify a decrease of the Lyα LF from z = 6.6 to 7.3 at the >90% confidence level from our z = 7.3 Lyα LF with the best-fit Schechter parameters of L*{Lyα } = 2.7+8.0-1.2 × 1042 {erg} {s}-1 and φ * = 3.7+17.6-3.3 × 10-4 {Mpc}-3 for a fixed α = -1.5. Moreover, the evolution of the Lyα LF is clearly accelerated at z > 6.6 beyond the measurement uncertainties including cosmic variance. Because no such accelerated evolution of the UV-continuum LF or the cosmic star formation rate (SFR) is found at z ~ 7, but suggested only at z > 8, this accelerated Lyα LF evolution is explained by physical mechanisms different from a pure SFR decrease but related to the Lyα production and escape in the process of cosmic reionization. Because a simple accelerating increase of intergalactic medium neutral hydrogen absorbing Lyα cannot be reconciled with Thomson scattering of optical depth measurements from WMAP and Planck, our findings may support new physical pictures suggested by recent theoretical studies, such as the existence of HI clumpy clouds within cosmic ionized bubbles that are selectively absorbing Lyα and the large ionizing photon escape

  12. Accelerated Evolution in Distinctive Species Reveals Candidate Elements for Clinically Relevant Traits, Including Mutation and Cancer Resistance.

    PubMed

    Ferris, Elliott; Abegglen, Lisa M; Schiffman, Joshua D; Gregg, Christopher

    2018-03-06

    The identity of most functional elements in the mammalian genome and the phenotypes they impact are unclear. Here, we perform a genome-wide comparative analysis of patterns of accelerated evolution in species with highly distinctive traits to discover candidate functional elements for clinically important phenotypes. We identify accelerated regions (ARs) in the elephant, hibernating bat, orca, dolphin, naked mole rat, and thirteen-lined ground squirrel lineages in mammalian conserved regions, uncovering ∼33,000 elements that bind hundreds of different regulatory proteins in humans and mice. ARs in the elephant, the largest land mammal, are uniquely enriched near elephant DNA damage response genes. The genomic hotspot for elephant ARs is the E3 ligase subunit of the Fanconi anemia complex, a master regulator of DNA repair. Additionally, ARs in the six species are associated with specific human clinical phenotypes that have apparent concordance with overt traits in each species. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Genome Sequences of Marine Shrimp Exopalaemon carinicauda Holthuis Provide Insights into Genome Size Evolution of Caridea.

    PubMed

    Yuan, Jianbo; Gao, Yi; Zhang, Xiaojun; Wei, Jiankai; Liu, Chengzhang; Li, Fuhua; Xiang, Jianhai

    2017-07-05

    Crustacea, particularly Decapoda, contains many economically important species, such as shrimps and crabs. Crustaceans exhibit enormous (nearly 500-fold) variability in genome size. However, limited genome resources are available for investigating these species. Exopalaemon carinicauda Holthuis, an economical caridean shrimp, is a potential ideal experimental animal for research on crustaceans. In this study, we performed low-coverage sequencing and de novo assembly of the E. carinicauda genome. The assembly covers more than 95% of coding regions. E. carinicauda possesses a large complex genome (5.73 Gb), with size twice higher than those of many decapod shrimps. As such, comparative genomic analyses were implied to investigate factors affecting genome size evolution of decapods. However, clues associated with genome duplication were not identified, and few horizontally transferred sequences were detected. Ultimately, the burst of transposable elements, especially retrotransposons, was determined as the major factor influencing genome expansion. A total of 2 Gb repeats were identified, and RTE-BovB, Jockey, Gypsy, and DIRS were the four major retrotransposons that significantly expanded. Both recent (Jockey and Gypsy) and ancestral (DIRS) originated retrotransposons responsible for the genome evolution. The E. carinicauda genome also exhibited potential for the genomic and experimental research of shrimps.

  14. Comparing an accelerated 3D fast spin-echo sequence (CS-SPACE) for knee 3-T magnetic resonance imaging with traditional 3D fast spin-echo (SPACE) and routine 2D sequences.

    PubMed

    Altahawi, Faysal F; Blount, Kevin J; Morley, Nicholas P; Raithel, Esther; Omar, Imran M

    2017-01-01

    To compare a faster, new, high-resolution accelerated 3D-fast-spin-echo (3D-FSE) acquisition sequence (CS-SPACE) to traditional 2D and high-resolution 3D sequences for knee 3-T magnetic resonance imaging (MRI). Twenty patients received knee MRIs that included routine 2D (T1, PD ± FS, T2-FS; 0.5 × 0.5 × 3 mm 3 ; ∼10 min), traditional 3D FSE (SPACE-PD-FS; 0.5 × 0.5 × 0.5 mm 3 ; ∼7.5 min), and accelerated 3D-FSE prototype (CS-SPACE-PD-FS; 0.5 × 0.5 × 0.5 mm 3 ; ∼5 min) acquisitions on a 3-T MRI system (Siemens MAGNETOM Skyra). Three musculoskeletal radiologists (MSKRs) prospectively and independently reviewed the studies with graded surveys comparing image and diagnostic quality. Tissue-specific signal-to-noise ratios (SNR) and contrast-to-noise ratios (CNR) were also compared. MSKR-perceived diagnostic quality of cartilage was significantly higher for CS-SPACE than for SPACE and 2D sequences (p < 0.001). Assessment of diagnostic quality of menisci and synovial fluid was higher for CS-SPACE than for SPACE (p < 0.001). CS-SPACE was not significantly different from SPACE but had lower assessments than 2D sequences for evaluation of bones, ligaments, muscles, and fat (p ≤ 0.004). 3D sequences had higher spatial resolution, but lower overall assessed contrast (p < 0.001). Overall image quality from CS-SPACE was assessed as higher than SPACE (p = 0.007), but lower than 2D sequences (p < 0.001). Compared to SPACE, CS-SPACE had higher fluid SNR and CNR against all other tissues (all p < 0.001). The CS-SPACE prototype allows for faster isotropic acquisitions of knee MRIs over currently used protocols. High fluid-to-cartilage CNR and higher spatial resolution over routine 2D sequences may present a valuable role for CS-SPACE in the evaluation of cartilage and menisci.

  15. Evolution of sequence-defined highly functionalized nucleic acid polymers

    NASA Astrophysics Data System (ADS)

    Chen, Zhen; Lichtor, Phillip A.; Berliner, Adrian P.; Chen, Jonathan C.; Liu, David R.

    2018-03-01

    The evolution of sequence-defined synthetic polymers made of building blocks beyond those compatible with polymerase enzymes or the ribosome has the potential to generate new classes of receptors, catalysts and materials. Here we describe a ligase-mediated DNA-templated polymerization and in vitro selection system to evolve highly functionalized nucleic acid polymers (HFNAPs) made from 32 building blocks that contain eight chemically diverse side chains on a DNA backbone. Through iterated cycles of polymer translation, selection and reverse translation, we discovered HFNAPs that bind proprotein convertase subtilisin/kexin type 9 (PCSK9) and interleukin-6, two protein targets implicated in human diseases. Mutation and reselection of an active PCSK9-binding polymer yielded evolved polymers with high affinity (KD = 3 nM). This evolved polymer potently inhibited the binding between PCSK9 and the low-density lipoprotein receptor. Structure-activity relationship studies revealed that specific side chains at defined positions in the polymers are required for binding to their respective targets. Our findings expand the chemical space of evolvable polymers to include densely functionalized nucleic acids with diverse, researcher-defined chemical repertoires.

  16. Evolution of green plants as deduced from 5S rRNA sequences.

    PubMed

    Hori, H; Lim, B L; Osawa, S

    1985-02-01

    We have constructed a phylogenic tree for green plants by comparing 5S rRNA sequences. The tree suggests that the emergence of most of the uni- and multicellular green algae such as Chlamydomonas, Spirogyra, Ulva, and Chlorella occurred in the early stage of green plant evolution. The branching point of Nitella is a little earlier than that of land plants and much later than that of the above green algae, supporting the view that Nitella-like green algae may be the direct precursor to land plants. The Bryophyta and the Pteridophyta separated from each other after emergence of the Spermatophyta. The result is consistent with the view that the Bryophyta evolved from ferns by degeneration. In the Pteridophyta, Psilotum (whisk fern) separated first, and a little later Lycopodium (club moss) separated from the ancestor common to Equisetum (horsetail) and Dryopteris (fern). This order is in accordance with the classical view. During the Spermatophyta evolution, the gymnosperms (Cycas, Ginkgo, and Metasequoia have been studied here) and the angiosperms (flowering plants) separated, and this was followed by the separation of Metasequoia and Cycas (cycad)/Ginkgo (maidenhair tree) on one branch and various flowering plants on the other.

  17. Evolution of green plants as deduced from 5S rRNA sequences

    PubMed Central

    Hori, Hiroshi; Lim, Byung-Lak; Osawa, Syozo

    1985-01-01

    We have constructed a phylogenic tree for green plants by comparing 5S rRNA sequences. The tree suggests that the emergence of most of the uni- and multicellular green algae such as Chlamydomonas, Spirogyra, Ulva, and Chlorella occurred in the early stage of green plant evolution. The branching point of Nitella is a little earlier than that of land plants and much later than that of the above green algae, supporting the view that Nitella-like green algae may be the direct precursor to land plants. The Bryophyta and the Pteridophyta separated from each other after emergence of the Spermatophyta. The result is consistent with the view that the Bryophyta evolved from ferns by degeneration. In the Pteridophyta, Psilotum (whisk fern) separated first, and a little later Lycopodium (club moss) separated from the ancestor common to Equisetum (horsetail) and Dryopteris (fern). This order is in accordance with the classical view. During the Spermatophyta evolution, the gymnosperms (Cycas, Ginkgo, and Metasequoia have been studied here) and the angiosperms (flowering plants) separated, and this was followed by the separation of Metasequoia and Cycas (cycad)/Ginkgo (maidenhair tree) on one branch and various flowering plants on the other. PMID:16593540

  18. The evolution and population structure of Lactobacillus fermentum from different naturally fermented products as determined by multilocus sequence typing (MLST).

    PubMed

    Dan, Tong; Liu, Wenjun; Song, Yuqin; Xu, Haiyan; Menghe, Bilige; Zhang, Heping; Sun, Zhihong

    2015-05-20

    Lactobacillus fermentum is economically important in the production and preservation of fermented foods. A repeatable and discriminative typing method was devised to characterize L. fermentum at the molecular level. The multilocus sequence typing (MLST) scheme developed was based on analysis of the internal sequence of 11 housekeeping gene fragments (clpX, dnaA, dnaK, groEL, murC, murE, pepX, pyrG, recA, rpoB, and uvrC). MLST analysis of 203 isolates of L. fermentum from Mongolia and seven provinces/ autonomous regions in China identified 57 sequence types (ST), 27 of which were represented by only a single isolate, indicating high genetic diversity. Phylogenetic analyses based on the sequence of the 11 housekeeping gene fragments indicated that the L. fermentum isolates analyzed belonged to two major groups. A standardized index of association (I A (S)) indicated a weak clonal population structure in L. fermentum. Split decomposition analysis indicated that recombination played an important role in generating the genetic diversity observed in L. fermentum. The results from the minimum spanning tree strongly suggested that evolution of L. fermentum STs was not correlated with geography or food-type. The MLST scheme developed will be valuable for further studies on the evolution and population structure of L. fermentum isolates used in food products.

  19. Gas-filled capillaries for plasma-based accelerators

    NASA Astrophysics Data System (ADS)

    Filippi, F.; Anania, M. P.; Brentegani, E.; Biagioni, A.; Cianchi, A.; Chiadroni, E.; Ferrario, M.; Pompili, R.; Romeo, S.; Zigler, A.

    2017-07-01

    Plasma Wakefield Accelerators are based on the excitation of large amplitude plasma waves excited by either a laser or a particle driver beam. The amplitude of the waves, as well as their spatial dimensions and the consequent accelerating gradient depend strongly on the background electron density along the path of the accelerated particles. The process needs stable and reliable plasma sources, whose density profile must be controlled and properly engineered to ensure the appropriate accelerating mechanism. Plasma confinement inside gas filled capillaries have been studied in the past since this technique allows to control the evolution of the plasma, ensuring a stable and repeatable plasma density distribution during the interaction with the drivers. Moreover, in a gas filled capillary plasma can be pre-ionized by a current discharge to avoid ionization losses. Different capillary geometries have been studied to allow the proper temporal and spatial evolution of the plasma along the acceleration length. Results of this analysis obtained by varying the length and the number of gas inlets will be presented.

  20. Nearly complete 28S rRNA gene sequences confirm new hypotheses of sponge evolution.

    PubMed

    Thacker, Robert W; Hill, April L; Hill, Malcolm S; Redmond, Niamh E; Collins, Allen G; Morrow, Christine C; Spicer, Lori; Carmack, Cheryl A; Zappe, Megan E; Pohlmann, Deborah; Hall, Chelsea; Diaz, Maria C; Bangalore, Purushotham V

    2013-09-01

    The highly collaborative research sponsored by the NSF-funded Assembling the Porifera Tree of Life (PorToL) project is providing insights into some of the most difficult questions in metazoan systematics. Our understanding of phylogenetic relationships within the phylum Porifera has changed considerably with increased taxon sampling and data from additional molecular markers. PorToL researchers have falsified earlier phylogenetic hypotheses, discovered novel phylogenetic alliances, found phylogenetic homes for enigmatic taxa, and provided a more precise understanding of the evolution of skeletal features, secondary metabolites, body organization, and symbioses. Some of these exciting new discoveries are shared in the papers that form this issue of Integrative and Comparative Biology. Our analyses of over 300 nearly complete 28S ribosomal subunit gene sequences provide specific case studies that illustrate how our dataset confirms new hypotheses of sponge evolution. We recovered monophyletic clades for all 4 classes of sponges, as well as the 4 major clades of Demospongiae (Keratosa, Myxospongiae, Haploscleromorpha, and Heteroscleromorpha), but our phylogeny differs in several aspects from traditional classifications. In most major clades of sponges, families within orders appear to be paraphyletic. Although additional sampling of genes and taxa are needed to establish whether this pattern results from a lack of phylogenetic resolution or from a paraphyletic classification system, many of our results are congruent with those obtained from 18S ribosomal subunit gene sequences and complete mitochondrial genomes. These data provide further support for a revision of the traditional classification of sponges.

  1. Evolution of branched regulatory genetic pathways: directional selection on pleiotropic loci accelerates developmental system drift.

    PubMed

    Johnson, Norman A; Porter, Adam H

    2007-01-01

    Developmental systems are regulated by a web of interacting loci. One common and useful approach in studying the evolution of development is to focus on classes of interacting elements within these systems. Here, we use individual-based simulations to study the evolution of traits controlled by branched developmental pathways involving three loci, where one locus regulates two different traits. We examined the system under a variety of selective regimes. In the case where one branch was under stabilizing selection and the other under directional selection, we observed "developmental system drift": the trait under stabilizing selection showed little phenotypic change even though the loci underlying that trait showed considerable evolutionary divergence. This occurs because the pleiotropic locus responds to directional selection and compensatory mutants are then favored in the pathway under stabilizing selection. Though developmental system drift may be caused by other mechanisms, it seems likely that it is accelerated by the same underlying genetic mechanism as that producing the Dobzhansky-Muller incompatibilities that lead to speciation in both linear and branched pathways. We also discuss predictions of our model for developmental system drift and how different selective regimes affect probabilities of speciation in the branched pathway system.

  2. The C Terminus of Formin FMNL3 Accelerates Actin Polymerization and Contains a WH2 Domain-like Sequence That Binds Both Monomers and Filament Barbed Ends*

    PubMed Central

    Heimsath, Ernest G.; Higgs, Henry N.

    2012-01-01

    Formin proteins are actin assembly factors that accelerate filament nucleation then remain on the elongating barbed end and modulate filament elongation. The formin homology 2 (FH2) domain is central to these activities, but recent work has suggested that additional sequences enhance FH2 domain function. Here we show that the C-terminal 76 amino acids of the formin FMNL3 have a dramatic effect on the ability of the FH2 domain to accelerate actin assembly. This C-terminal region contains a WASp homology 2 (WH2)-like sequence that binds actin monomers in a manner that is competitive with other WH2 domains and with profilin. In addition, the C terminus binds filament barbed ends. As a monomer, the FMNL3 C terminus inhibits actin polymerization and slows barbed end elongation with moderate affinity. As a dimer, the C terminus accelerates actin polymerization from monomers and displays high affinity inhibition of barbed end elongation. These properties are not common to all formin C termini, as those of mDia1 and INF2 do not behave similarly. Interestingly, mutation of two aliphatic residues, which blocks high affinity actin binding by the WH2-like sequence, has no effect on the ability of the C terminus to enhance FH2-mediated polymerization. However, mutation of three successive basic residues at the C terminus of the WH2-like sequence compromises polymerization enhancement. These results illustrate that the C termini of formins are highly diverse in their interactions with actin. PMID:22094460

  3. Stratigraphic framework and evolution of the Cretaceous continental sequences of the Bauru, Sanfranciscana, and Parecis basins, Brazil

    NASA Astrophysics Data System (ADS)

    Batezelli, Alessandro; Ladeira, Francisco Sergio Bernardes

    2016-01-01

    With the breakup of the supercontinent Gondwana, the South American Plate has undergone an intense process of tectonic restructuring that led to the genesis of the interior basins that encompassed continental sedimentary sequences. The Brazilian Bauru, Sanfranciscana and Parecis basins during Late Cretaceous have had their evolution linked to this process of structuring and therefore have very similar sedimentary characteristics. The purpose of this study is to establish a detailed understanding of alluvial sedimentary processes and architecture within a stratigraphic sequence framework using the concept of the stratigraphic base level or the ratio between the accommodation space and sediment supply. The integration of the stratigraphic and facies data contributed to defining the stratigraphic architecture of the Bauru, Sanfranciscana and Parecis Basins, supporting a model for continental sequences that depicts qualitative changes in the sedimentation rate (S) and accommodation space (A) that occurred during the Cretaceous. This study discusses the origin of the unconformity surfaces (K-0, K-1 and K-1A) that separate Sequences 1, 2A and 2B and the sedimentary characteristics of the Bauru, Sanfranciscana and Parecis Basins from the Aptian to the Maastrichtian, comparing the results with other Cretaceous Brazilian basins. The lower Cretaceous Sequence 1 (Caiuá and Areado groups) is interpreted as a low-accommodation systems tract compound by fluvial and aeolian systems. The upper Cretaceous lacustrine, braided river-dominated alluvial fan and aeolian systems display characteristics of the evolution from high-to low-accommodation systems tracts (Sequences 2A and 2B). Unconformity K-0 is related to the origin of the Bauru Basin itself in the Early Cretaceous. In Sanfranciscana and Parecis basins, the unconformity K-0 marks the contact between aeolian deposits from Lower Cretaceous and Upper Cretaceous alluvial systems (Sequences 1 and 2). Unconformity K-1, which was

  4. Evolution of gilled mushrooms and puffballs inferred from ribosomal DNA sequences

    PubMed Central

    Hibbett, David S.; Pine, Elizabeth M.; Langer, Ewald; Langer, Gitta; Donoghue, Michael J.

    1997-01-01

    Homobasidiomycete fungi display many complex fruiting body morphologies, including mushrooms and puffballs, but their anatomical simplicity has confounded efforts to understand the evolution of these forms. We performed a comprehensive phylogenetic analysis of homobasidiomycetes, using sequences from nuclear and mitochondrial ribosomal DNA, with an emphasis on understanding evolutionary relationships of gilled mushrooms and puffballs. Parsimony-based optimization of character states on our phylogenetic trees suggested that strikingly similar gilled mushrooms evolved at least six times, from morphologically diverse precursors. Approximately 87% of gilled mushrooms are in a single lineage, which we call the “euagarics.” Recently discovered 90 million-year-old fossil mushrooms are probably euagarics, suggesting that (i) the origin of this clade must have occurred no later than the mid-Cretaceous and (ii) the gilled mushroom morphology has been maintained in certain lineages for tens of millions of years. Puffballs and other forms with enclosed spore-bearing structures (Gasteromycetes) evolved at least four times. Derivation of Gasteromycetes from forms with exposed spore-bearing structures (Hymenomycetes) is correlated with repeated loss of forcible spore discharge (ballistospory). Diverse fruiting body forms and spore dispersal mechanisms have evolved among Gasteromycetes. Nevertheless, it appears that Hymenomycetes have never been secondarily derived from Gasteromycetes, which suggests that the loss of ballistospory has constrained evolution in these lineages. PMID:9342352

  5. Pipeline for large-scale microdroplet bisulfite PCR-based sequencing allows the tracking of hepitype evolution in tumors.

    PubMed

    Herrmann, Alexander; Haake, Andrea; Ammerpohl, Ole; Martin-Guerrero, Idoia; Szafranski, Karol; Stemshorn, Kathryn; Nothnagel, Michael; Kotsopoulos, Steve K; Richter, Julia; Warner, Jason; Olson, Jeff; Link, Darren R; Schreiber, Stefan; Krawczak, Michael; Platzer, Matthias; Nürnberg, Peter; Siebert, Reiner; Hampe, Jochen

    2011-01-01

    Cytosine methylation provides an epigenetic level of cellular plasticity that is important for development, differentiation and cancerogenesis. We adopted microdroplet PCR to bisulfite treated target DNA in combination with second generation sequencing to simultaneously assess DNA sequence and methylation. We show measurement of methylation status in a wide range of target sequences (total 34 kb) with an average coverage of 95% (median 100%) and good correlation to the opposite strand (rho = 0.96) and to pyrosequencing (rho = 0.87). Data from lymphoma and colorectal cancer samples for SNRPN (imprinted gene), FGF6 (demethylated in the cancer samples) and HS3ST2 (methylated in the cancer samples) serve as a proof of principle showing the integration of SNP data and phased DNA-methylation information into "hepitypes" and thus the analysis of DNA methylation phylogeny in the somatic evolution of cancer.

  6. Complete cDNA sequence of SAP-like pentraxin from Limulus polyphemus: implications for pentraxin evolution.

    PubMed

    Tharia, Hazel A; Shrive, Annette K; Mills, John D; Arme, Chris; Williams, Gwyn T; Greenhough, Trevor J

    2002-02-22

    The serum amyloid P component (SAP)-like pentraxin Limulus polyphemus SAP is a recently discovered, distinct pentraxin species, of known structure, which does not bind phosphocholine and whose N-terminal sequence has been shown to differ markedly from the highly conserved N terminus of all other known horseshoe crab pentraxins. The complete cDNA sequence of Limulus SAP, and the derived amino acid sequence, the first invertebrate SAP-like pentraxin sequence, have been determined. Two sequences were identified that differed only in the length of the 3' untranslated region. Limulus SAP is synthesised as a precursor protein of 234 amino acid residues, the first 17 residues encoding a signal peptide that is absent from the mature protein. Phylogenetic analysis clusters Limulus SAP pentraxin with the horseshoe crab C-reactive proteins (CRPs) rather than the mammalian SAPs, which are clustered with mammalian CRPs. The deduced amino acid sequence shares 22% identity with both human SAP and CRP, which are 51% identical, and 31-35% with horseshoe crab CRPs. These analyses indicate that gene duplication of CRP (or SAP), followed by sequence divergence and the evolution of CRP and/or SAP function, occurred independently along the chordate and arthropod evolutionary lines rather than in a common ancestor. They further indicate that the CRP/SAP gene duplication event in Limulus occurred before both the emergence of the Limulus CRP variants and the mammalian CRP/SAP gene duplication. Limulus SAP, which does not exhibit the CRP characteristic of calcium-dependent binding to phosphocholine, is established as a pentraxin species distinct from all other known horseshoe crab pentraxins that exist in many variant forms sharing a high level of sequence homology. Copyright 2002 Elsevier Science Ltd.

  7. Accelerating next generation sequencing data analysis with system level optimizations.

    PubMed

    Kathiresan, Nagarajan; Temanni, Ramzi; Almabrazi, Hakeem; Syed, Najeeb; Jithesh, Puthen V; Al-Ali, Rashid

    2017-08-22

    Next generation sequencing (NGS) data analysis is highly compute intensive. In-memory computing, vectorization, bulk data transfer, CPU frequency scaling are some of the hardware features in the modern computing architectures. To get the best execution time and utilize these hardware features, it is necessary to tune the system level parameters before running the application. We studied the GATK-HaplotypeCaller which is part of common NGS workflows, that consume more than 43% of the total execution time. Multiple GATK 3.x versions were benchmarked and the execution time of HaplotypeCaller was optimized by various system level parameters which included: (i) tuning the parallel garbage collection and kernel shared memory to simulate in-memory computing, (ii) architecture-specific tuning in the PairHMM library for vectorization, (iii) including Java 1.8 features through GATK source code compilation and building a runtime environment for parallel sorting and bulk data transfer (iv) the default 'on-demand' mode of CPU frequency is over-clocked by using 'performance-mode' to accelerate the Java multi-threads. As a result, the HaplotypeCaller execution time was reduced by 82.66% in GATK 3.3 and 42.61% in GATK 3.7. Overall, the execution time of NGS pipeline was reduced to 70.60% and 34.14% for GATK 3.3 and GATK 3.7 respectively.

  8. Draft genome sequence of pigeonpea (Cajanus cajan), an orphan legume crop of resource-poor farmers.

    PubMed

    Varshney, Rajeev K; Chen, Wenbin; Li, Yupeng; Bharti, Arvind K; Saxena, Rachit K; Schlueter, Jessica A; Donoghue, Mark T A; Azam, Sarwar; Fan, Guangyi; Whaley, Adam M; Farmer, Andrew D; Sheridan, Jaime; Iwata, Aiko; Tuteja, Reetu; Penmetsa, R Varma; Wu, Wei; Upadhyaya, Hari D; Yang, Shiaw-Pyng; Shah, Trushar; Saxena, K B; Michael, Todd; McCombie, W Richard; Yang, Bicheng; Zhang, Gengyun; Yang, Huanming; Wang, Jun; Spillane, Charles; Cook, Douglas R; May, Gregory D; Xu, Xun; Jackson, Scott A

    2011-11-06

    Pigeonpea is an important legume food crop grown primarily by smallholder farmers in many semi-arid tropical regions of the world. We used the Illumina next-generation sequencing platform to generate 237.2 Gb of sequence, which along with Sanger-based bacterial artificial chromosome end sequences and a genetic map, we assembled into scaffolds representing 72.7% (605.78 Mb) of the 833.07 Mb pigeonpea genome. Genome analysis predicted 48,680 genes for pigeonpea and also showed the potential role that certain gene families, for example, drought tolerance-related genes, have played throughout the domestication of pigeonpea and the evolution of its ancestors. Although we found a few segmental duplication events, we did not observe the recent genome-wide duplication events observed in soybean. This reference genome sequence will facilitate the identification of the genetic basis of agronomically important traits, and accelerate the development of improved pigeonpea varieties that could improve food security in many developing countries.

  9. The Evolution of the Observed Hubble Sequence over the past 6Gyr

    NASA Astrophysics Data System (ADS)

    Delgado-Serrano, R.; Hammer, F.; Yang, Y. B.; Puech, M.; Flores, H.; Rodrigues, M.

    2011-10-01

    During the past years we have confronted serious problems of methodology concerning the morphological and kinematic classification of distant galaxies. This has forced us to create a new simple and effective morphological classification methodology, in order to guarantee a morpho-kinematic correlation, make the reproducibility easier and restrict the classification subjectivity. Giving the characteristic of our morphological classification, we have thus been able to apply the same methodology, using equivalent observations, to representative samples of local and distant galaxies. It has allowed us to derive, for the first time, the distant Hubble sequence (~6 Gyr ago), and determine a morphological evolution of galaxies over the past 6 Gyr. Our results strongly suggest that more than half of the present-day spirals had peculiar morphologies, 6 Gyr ago.

  10. Rational evolutionary design: the theory of in vitro protein evolution.

    PubMed

    Voigt, C A; Kauffman, S; Wang, Z G

    2000-01-01

    related to the number of uphill paths, which decreases more rapidly for rugged landscapes. Noise in the fitness measurements causes a dramatic increase in the required mutant library size, thus implying a smaller optimal mutation rate. Because of strict limitations on the number of mutants that can be screened, there is motivation to optimize the content of the mutant library. By restricting mutations to regions of the gene that are expected to show improvement, a greater return can be made with the same number of mutants. Initial studies with subtilisin E have shown that structurally tolerant positions tend to be where positive activity mutants are made during directed evolution. Mutant fitness information is produced by the screening step that has the potential to provide insight into the structure of the fitness landscape, thus aiding the setting of experimental parameters. By analyzing the mutant fitness distribution and targeting specific regions of the sequence, in vitro evolution can be accelerated. However, when expediting the search, there is a trade-off between rapid improvement and the quality of the long-term solution. The benefit of neutrality has yet to be captured with in vitro protein evolution. Neutral theory predicts the punctuated emergence of novel structure and function, however, with current methods, the required time scale is not feasible. Utilizing neutral evolution to accelerate the discovery of new functional and structural solutions requires a theory that predicts the behavior of mutational pathways between networks. Because the transition from neutral to adaptive evolution requires a multi-mutational switch, increasing the mutation rate decreases the time required for a punctuated change to occur. By limiting the search to the less coupled region of the sequence (smooth portion of the fitness landscape), the required larger mutation rate can be tolerated. Advances in directed evolution will be achieved when the driving forces behind such proce

  11. Peregrine and saker falcon genome sequences provide insights into evolution of a predatory lifestyle.

    PubMed

    Zhan, Xiangjiang; Pan, Shengkai; Wang, Junyi; Dixon, Andrew; He, Jing; Muller, Margit G; Ni, Peixiang; Hu, Li; Liu, Yuan; Hou, Haolong; Chen, Yuanping; Xia, Jinquan; Luo, Qiong; Xu, Pengwei; Chen, Ying; Liao, Shengguang; Cao, Changchang; Gao, Shukun; Wang, Zhaobao; Yue, Zhen; Li, Guoqing; Yin, Ye; Fox, Nick C; Wang, Jun; Bruford, Michael W

    2013-05-01

    As top predators, falcons possess unique morphological, physiological and behavioral adaptations that allow them to be successful hunters: for example, the peregrine is renowned as the world's fastest animal. To examine the evolutionary basis of predatory adaptations, we sequenced the genomes of both the peregrine (Falco peregrinus) and saker falcon (Falco cherrug), and we present parallel, genome-wide evidence for evolutionary innovation and selection for a predatory lifestyle. The genomes, assembled using Illumina deep sequencing with greater than 100-fold coverage, are both approximately 1.2 Gb in length, with transcriptome-assisted prediction of approximately 16,200 genes for both species. Analysis of 8,424 orthologs in both falcons, chicken, zebra finch and turkey identified consistent evidence for genome-wide rapid evolution in these raptors. SNP-based inference showed contrasting recent demographic trajectories for the two falcons, and gene-based analysis highlighted falcon-specific evolutionary novelties for beak development and olfaction and specifically for homeostasis-related genes in the arid environment-adapted saker.

  12. The modern temperature-accelerated dynamics approach

    DOE PAGES

    Zamora, Richard J.; Uberuaga, Blas P.; Perez, Danny; ...

    2016-06-01

    Accelerated molecular dynamics (AMD) is a class of MD-based methods used to simulate atomistic systems in which the metastable state-to-state evolution is slow compared with thermal vibrations. Temperature-accelerated dynamics (TAD) is a particularly efficient AMD procedure in which the predicted evolution is hastened by elevating the temperature of the system and then recovering the correct state-to-state dynamics at the temperature of interest. TAD has been used to study various materials applications, often revealing surprising behavior beyond the reach of direct MD. This success has inspired several algorithmic performance enhancements, as well as the analysis of its mathematical framework. Recently, thesemore » enhancements have leveraged parallel programming techniques to enhance both the spatial and temporal scaling of the traditional approach. Here, we review the ongoing evolution of the modern TAD method and introduce the latest development: speculatively parallel TAD.« less

  13. A comprehensive draft genome sequence for lupin (Lupinus angustifolius), an emerging health food: insights into plant-microbe interactions and legume evolution.

    PubMed

    Hane, James K; Ming, Yao; Kamphuis, Lars G; Nelson, Matthew N; Garg, Gagan; Atkins, Craig A; Bayer, Philipp E; Bravo, Armando; Bringans, Scott; Cannon, Steven; Edwards, David; Foley, Rhonda; Gao, Ling-Ling; Harrison, Maria J; Huang, Wei; Hurgobin, Bhavna; Li, Sean; Liu, Cheng-Wu; McGrath, Annette; Morahan, Grant; Murray, Jeremy; Weller, James; Jian, Jianbo; Singh, Karam B

    2017-03-01

    Lupins are important grain legume crops that form a critical part of sustainable farming systems, reducing fertilizer use and providing disease breaks. It has a basal phylogenetic position relative to other crop and model legumes and a high speciation rate. Narrow-leafed lupin (NLL; Lupinus angustifolius L.) is gaining popularity as a health food, which is high in protein and dietary fibre but low in starch and gluten-free. We report the draft genome assembly (609 Mb) of NLL cultivar Tanjil, which has captured >98% of the gene content, sequences of additional lines and a dense genetic map. Lupins are unique among legumes and differ from most other land plants in that they do not form mycorrhizal associations. Remarkably, we find that NLL has lost all mycorrhiza-specific genes, but has retained genes commonly required for mycorrhization and nodulation. In addition, the genome also provided candidate genes for key disease resistance and domestication traits. We also find evidence of a whole-genome triplication at around 25 million years ago in the genistoid lineage leading to Lupinus. Our results will support detailed studies of legume evolution and accelerate lupin breeding programmes. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  14. Nearly Complete 28S rRNA Gene Sequences Confirm New Hypotheses of Sponge Evolution

    PubMed Central

    Thacker, Robert W.; Hill, April L.; Hill, Malcolm S.; Redmond, Niamh E.; Collins, Allen G.; Morrow, Christine C.; Spicer, Lori; Carmack, Cheryl A.; Zappe, Megan E.; Pohlmann, Deborah; Hall, Chelsea; Diaz, Maria C.; Bangalore, Purushotham V.

    2013-01-01

    The highly collaborative research sponsored by the NSF-funded Assembling the Porifera Tree of Life (PorToL) project is providing insights into some of the most difficult questions in metazoan systematics. Our understanding of phylogenetic relationships within the phylum Porifera has changed considerably with increased taxon sampling and data from additional molecular markers. PorToL researchers have falsified earlier phylogenetic hypotheses, discovered novel phylogenetic alliances, found phylogenetic homes for enigmatic taxa, and provided a more precise understanding of the evolution of skeletal features, secondary metabolites, body organization, and symbioses. Some of these exciting new discoveries are shared in the papers that form this issue of Integrative and Comparative Biology. Our analyses of over 300 nearly complete 28S ribosomal subunit gene sequences provide specific case studies that illustrate how our dataset confirms new hypotheses of sponge evolution. We recovered monophyletic clades for all 4 classes of sponges, as well as the 4 major clades of Demospongiae (Keratosa, Myxospongiae, Haploscleromorpha, and Heteroscleromorpha), but our phylogeny differs in several aspects from traditional classifications. In most major clades of sponges, families within orders appear to be paraphyletic. Although additional sampling of genes and taxa are needed to establish whether this pattern results from a lack of phylogenetic resolution or from a paraphyletic classification system, many of our results are congruent with those obtained from 18S ribosomal subunit gene sequences and complete mitochondrial genomes. These data provide further support for a revision of the traditional classification of sponges. PMID:23748742

  15. Combining protein sequence, structure, and dynamics: A novel approach for functional evolution analysis of PAS domain superfamily.

    PubMed

    Dong, Zheng; Zhou, Hongyu; Tao, Peng

    2018-02-01

    PAS domains are widespread in archaea, bacteria, and eukaryota, and play important roles in various functions. In this study, we aim to explore functional evolutionary relationship among proteins in the PAS domain superfamily in view of the sequence-structure-dynamics-function relationship. We collected protein sequences and crystal structure data from RCSB Protein Data Bank of the PAS domain superfamily belonging to three biological functions (nucleotide binding, photoreceptor activity, and transferase activity). Protein sequences were aligned and then used to select sequence-conserved residues and build phylogenetic tree. Three-dimensional structure alignment was also applied to obtain structure-conserved residues. The protein dynamics were analyzed using elastic network model (ENM) and validated by molecular dynamics (MD) simulation. The result showed that the proteins with same function could be grouped by sequence similarity, and proteins in different functional groups displayed statistically significant difference in their vibrational patterns. Interestingly, in all three functional groups, conserved amino acid residues identified by sequence and structure conservation analysis generally have a lower fluctuation than other residues. In addition, the fluctuation of conserved residues in each biological function group was strongly correlated with the corresponding biological function. This research suggested a direct connection in which the protein sequences were related to various functions through structural dynamics. This is a new attempt to delineate functional evolution of proteins using the integrated information of sequence, structure, and dynamics. © 2017 The Protein Society.

  16. Superconducting Magnets for Particle Accelerators

    DOE PAGES

    Bottura, Luca; Gourlay, Stephen A.; Yamamoto, Akira; ...

    2015-11-10

    In this study, we summarize the evolution and contributions of superconducting magnets to particle accelerators as chronicled over the last 50 years of Particle Accelerator Conferences (PAC, NA-PAC and IPAC). We begin with an historical overview based primarily on PAC Proceedings augmented with references to key milestones in the development of superconducting magnets for particle accelerators. We then provide some illustrative examples of applications that have occurred over the past 50 years, focusing on those that have either been realized in practice or provided technical development for other projects, with discussion of possible future applications.

  17. Superconducting Magnets for Particle Accelerators

    NASA Astrophysics Data System (ADS)

    Bottura, Luca; Gourlay, Stephen A.; Yamamoto, Akira; Zlobin, Alexander V.

    2016-04-01

    In this paper we summarize the evolution and contributions of superconducting magnets to particle accelerators as chronicled over the last 50 years of Particle Accelerator Conferences (PAC, NA-PAC and IPAC). We begin with an historical overview based primarily on PAC Proceedings augmented with references to key milestones in the development of superconducting magnets for particle accelerators. We then provide some illustrative examples of applications that have occurred over the past 50 years, focusing on those that have either been realized in practice or provided technical development for other projects, with discussion of possible future applications.

  18. Centromere and telomere sequence alterations reflect the rapid genome evolution within the carnivorous plant genus Genlisea.

    PubMed

    Tran, Trung D; Cao, Hieu X; Jovtchev, Gabriele; Neumann, Pavel; Novák, Petr; Fojtová, Miloslava; Vu, Giang T H; Macas, Jiří; Fajkus, Jiří; Schubert, Ingo; Fuchs, Joerg

    2015-12-01

    Linear chromosomes of eukaryotic organisms invariably possess centromeres and telomeres to ensure proper chromosome segregation during nuclear divisions and to protect the chromosome ends from deterioration and fusion, respectively. While centromeric sequences may differ between species, with arrays of tandemly repeated sequences and retrotransposons being the most abundant sequence types in plant centromeres, telomeric sequences are usually highly conserved among plants and other organisms. The genome size of the carnivorous genus Genlisea (Lentibulariaceae) is highly variable. Here we study evolutionary sequence plasticity of these chromosomal domains at an intrageneric level. We show that Genlisea nigrocaulis (1C = 86 Mbp; 2n = 40) and G. hispidula (1C = 1550 Mbp; 2n = 40) differ as to their DNA composition at centromeres and telomeres. G. nigrocaulis and its close relative G. pygmaea revealed mainly 161 bp tandem repeats, while G. hispidula and its close relative G. subglabra displayed a combination of four retroelements at centromeric positions. G. nigrocaulis and G. pygmaea chromosome ends are characterized by the Arabidopsis-type telomeric repeats (TTTAGGG); G. hispidula and G. subglabra instead revealed two intermingled sequence variants (TTCAGG and TTTCAGG). These differences in centromeric and, surprisingly, also in telomeric DNA sequences, uncovered between groups with on average a > 9-fold genome size difference, emphasize the fast genome evolution within this genus. Such intrageneric evolutionary alteration of telomeric repeats with cytosine in the guanine-rich strand, not yet known for plants, might impact the epigenetic telomere chromatin modification. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  19. Evolution of the human-specific microRNA miR-941

    PubMed Central

    Hu, Hai Yang; He, Liu; Fominykh, Kseniya; Yan, Zheng; Guo, Song; Zhang, Xiaoyu; Taylor, Martin S.; Tang, Lin; Li, Jie; Liu, Jianmei; Wang, Wen; Yu, Haijing; Khaitovich, Philipp

    2012-01-01

    MicroRNA-mediated gene regulation is important in many physiological processes. Here we explore the roles of a microRNA, miR-941, in human evolution. We find that miR-941 emerged de novo in the human lineage, between six and one million years ago, from an evolutionarily volatile tandem repeat sequence. Its copy-number remains polymorphic in humans and shows a trend for decreasing copy-number with migration out of Africa. Emergence of miR-941 was accompanied by accelerated loss of miR-941-binding sites, presumably to escape regulation. We further show that miR-941 is highly expressed in pluripotent cells, repressed upon differentiation and preferentially targets genes in hedgehog- and insulin-signalling pathways, thus suggesting roles in cellular differentiation. Human-specific effects of miR-941 regulation are detectable in the brain and affect genes involved in neurotransmitter signalling. Taken together, these results implicate miR-941 in human evolution, and provide an example of rapid regulatory evolution in the human linage. PMID:23093182

  20. The evolution of surface magnetic fields in young solar-type stars II: the early main sequence (250-650 Myr)

    NASA Astrophysics Data System (ADS)

    Folsom, C. P.; Bouvier, J.; Petit, P.; Lèbre, A.; Amard, L.; Palacios, A.; Morin, J.; Donati, J.-F.; Vidotto, A. A.

    2018-03-01

    There is a large change in surface rotation rates of sun-like stars on the pre-main sequence and early main sequence. Since these stars have dynamo-driven magnetic fields, this implies a strong evolution of their magnetic properties over this time period. The spin-down of these stars is controlled by interactions between stellar and magnetic fields, thus magnetic evolution in turn plays an important role in rotational evolution. We present here the second part of a study investigating the evolution of large-scale surface magnetic fields in this critical time period. We observed stars in open clusters and stellar associations with known ages between 120 and 650 Myr, and used spectropolarimetry and Zeeman Doppler Imaging to characterize their large-scale magnetic field strength and geometry. We report 15 stars with magnetic detections here. These stars have masses from 0.8 to 0.95 M⊙, rotation periods from 0.326 to 10.6 d, and we find large-scale magnetic field strengths from 8.5 to 195 G with a wide range of geometries. We find a clear trend towards decreasing magnetic field strength with age, and a power law decrease in magnetic field strength with Rossby number. There is some tentative evidence for saturation of the large-scale magnetic field strength at Rossby numbers below 0.1, although the saturation point is not yet well defined. Comparing to younger classical T Tauri stars, we support the hypothesis that differences in internal structure produce large differences in observed magnetic fields, however for weak-lined T Tauri stars this is less clear.

  1. Accelerated probabilistic inference of RNA structure evolution

    PubMed Central

    Holmes, Ian

    2005-01-01

    Background Pairwise stochastic context-free grammars (Pair SCFGs) are powerful tools for evolutionary analysis of RNA, including simultaneous RNA sequence alignment and secondary structure prediction, but the associated algorithms are intensive in both CPU and memory usage. The same problem is faced by other RNA alignment-and-folding algorithms based on Sankoff's 1985 algorithm. It is therefore desirable to constrain such algorithms, by pre-processing the sequences and using this first pass to limit the range of structures and/or alignments that can be considered. Results We demonstrate how flexible classes of constraint can be imposed, greatly reducing the computational costs while maintaining a high quality of structural homology prediction. Any score-attributed context-free grammar (e.g. energy-based scoring schemes, or conditionally normalized Pair SCFGs) is amenable to this treatment. It is now possible to combine independent structural and alignment constraints of unprecedented general flexibility in Pair SCFG alignment algorithms. We outline several applications to the bioinformatics of RNA sequence and structure, including Waterman-Eggert N-best alignments and progressive multiple alignment. We evaluate the performance of the algorithm on test examples from the RFAM database. Conclusion A program, Stemloc, that implements these algorithms for efficient RNA sequence alignment and structure prediction is available under the GNU General Public License. PMID:15790387

  2. Accelerated evolution of the Lyα luminosity function at z ≳ 7 revealed by the Subaru ultra-deep survey for Lyα emitters at z = 7.3

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Konno, Akira; Ouchi, Masami; Ono, Yoshiaki

    2014-12-10

    We present the ultra-deep Subaru narrowband imaging survey for Lyα emitters (LAEs) at z = 7.3 in the Subaru/XMM-Newton Deep Survey (SXDS) and Cosmic Evolution Survey (COSMOS) fields (∼0.5 deg{sup 2}) with a total integration time of 106 hr. Exploiting our new sharp bandwidth filter, NB101, installed on the Suprime-Cam, we have reached L(Lyα) = 2.4 × 10{sup 42} erg s{sup –1} (5σ) for z = 7.3 LAEs, about four times deeper than previous Subaru z ≳ 7 studies, which allows us to reliably investigate the evolution of the Lyα luminosity function (LF) for the first time down to themore » luminosity limit same as those of Subaru z = 3.1-6.6 LAE samples. Surprisingly, we only find three and four LAEs in the SXDS and COSMOS fields, respectively, while one expects a total of ∼65 LAEs by our survey in the case of no Lyα LF evolution from z = 6.6 to 7.3. We identify a decrease of the Lyα LF from z = 6.6 to 7.3 at the >90% confidence level from our z = 7.3 Lyα LF with the best-fit Schechter parameters of L{sub Lyα}{sup ∗}=2.7{sub −1.2}{sup +8.0}×10{sup 42} erg s{sup −1} and ϕ{sup ∗}=3.7{sub −3.3}{sup +17.6}×10{sup −4} Mpc{sup −3} for a fixed α = –1.5. Moreover, the evolution of the Lyα LF is clearly accelerated at z > 6.6 beyond the measurement uncertainties including cosmic variance. Because no such accelerated evolution of the UV-continuum LF or the cosmic star formation rate (SFR) is found at z ∼ 7, but suggested only at z > 8, this accelerated Lyα LF evolution is explained by physical mechanisms different from a pure SFR decrease but related to the Lyα production and escape in the process of cosmic reionization. Because a simple accelerating increase of intergalactic medium neutral hydrogen absorbing Lyα cannot be reconciled with Thomson scattering of optical depth measurements from WMAP and Planck, our findings may support new physical pictures suggested by recent theoretical studies, such as the existence of HI clumpy clouds

  3. Late Pleistocene acceleration of deformation across the northern Tianshan piedmont (China) evidenced from the morpho-tectonic evolution of the Dushanzi anticline

    NASA Astrophysics Data System (ADS)

    Charreau, Julien; Saint-Carlier, Dimitri; Lavé, Jérôme; Dominguez, Stéphane; Blard, Pierre-Henri; Avouac, Jean-Philippe; Brown, Nathan D.; Malatesta, Luca Claude; Wang, Shengli; Rhodes, Edward J.

    2018-04-01

    We document the temporal evolution of deformation in the northern Tianshan piedmont where the deformation is partitioned across several thrusts and folds. We focus on the Dushanzi anticline, where abandoned terraces and growth strata allow us to constrain the history of folding since the Miocene. Based on subsurface seismic imaging, structural measurements and morphological analysis, we show that this anticline is associated with two decollement levels. We use kink band migration in growth strata dated by paleomagnetism to constrain the shortening from the Mio-Pliocene to the Holocene. Our results show that the Dushanzi anticline has been active since at least 8 Ma and that the fold grew at a steady shortening rate of 0.6 ± 0.1 mm/yr from 8 to 1.5 Ma with possible variations from 2.5 to 1.5 Ma. Then it accelerated rapidly to a rate of 4.3 ± 1.0 mm/yr over at least the last 100 ka. These results, together with similar temporal shortening evolutions across other structures, suggest that the deformation rate across the eastern Tianshan piedmont increased relatively recently. This may reflect either a redistribution of the deformation from the internal structures toward the borders or a general acceleration of the deformation across the entire range.

  4. Adaptability and evolution.

    PubMed

    Bateson, Patrick

    2017-10-06

    The capacity of organisms to respond in their own lifetimes to new challenges in their environments probably appeared early in biological evolution. At present few studies have shown how such adaptability could influence the inherited characteristics of an organism's descendants. In part, this has been because organisms have been treated as passive in evolution. Nevertheless, their effects on biological evolution are likely to have been important and, when they occurred, accelerated the pace of evolution. Ways in which this might have happened have been suggested many times since the 1870s. I review these proposals and discuss their relevance to modern thought.

  5. SW#db: GPU-Accelerated Exact Sequence Similarity Database Search.

    PubMed

    Korpar, Matija; Šošić, Martin; Blažeka, Dino; Šikić, Mile

    2015-01-01

    In recent years we have witnessed a growth in sequencing yield, the number of samples sequenced, and as a result-the growth of publicly maintained sequence databases. The increase of data present all around has put high requirements on protein similarity search algorithms with two ever-opposite goals: how to keep the running times acceptable while maintaining a high-enough level of sensitivity. The most time consuming step of similarity search are the local alignments between query and database sequences. This step is usually performed using exact local alignment algorithms such as Smith-Waterman. Due to its quadratic time complexity, alignments of a query to the whole database are usually too slow. Therefore, the majority of the protein similarity search methods prior to doing the exact local alignment apply heuristics to reduce the number of possible candidate sequences in the database. However, there is still a need for the alignment of a query sequence to a reduced database. In this paper we present the SW#db tool and a library for fast exact similarity search. Although its running times, as a standalone tool, are comparable to the running times of BLAST, it is primarily intended to be used for exact local alignment phase in which the database of sequences has already been reduced. It uses both GPU and CPU parallelization and was 4-5 times faster than SSEARCH, 6-25 times faster than CUDASW++ and more than 20 times faster than SSW at the time of writing, using multiple queries on Swiss-prot and Uniref90 databases.

  6. Accelerated rates of protein evolution in barley grain and pistil biased genes might be legacy of domestication.

    PubMed

    Shi, Tao; Dimitrov, Ivan; Zhang, Yinling; Tax, Frans E; Yi, Jing; Gou, Xiaoping; Li, Jia

    2015-10-01

    Traits related to grain and reproductive organs in grass crops have been under continuous directional selection during domestication. Barley is one of the oldest domesticated crops in human history. Thus genes associated with the grain and reproductive organs in barley may show evidence of dramatic evolutionary change. To understand how artificial selection contributes to protein evolution of biased genes in different barley organs, we used Digital Gene Expression analysis of six barley organs (grain, pistil, anther, leaf, stem and root) to identify genes with biased expression in specific organs. Pairwise comparisons of orthologs between barley and Brachypodium distachyon, as well as between highland and lowland barley cultivars mutually indicated that grain and pistil biased genes show relatively higher protein evolutionary rates compared with the median of all orthologs and other organ biased genes. Lineage-specific protein evolutionary rates estimation showed similar patterns with elevated protein evolution in barley grain and pistil biased genes, yet protein sequences generally evolve much faster in the lowland barley cultivar. Further functional annotations revealed that some of these grain and pistil biased genes with rapid protein evolution are related to nutrient biosynthesis and cell cycle/division. Our analyses provide insights into how domestication differentially shaped the evolution of genes specific to different organs of a crop species, and implications for future functional studies of domestication genes.

  7. alpha-Crystallin A sequences of Alligator mississippiensis and the lizard Tupinambis teguixin: molecular evolution and reptilian phylogeny.

    PubMed

    de Jong, W W; Zweers, A; Versteeg, M; Dessauer, H C; Goodman, M

    1985-11-01

    The amino acid sequences of the eye lens protein alpha-crystallin A from many mammalian and avian species, two frog species, and a dogfish have provided detailed information about the molecular evolution of this protein and allowed some useful inferences about phylogenetic relationships among these species. We now have isolated and sequenced the alpha-crystallins of the American alligator and the common tegu lizard. The reptilian alpha A chains appear to have evolved as slowly as those of other vertebrates, i.e., at two to three amino acid replacements per 100 residues in 100 Myr. The lack of charged replacements and the general types and distribution of replacements also are similar to those in other vertebrate alpha A chains. Maximum-parsimony analyses of the total data set of 67 vertebrate alpha A sequences support the monophyletic origin of alligator, tegu, and birds and favor the grouping of crocodilians and birds as surviving sister groups in the subclass Archosauria.

  8. Stochastic modeling of Lagrangian accelerations

    NASA Astrophysics Data System (ADS)

    Reynolds, Andy

    2002-11-01

    It is shown how Sawford's second-order Lagrangian stochastic model (Phys. Fluids A 3, 1577-1586, 1991) for fluid-particle accelerations can be combined with a model for the evolution of the dissipation rate (Pope and Chen, Phys. Fluids A 2, 1437-1449, 1990) to produce a Lagrangian stochastic model that is consistent with both the measured distribution of Lagrangian accelerations (La Porta et al., Nature 409, 1017-1019, 2001) and Kolmogorov's similarity theory. The later condition is found not to be satisfied when a constant dissipation rate is employed and consistency with prescribed acceleration statistics is enforced through fulfilment of a well-mixed condition.

  9. Evolution of glutamine amidotransferase genes. Nucleotide sequences of the pabA genes from Salmonella typhimurium, Klebsiella aerogenes and Serratia marcescens.

    PubMed

    Kaplan, J B; Merkel, W K; Nichols, B P

    1985-06-05

    The amide group of glutamine is a source of nitrogen in the biosynthesis of a variety of compounds. These reactions are catalyzed by a group of enzymes known as glutamine amidotransferases; two of these, the glutamine amidotransferase subunits of p-aminobenzoate synthase and anthranilate synthase have been studied in detail and have been shown to be structurally and functionally related. In some micro-organisms, p-aminobenzoate synthase and anthranilate synthase share a common glutamine amidotransferase subunit. We report here the primary DNA and deduced amino acid sequences of the p-aminobenzoate synthase glutamine amidotransferase subunits from Salmonella typhimurium, Klebsiella aerogenes and Serratia marcescens. A comparison of these glutamine amidotransferase sequences to the sequences of ten others, including some that function specifically in either the p-aminobenzoate synthase or anthranilate synthase complexes and some that are shared by both synthase complexes, has revealed several interesting features of the structure and organization of these genes, and has allowed us to speculate as to the evolutionary history of this family of enzymes. We propose a model for the evolution of the p-aminobenzoate synthase and anthranilate synthase glutamine amidotransferase subunits in which the duplication and subsequent divergence of the genetic information encoding a shared glutamine amidotransferase subunit led to the evolution of two new pathway-specific enzymes.

  10. Late-Time Evolution of Broad-Bandwidth, Laser-Imposed Nonuniformities in Accelerated Foils

    NASA Astrophysics Data System (ADS)

    Smalyuk, V. A.; Boehly, T. R.; Bradley, D. K.; Knauer, J. P.; Meyerhofer, D. D.; Oron, D.; Srebro, Y.; Shvarts, D.

    1998-11-01

    The late-time evolution of broad-bandwidth nonuniformities is studied in planar-foil experiments on the OMEGA laser system. Five beams with ~600-μm-diam uniform region accelerate 20-μm-thick CH foils at an average intensity of 2×10^14\\:W/cm^2 in a 3-ns square pulse. Growth of perturbations seeded by irradiation nonuniformities was observed using time-gated, pinhole photographs of ~1.2-keV x rays from a backlighter. At late times collective saturation is observed at levels similar to Haan's prediction.(S. W. Haan, Phys. Rev. A 39), 5812 (1989). The maximum of the nonuniformity spectrum moves toward longer wavelength in time as expected. Target images taken at different times show the formation of bubbles and spikes from initial elongated ``wormy'' structures. This work was supported by the U.S. Department of Energy Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460, the University of Rochester, and the New York State Energy Research and Development Authority. The support of DOE does not constitute an endorsement by DOE of the views expressed in this article.

  11. Rapid evolution of the env gene leader sequence in cats naturally infected with feline immunodeficiency virus

    PubMed Central

    Hughes, Joseph; Biek, Roman; Litster, Annette; Willett, Brian J.; Hosie, Margaret J.

    2015-01-01

    Analysing the evolution of feline immunodeficiency virus (FIV) at the intra-host level is important in order to address whether the diversity and composition of viral quasispecies affect disease progression. We examined the intra-host diversity and the evolutionary rates of the entire env and structural fragments of the env sequences obtained from sequential blood samples in 43 naturally infected domestic cats that displayed different clinical outcomes. We observed in the majority of cats that FIV env showed very low levels of intra-host diversity. We estimated that env evolved at a rate of 1.16×10−3 substitutions per site per year and demonstrated that recombinant sequences evolved faster than non-recombinant sequences. It was evident that the V3–V5 fragment of FIV env displayed higher evolutionary rates in healthy cats than in those with terminal illness. Our study provided the first evidence that the leader sequence of env, rather than the V3–V5 sequence, had the highest intra-host diversity and the highest evolutionary rate of all env fragments, consistent with this region being under a strong selective pressure for genetic variation. Overall, FIV env displayed relatively low intra-host diversity and evolved slowly in naturally infected cats. The maximum evolutionary rate was observed in the leader sequence of env. Although genetic stability is not necessarily a prerequisite for clinical stability, the higher genetic stability of FIV compared with human immunodeficiency virus might explain why many naturally infected cats do not progress rapidly to AIDS. PMID:25535323

  12. Dissecting the relationship between protein structure and sequence variation

    NASA Astrophysics Data System (ADS)

    Shahmoradi, Amir; Wilke, Claus; Wilke Lab Team

    2015-03-01

    Over the past decade several independent works have shown that some structural properties of proteins are capable of predicting protein evolution. The strength and significance of these structure-sequence relations, however, appear to vary widely among different proteins, with absolute correlation strengths ranging from 0 . 1 to 0 . 8 . Here we present the results from a comprehensive search for the potential biophysical and structural determinants of protein evolution by studying more than 200 structural and evolutionary properties in a dataset of 209 monomeric enzymes. We discuss the main protein characteristics responsible for the general patterns of protein evolution, and identify sequence divergence as the main determinant of the strengths of virtually all structure-evolution relationships, explaining ~ 10 - 30 % of observed variation in sequence-structure relations. In addition to sequence divergence, we identify several protein structural properties that are moderately but significantly coupled with the strength of sequence-structure relations. In particular, proteins with more homogeneous back-bone hydrogen bond energies, large fractions of helical secondary structures and low fraction of beta sheets tend to have the strongest sequence-structure relation. BEACON-NSF center for the study of evolution in action.

  13. Computational analysis of sequence selection mechanisms.

    PubMed

    Meyerguz, Leonid; Grasso, Catherine; Kleinberg, Jon; Elber, Ron

    2004-04-01

    Mechanisms leading to gene variations are responsible for the diversity of species and are important components of the theory of evolution. One constraint on gene evolution is that of protein foldability; the three-dimensional shapes of proteins must be thermodynamically stable. We explore the impact of this constraint and calculate properties of foldable sequences using 3660 structures from the Protein Data Bank. We seek a selection function that receives sequences as input, and outputs survival probability based on sequence fitness to structure. We compute the number of sequences that match a particular protein structure with energy lower than the native sequence, the density of the number of sequences, the entropy, and the "selection" temperature. The mechanism of structure selection for sequences longer than 200 amino acids is approximately universal. For shorter sequences, it is not. We speculate on concrete evolutionary mechanisms that show this behavior.

  14. Statistical distribution of amino acid sequences: a proof of Darwinian evolution.

    PubMed

    Eitner, Krystian; Koch, Uwe; Gaweda, Tomasz; Marciniak, Jedrzej

    2010-12-01

    The article presents results of the listing of the quantity of amino acids, dipeptides and tripeptides for all proteins available in the UNIPROT-TREMBL database and the listing for selected species and enzymes. UNIPROT-TREMBL contains protein sequences associated with computationally generated annotations and large-scale functional characterization. Due to the distinct metabolic pathways of amino acid syntheses and their physicochemical properties, the quantities of subpeptides in proteins vary. We have proved that the distribution of amino acids, dipeptides and tripeptides is statistical which confirms that the evolutionary biodiversity development model is subject to the theory of independent events. It seems interesting that certain short peptide combinations occur relatively rarely or even not at all. First, it confirms the Darwinian theory of evolution and second, it opens up opportunities for designing pharmaceuticals among rarely represented short peptide combinations. Furthermore, an innovative approach to the mass analysis of bioinformatic data is presented. eitner@amu.edu.pl Supplementary data are available at Bioinformatics online.

  15. Constraints on pre-main-sequence evolution from stellar pulsations

    NASA Astrophysics Data System (ADS)

    Casey, M. P.; Zwintz, K.; Guenther, D. B.

    2014-02-01

    Pulsating pre-main-sequence (PMS) stars afford the earliest opportunity in the lifetime of a star to which the concepts of asteroseismology can be applied. PMS stars should be structurally simpler than their evolved counterparts, thus (hopefully!) making any asteroseismic analysis relatively easier. Unfortunately, this isn't necessarily the case. The majority of these stars (around 80) are δ Scuti pulsators, with a couple of γ Doradus, γ Doradus - δ Scuti hybrids, and slowly pulsating B stars thrown into the mix. The majority of these stars have only been discovered within the last ten years, with the community still uncovering the richness of phenomena associated with these stars, many of which defy traditional asteroseismic analysis. A systematic asteroseismic analysis of all of the δ Scuti PMS stars was performed in order to get a better handle on the properties of these stars as a group. Some strange results have been found, including one star pulsating up to the theoretical acoustic cut-off frequency of the star, and a number of stars in which the most basic asteroseismic analysis suggests problems with the stars' positions in the Hertzsprung-Russell diagram. From this we get an idea of the\\break constraints - or lack thereof - that these results can put on PMS stellar evolution.

  16. Self-accelerating parabolic beams in quadratic nonlinear media

    NASA Astrophysics Data System (ADS)

    Dolev, Ido; Libster, Ana; Arie, Ady

    2012-09-01

    We present experimental observation of self-accelerating parabolic beams in quadratic nonlinear media. We show that the intensity peaks of the first and second harmonics are asynchronous with respect to one another in the two transverse coordinates. In addition, the two coupled harmonics have the same acceleration within and after the nonlinear medium. We also study the evolution of second harmonic accelerating beams inside the quadratic media and their correlation with theoretical beams.

  17. MicroRNA duplication accelerates the recruitment of new targets during vertebrate evolution

    PubMed Central

    Luo, Junjie; Wang, Yirong; Yuan, Jian

    2018-01-01

    The repertoire of miRNAs has considerably expanded during metazoan evolution, and duplication is an important mechanism for generating new functional miRNAs. However, relatively little is known about the functional divergence between paralogous miRNAs and the possible coevolution between duplicated miRNAs and the genomic contexts. By systematically examining small RNA expression profiles across various human tissues and interrogating the publicly available miRNA:mRNA pairing chimeras, we found that changes in expression patterns and targeting preferences are widespread for duplicated miRNAs in vertebrates. Both the empirical interactions and target predictions suggest that evolutionarily conserved homo-seed duplicated miRNAs pair with significantly higher numbers of target sites compared to the single-copy miRNAs. Our birth-and-death evolutionary analysis revealed that the new target sites of miRNAs experienced frequent gains and losses during function development. Our results suggest that a newly emerged target site has a higher probability to be functional and maintained by natural selection if it is paired to a seed shared by multiple paralogous miRNAs rather than being paired to a single-copy miRNA. We experimentally verified the divergence in target repression between two paralogous miRNAs by transfecting let-7a and let-7b mimics into kidney-derived cell lines of four mammalian species and measuring the resulting transcriptome alterations by extensive high-throughput sequencing. Our results also suggest that the gains and losses of let-7 target sites might be associated with the evolution of repressiveness of let-7 across mammalian species. PMID:29511046

  18. A Reevaluation of Rice Mitochondrial Evolution Based on the Complete Sequence of Male-Fertile and Male-Sterile Mitochondrial Genomes1[C][W][OA

    PubMed Central

    Bentolila, Stéphane; Stefanov, Stefan

    2012-01-01

    Plant mitochondrial genomes have features that distinguish them radically from their animal counterparts: a high rate of rearrangement, of uptake and loss of DNA sequences, and an extremely low point mutation rate. Perhaps the most unique structural feature of plant mitochondrial DNAs is the presence of large repeated sequences involved in intramolecular and intermolecular recombination. In addition, rare recombination events can occur across shorter repeats, creating rearrangements that result in aberrant phenotypes, including pollen abortion, which is known as cytoplasmic male sterility (CMS). Using next-generation sequencing, we pyrosequenced two rice (Oryza sativa) mitochondrial genomes that belong to the indica subspecies. One genome is normal, while the other carries the wild abortive-CMS. We find that numerous rearrangements in the rice mitochondrial genome occur even between close cytotypes during rice evolution. Unlike maize (Zea mays), a closely related species also belonging to the grass family, integration of plastid sequences did not play a role in the sequence divergence between rice cytotypes. This study also uncovered an excellent candidate for the wild abortive-CMS-encoding gene; like most of the CMS-associated open reading frames that are known in other species, this candidate was created via a rearrangement, is chimeric in structure, possesses predicted transmembrane domains, and coopted the promoter of a genuine mitochondrial gene. Our data give new insights into rice mitochondrial evolution, correcting previous reports. PMID:22128137

  19. Delayed Gratification Habitable Zones: When Deep Outer Solar System Regions Become Balmy During Post-Main Sequence Stellar Evolution

    NASA Astrophysics Data System (ADS)

    Stern, S. Alan

    2003-06-01

    Like all low- and moderate-mass stars, the Sun will burn as a red giant during its later evolution, generating of solar luminosities for some tens of millions of years. During this post-main sequence phase, the habitable (i.e., liquid water) thermal zone of our Solar System will lie in the region where Triton, Pluto-Charon, and Kuiper Belt objects orbit. Compared with the 1 AU habitable zone where Earth resides, this "delayed gratification habitable zone" (DGHZ) will enjoy a far less biologically hazardous environment - with lower harmful radiation levels from the Sun, and a far less destructive collisional environment. Objects like Triton, Pluto-Charon, and Kuiper Belt objects, which are known to be rich in both water and organics, will then become possible sites for biochemical and perhaps even biological evolution. The Kuiper Belt, with >105 objects >=50 km in radius and more than three times the combined surface area of the four terrestrial planets, provides numerous sites for possible evolution once the Sun's DGHZ reaches it. The Sun's DGHZ might be thought to only be of academic interest owing to its great separation from us in time. However, ~109 Milky Way stars burn as luminous red giants today. Thus, if icy-organic objects are common in the 20-50 AU zones of these stars, as they are in our Solar System (and as inferred in numerous main sequence stellar disk systems), then DGHZs may form a niche type of habitable zone that is likely to be numerically common in the Galaxy.

  20. Delayed gratification habitable zones: when deep outer solar system regions become balmy during post-main sequence stellar evolution.

    PubMed

    Stern, S Alan

    2003-01-01

    Like all low- and moderate-mass stars, the Sun will burn as a red giant during its later evolution, generating of solar luminosities for some tens of millions of years. During this post-main sequence phase, the habitable (i.e., liquid water) thermal zone of our Solar System will lie in the region where Triton, Pluto-Charon, and Kuiper Belt objects orbit. Compared with the 1 AU habitable zone where Earth resides, this "delayed gratification habitable zone" (DGHZ) will enjoy a far less biologically hazardous environment - with lower harmful radiation levels from the Sun, and a far less destructive collisional environment. Objects like Triton, Pluto-Charon, and Kuiper Belt objects, which are known to be rich in both water and organics, will then become possible sites for biochemical and perhaps even biological evolution. The Kuiper Belt, with >10(5) objects > or =50 km in radius and more than three times the combined surface area of the four terrestrial planets, provides numerous sites for possible evolution once the Sun's DGHZ reaches it. The Sun's DGHZ might be thought to only be of academic interest owing to its great separation from us in time. However, approximately 10(9) Milky Way stars burn as luminous red giants today. Thus, if icy-organic objects are common in the 20-50 AU zones of these stars, as they are in our Solar System (and as inferred in numerous main sequence stellar disk systems), then DGHZs may form a niche type of habitable zone that is likely to be numerically common in the Galaxy.

  1. The physics of evolution

    NASA Astrophysics Data System (ADS)

    Eigen, Manfred

    1988-12-01

    The Darwinian concept of evolution through natural selection has been revised and put on a solid physical basis, in a form which applies to self-replicable macromolecules. Two new concepts are introduced: sequence space and quasi-species. Evolutionary change in the DNA- or RNA-sequence of a gene can be mapped as a trajectory in a sequence space of dimension ν, where ν corresponds to the number of changeable positions in the genomic sequence. Emphasis, however, is shifted from the single surviving wildtype, a single point in the sequence space, to the complex structure of the mutant distribution that constitutes the quasi-species. Selection is equivalent to an establishment of the quasi-species in a localized region of sequence space, subject to threshold conditions for the error rate and sequence length. Arrival of a new mutant may violate the local threshold condition and thereby lead to a displacement of the quasi-species into a different region of sequence space. This transformation is similar to a phase transition; the dynamical equations that describe the quase-species have been shown to be analogous to those of the two-dimensional Ising model of ferromagnetism. The occurrence of a selectively advantageous mutant is biased by the particulars of the quasi-species distribution, whose mutants are populated according to their fitness relative to that of the wild-type. Inasmuch as fitness regions are connected (like mountain ridges) the evolutionary trajectory is guided to regions of optimal fitness. Evolution experiments in test tubes confirm this modification of the simple chance and law nature of the Darwinian concept. The results of the theory can also be applied to the construction of a machine that provides optimal conditions for a rapid evolution of functionally active macromolecules. An introduction to the physics of molecular evolution by the author has appeared recently.1 Detailed studies of the kinetics and mechanisms of replication of RNA, the most

  2. Structural insights into the evolution of a sexy protein: novel topology and restricted backbone flexibility in a hypervariable pheromone from the red-legged salamander, Plethodon shermani.

    PubMed

    Wilburn, Damien B; Bowen, Kathleen E; Doty, Kari A; Arumugam, Sengodagounder; Lane, Andrew N; Feldhoff, Pamela W; Feldhoff, Richard C

    2014-01-01

    In response to pervasive sexual selection, protein sex pheromones often display rapid mutation and accelerated evolution of corresponding gene sequences. For proteins, the general dogma is that structure is maintained even as sequence or function may rapidly change. This phenomenon is well exemplified by the three-finger protein (TFP) superfamily: a diverse class of vertebrate proteins co-opted for many biological functions - such as components of snake venoms, regulators of the complement system, and coordinators of amphibian limb regeneration. All of the >200 structurally characterized TFPs adopt the namesake "three-finger" topology. In male red-legged salamanders, the TFP pheromone Plethodontid Modulating Factor (PMF) is a hypervariable protein such that, through extensive gene duplication and pervasive sexual selection, individual male salamanders express more than 30 unique isoforms. However, it remained unclear how this accelerated evolution affected the protein structure of PMF. Using LC/MS-MS and multidimensional NMR, we report the 3D structure of the most abundant PMF isoform, PMF-G. The high resolution structural ensemble revealed a highly modified TFP structure, including a unique disulfide bonding pattern and loss of secondary structure, that define a novel protein topology with greater backbone flexibility in the third peptide finger. Sequence comparison, models of molecular evolution, and homology modeling together support that this flexible third finger is the most rapidly evolving segment of PMF. Combined with PMF sequence hypervariability, this structural flexibility may enhance the plasticity of PMF as a chemical signal by permitting potentially thousands of structural conformers. We propose that the flexible third finger plays a critical role in PMF:receptor interactions. As female receptors co-evolve, this flexibility may allow PMF to still bind its receptor(s) without the immediate need for complementary mutations. Consequently, this unique

  3. Modern Computational Techniques for the HMMER Sequence Analysis

    PubMed Central

    2013-01-01

    This paper focuses on the latest research and critical reviews on modern computing architectures, software and hardware accelerated algorithms for bioinformatics data analysis with an emphasis on one of the most important sequence analysis applications—hidden Markov models (HMM). We show the detailed performance comparison of sequence analysis tools on various computing platforms recently developed in the bioinformatics society. The characteristics of the sequence analysis, such as data and compute-intensive natures, make it very attractive to optimize and parallelize by using both traditional software approach and innovated hardware acceleration technologies. PMID:25937944

  4. Community Petascale Project for Accelerator Science and Simulation: Advancing Computational Science for Future Accelerators and Accelerator Technologies

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Spentzouris, P.; /Fermilab; Cary, J.

    The design and performance optimization of particle accelerators are essential for the success of the DOE scientific program in the next decade. Particle accelerators are very complex systems whose accurate description involves a large number of degrees of freedom and requires the inclusion of many physics processes. Building on the success of the SciDAC-1 Accelerator Science and Technology project, the SciDAC-2 Community Petascale Project for Accelerator Science and Simulation (ComPASS) is developing a comprehensive set of interoperable components for beam dynamics, electromagnetics, electron cooling, and laser/plasma acceleration modelling. ComPASS is providing accelerator scientists the tools required to enable the necessarymore » accelerator simulation paradigm shift from high-fidelity single physics process modeling (covered under SciDAC1) to high-fidelity multiphysics modeling. Our computational frameworks have been used to model the behavior of a large number of accelerators and accelerator R&D experiments, assisting both their design and performance optimization. As parallel computational applications, the ComPASS codes have been shown to make effective use of thousands of processors. ComPASS is in the first year of executing its plan to develop the next-generation HPC accelerator modeling tools. ComPASS aims to develop an integrated simulation environment that will utilize existing and new accelerator physics modules with petascale capabilities, by employing modern computing and solver technologies. The ComPASS vision is to deliver to accelerator scientists a virtual accelerator and virtual prototyping modeling environment, with the necessary multiphysics, multiscale capabilities. The plan for this development includes delivering accelerator modeling applications appropriate for each stage of the ComPASS software evolution. Such applications are already being used to address challenging problems in accelerator design and optimization. The Com

  5. Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis.

    PubMed

    Delaye, Luis; Ruiz-Ruiz, Susana; Calderon, Enrique; Tarazona, Sonia; Conesa, Ana; Moya, Andrés

    2018-06-01

    Pneumocystis species are ascomycete fungi adapted to live inside the lungs of mammals. These ascomycetes show extensive stenoxenism, meaning that each species of Pneumocystis infects a single species of host. Here, we study the effect exerted by natural selection on gene evolution in the genomes of three Pneumocystis species. We show that genes involved in host interaction evolve under positive selection. In the first place, we found strong evidence of episodic diversifying selection in Major surface glycoproteins (Msg). These proteins are located on the surface of Pneumocystis and are used for host attachment and probably for immune system evasion. Consistent with their function as antigens, most sites under diversifying selection in Msg code for residues with large relative surface accessibility areas. We also found evidence of positive selection in part of the cell machinery used to export Msg to the cell surface. Specifically, we found that genes participating in glycosylphosphatidylinositol (GPI) biosynthesis show an increased rate of nonsynonymous substitutions (dN) versus synonymous substitutions (dS). GPI is a molecule synthesized in the endoplasmic reticulum that is used to anchor proteins to membranes. We interpret the aforementioned findings as evidence of selective pressure exerted by the host immune system on Pneumocystis species, shaping the evolution of Msg and several proteins involved in GPI biosynthesis. We suggest that genome evolution in Pneumocystis is well described by the Red-Queen hypothesis whereby genes relevant for biotic interactions show accelerated rates of evolution.

  6. Bio++: a set of C++ libraries for sequence analysis, phylogenetics, molecular evolution and population genetics.

    PubMed

    Dutheil, Julien; Gaillard, Sylvain; Bazin, Eric; Glémin, Sylvain; Ranwez, Vincent; Galtier, Nicolas; Belkhir, Khalid

    2006-04-04

    A large number of bioinformatics applications in the fields of bio-sequence analysis, molecular evolution and population genetics typically share input/output methods, data storage requirements and data analysis algorithms. Such common features may be conveniently bundled into re-usable libraries, which enable the rapid development of new methods and robust applications. We present Bio++, a set of Object Oriented libraries written in C++. Available components include classes for data storage and handling (nucleotide/amino-acid/codon sequences, trees, distance matrices, population genetics datasets), various input/output formats, basic sequence manipulation (concatenation, transcription, translation, etc.), phylogenetic analysis (maximum parsimony, markov models, distance methods, likelihood computation and maximization), population genetics/genomics (diversity statistics, neutrality tests, various multi-locus analyses) and various algorithms for numerical calculus. Implementation of methods aims at being both efficient and user-friendly. A special concern was given to the library design to enable easy extension and new methods development. We defined a general hierarchy of classes that allow the developer to implement its own algorithms while remaining compatible with the rest of the libraries. Bio++ source code is distributed free of charge under the CeCILL general public licence from its website http://kimura.univ-montp2.fr/BioPP.

  7. Phylogeny, character evolution, and biogeography of Cuscuta (dodders; Convolvulaceae) inferred from coding plastid and nuclear sequences.

    PubMed

    García, Miguel A; Costea, Mihai; Kuzmina, Maria; Stefanović, Saša

    2014-04-01

    The parasitic genus Cuscuta, containing some 200 species circumscribed traditionally in three subgenera, is nearly cosmopolitan, occurring in a wide range of habitats and hosts. Previous molecular studies, on subgenera Grammica and Cuscuta, delimited major clades within these groups. However, the sequences used were unalignable among subgenera, preventing the phylogenetic comparison across the genus. We conducted a broad phylogenetic study using rbcL and nrLSU sequences covering the morphological, physiological, and geographical diversity of Cuscuta. We used parsimony methods to reconstruct ancestral states for taxonomically important characters. Biogeographical inferences were obtained using statistical and Bayesian approaches. Four well-supported major clades are resolved. Two of them correspond to subgenera Monogynella and Grammica. Subgenus Cuscuta is paraphyletic, with section Pachystigma sister to subgenus Grammica. Previously described cases of strongly supported discordance between plastid and nuclear phylogenies, interpreted as reticulation events, are confirmed here and three new cases are detected. Dehiscent fruits and globose stigmas are inferred as ancestral character states, whereas the ancestral style number is ambiguous. Biogeographical reconstructions suggest an Old World origin for the genus and subsequent spread to the Americas as a consequence of one long-distance dispersal. Hybridization may play an important yet underestimated role in the evolution of Cuscuta. Our results disagree with scenarios of evolution (polarity) previously proposed for several taxonomically important morphological characters, and with their usage and significance. While several cases of long-distance dispersal are inferred, vicariance or dispersal to adjacent areas emerges as the dominant biogeographical pattern.

  8. Methods of geometrical integration in accelerator physics

    NASA Astrophysics Data System (ADS)

    Andrianov, S. N.

    2016-12-01

    In the paper we consider a method of geometric integration for a long evolution of the particle beam in cyclic accelerators, based on the matrix representation of the operator of particles evolution. This method allows us to calculate the corresponding beam evolution in terms of two-dimensional matrices including for nonlinear effects. The ideology of the geometric integration introduces in appropriate computational algorithms amendments which are necessary for preserving the qualitative properties of maps presented in the form of the truncated series generated by the operator of evolution. This formalism extends both on polarized and intense beams. Examples of practical applications are described.

  9. Natural Selection and Adaptive Evolution of Leptin in the Ochotona Family Driven by the Cold Environmental Stress

    PubMed Central

    Yang, Jie; Wang, Zhen Long; Zhao, Xin Quan; Wang, De Peng; Qi, De Lin; Xu, Bao Hong; Ren, Yong Hong; Tian, Hui Fang

    2008-01-01

    Background Environmental stress can accelerate the evolutionary rate of specific stress-response proteins and create new functions specialized for different environments, enhancing an organism's fitness to stressful environments. Pikas (order Lagomorpha), endemic, non-hibernating mammals in the modern Holarctic Region, live in cold regions at either high altitudes or high latitudes and have a maximum distribution of species diversification confined to the Qinghai-Tibet Plateau. Variations in energy metabolism are remarkable for them living in cold environments. Leptin, an adipocyte-derived hormone, plays important roles in energy homeostasis. Methodology/Principal Findings To examine the extent of leptin variations within the Ochotona family, we cloned the entire coding sequence of pika leptin from 6 species in two regions (Qinghai-Tibet Plateau and Inner Mongolia steppe in China) and the leptin sequences of plateau pikas (O. curzonia) from different altitudes on Qinghai-Tibet Plateau. We carried out both DNA and amino acid sequence analyses in molecular evolution and compared modeled spatial structures. Our results show that positive selection (PS) acts on pika leptin, while nine PS sites located within the functionally significant segment 85-119 of leptin and one unique motif appeared only in pika lineages-the ATP synthase α and β subunit signature site. To reveal the environmental factors affecting sequence evolution of pika leptin, relative rate test was performed in pikas from different altitudes. Stepwise multiple regression shows that temperature is significantly and negatively correlated with the rates of non-synonymous substitution (Ka) and amino acid substitution (Aa), whereas altitude does not significantly affect synonymous substitution (Ks), Ka and Aa. Conclusions/Significance Our findings support the viewpoint that adaptive evolution may occur in pika leptin, which may play important roles in pikas' ecological adaptation to extreme environmental

  10. Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process.

    PubMed

    Wang, Lei; Li, Guoyuan; Ren, Ling; Kong, Xiangdong; Wang, Yugang; Han, Xiuguo; Jiang, Wenbo; Dai, Kerong; Yang, Ke; Hao, Yongqiang

    2017-01-01

    Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague-Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu 2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu 2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu 2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better

  11. Nano-copper-bearing stainless steel promotes fracture healing by accelerating the callus evolution process

    PubMed Central

    Kong, Xiangdong; Wang, Yugang; Han, Xiuguo; Jiang, Wenbo; Dai, Kerong; Yang, Ke; Hao, Yongqiang

    2017-01-01

    Treatment for fractures requires internal fixation devices, which are mainly produced from stainless steel or titanium alloy without biological functions. Therefore, we developed a novel nano-copper-bearing stainless steel with nano-sized copper-precipitation (317L-Cu SS). Based on previous studies, this work explores the effect of 317L-Cu SS on fracture healing; that is, proliferation, osteogenic differentiation, osteogenesis-related gene expression, and lysyl oxidase activity of human bone mesenchymal stem cells were detected in vitro. Sprague–Dawley rats were used to build an animal fracture model, and fracture healing and callus evolution were investigated by radiology (X-ray and micro-CT), histology (H&E, Masson, and safranin O/fast green staining), and histomorphometry. Further, the Cu2+ content and Runx2 level in the callus were determined, and local mechanical test of the fracture was performed to assess the healing quality. Our results revealed that 317L-Cu SS did not affect the proliferation of human bone mesenchymal stem cells, but promoted osteogenic differentiation and the expression of osteogenesis-related genes. In addition, 317L-Cu SS upregulated the lysyl oxidase activity. The X-ray and micro-CT results showed that the callus evolution efficiency and fracture healing speed were superior for 317L-Cu SS. Histological staining displayed large amounts of fibrous tissues at 3 weeks, and cartilage and new bone at 6 weeks. Further, histomorphometric analysis indicated that the callus possessed higher osteogenic efficiency at 6 weeks, and a high Cu2+ content and increased Runx2 expression were observed in the callus for 317L-Cu SS. Besides, the mechanical strength of the fracture site was much better than that of the control group. Overall, we conclude that 317L-Cu SS possesses the ability to increase Cu2+ content and promote osteogenesis in the callus, which could accelerate the callus evolution process and bone formation to provide faster and better

  12. The map-based genome sequence of Spirodela polyrhiza aligned with its chromosomes, a reference for karyotype evolution.

    PubMed

    Cao, Hieu Xuan; Vu, Giang Thi Ha; Wang, Wenqin; Appenroth, Klaus J; Messing, Joachim; Schubert, Ingo

    2016-01-01

    Duckweeds are aquatic monocotyledonous plants of potential economic interest with fast vegetative propagation, comprising 37 species with variable genome sizes (0.158-1.88 Gbp). The genomic sequence of Spirodela polyrhiza, the smallest and the most ancient duckweed genome, needs to be aligned to its chromosomes as a reference and prerequisite to study the genome and karyotype evolution of other duckweed species. We selected physically mapped bacterial artificial chromosomes (BACs) containing Spirodela DNA inserts with little or no repetitive elements as probes for multicolor fluorescence in situ hybridization (mcFISH), using an optimized BAC pooling strategy, to validate its physical map and correlate it with its chromosome complement. By consecutive mcFISH analyses, we assigned the originally assembled 32 pseudomolecules (supercontigs) of the genomic sequences to the 20 chromosomes of S. polyrhiza. A Spirodela cytogenetic map containing 96 BAC markers with an average distance of 0.89 Mbp was constructed. Using a cocktail of 41 BACs in three colors, all chromosome pairs could be individualized simultaneously. Seven ancestral blocks emerged from duplicated chromosome segments of 19 Spirodela chromosomes. The chromosomally integrated genome of S. polyrhiza and the established prerequisites for comparative chromosome painting enable future studies on the chromosome homoeology and karyotype evolution of duckweed species. © 2015 IPK Gatersleben. New Phytologist © 2015 New Phytologist Trust.

  13. A disruptive sequencer meets disruptive publishing.

    PubMed

    Loman, Nick; Goodwin, Sarah; Jansen, Hans; Loose, Matt

    2015-01-01

    Nanopore sequencing was recently made available to users in the form of the Oxford Nanopore MinION. Released to users through an early access programme, the MinION is made unique by its tiny form factor and ability to generate very long sequences from single DNA molecules. The platform is undergoing rapid evolution with three distinct nanopore types and five updates to library preparation chemistry in the last 18 months. To keep pace with the rapid evolution of this sequencing platform, and to provide a space where new analysis methods can be openly discussed, we present a new F1000Research channel devoted to updates to and analysis of nanopore sequence data.

  14. The evolution of WRKY transcription factors.

    PubMed

    Rinerson, Charles I; Rabara, Roel C; Tripathi, Prateek; Shen, Qingxi J; Rushton, Paul J

    2015-02-27

    The availability of increasing numbers of sequenced genomes has necessitated a re-evaluation of the evolution of the WRKY transcription factor family. Modern day plants descended from a charophyte green alga that colonized the land between 430 and 470 million years ago. The first charophyte genome sequence from Klebsormidium flaccidum filled a gap in the available genome sequences in the plant kingdom between unicellular green algae that typically have 1-3 WRKY genes and mosses that contain 30-40. WRKY genes have been previously found in non-plant species but their occurrence has been difficult to explain. Only two WRKY genes are present in the Klebsormidium flaccidum genome and the presence of a Group IIb gene was unexpected because it had previously been thought that Group IIb WRKY genes first appeared in mosses. We found WRKY transcription factor genes outside of the plant lineage in some diplomonads, social amoebae, fungi incertae sedis, and amoebozoa. This patchy distribution suggests that lateral gene transfer is responsible. These lateral gene transfer events appear to pre-date the formation of the WRKY groups in flowering plants. Flowering plants contain proteins with domains typical for both resistance (R) proteins and WRKY transcription factors. R protein-WRKY genes have evolved numerous times in flowering plants, each type being restricted to specific flowering plant lineages. These chimeric proteins contain not only novel combinations of protein domains but also novel combinations and numbers of WRKY domains. Once formed, R protein WRKY genes may combine different components of signalling pathways that may either create new diversity in signalling or accelerate signalling by short circuiting signalling pathways. We propose that the evolution of WRKY transcription factors includes early lateral gene transfers to non-plant organisms and the occurrence of algal WRKY genes that have no counterparts in flowering plants. We propose two alternative hypotheses

  15. Population genetic and evolution analysis of controversial genus Edwardsiella by multilocus sequence typing.

    PubMed

    Buján, Noemí; Balboa, Sabela; L Romalde, Jesús; E Toranzo, Alicia; Magariños, Beatriz

    2018-05-08

    At present, the genus Edwardsiella compiles five species: E. tarda, E. hoshinae, E. ictaluri, E. piscicida and E. anguillarum. Some species of this genus such us E. ictaluri and E. piscicida are important pathogens of numerous fish species. With the description of the two latter species, the phylogeny of Edwardsiella became more complicated. With the aim to clarify the relationships among all species in the genus, a multilocus sequence typing (MLST) approach was developed and applied to characterize 56 isolates and 6 reference strains belonging to the five Edwardsiella species. Moreover, several analyses based on the MLST scheme were performed to investigate the evolution within the genus, as well as the influence of recombination and mutation in the speciation. Edwardsiella isolates presented a high genetic variability reflected in the fourteen sequence types (ST) represented by a single isolates out of eighteen total ST. Mutation events were considerably more frequent than recombination, although both approximately equal influenced the genetic diversification. However, the speciation among species occurred mostly by recombination. Edwardsiella genus displays a non-clonal population structure with some degree of geographical isolation followed by a population expansion of E. piscicida. A database from this study was created and hosted on pubmlst.org (http://pubmlst.org/edwardsiella/). Copyright © 2018 Elsevier Inc. All rights reserved.

  16. Programming cells by multiplex genome engineering and accelerated evolution.

    PubMed

    Wang, Harris H; Isaacs, Farren J; Carr, Peter A; Sun, Zachary Z; Xu, George; Forest, Craig R; Church, George M

    2009-08-13

    The breadth of genomic diversity found among organisms in nature allows populations to adapt to diverse environments. However, genomic diversity is difficult to generate in the laboratory and new phenotypes do not easily arise on practical timescales. Although in vitro and directed evolution methods have created genetic variants with usefully altered phenotypes, these methods are limited to laborious and serial manipulation of single genes and are not used for parallel and continuous directed evolution of gene networks or genomes. Here, we describe multiplex automated genome engineering (MAGE) for large-scale programming and evolution of cells. MAGE simultaneously targets many locations on the chromosome for modification in a single cell or across a population of cells, thus producing combinatorial genomic diversity. Because the process is cyclical and scalable, we constructed prototype devices that automate the MAGE technology to facilitate rapid and continuous generation of a diverse set of genetic changes (mismatches, insertions, deletions). We applied MAGE to optimize the 1-deoxy-D-xylulose-5-phosphate (DXP) biosynthesis pathway in Escherichia coli to overproduce the industrially important isoprenoid lycopene. Twenty-four genetic components in the DXP pathway were modified simultaneously using a complex pool of synthetic DNA, creating over 4.3 billion combinatorial genomic variants per day. We isolated variants with more than fivefold increase in lycopene production within 3 days, a significant improvement over existing metabolic engineering techniques. Our multiplex approach embraces engineering in the context of evolution by expediting the design and evolution of organisms with new and improved properties.

  17. Evolution of complex dynamics

    NASA Astrophysics Data System (ADS)

    Wilds, Roy; Kauffman, Stuart A.; Glass, Leon

    2008-09-01

    We study the evolution of complex dynamics in a model of a genetic regulatory network. The fitness is associated with the topological entropy in a class of piecewise linear equations, and the mutations are associated with changes in the logical structure of the network. We compare hill climbing evolution, in which only mutations that increase the fitness are allowed, with neutral evolution, in which mutations that leave the fitness unchanged are allowed. The simple structure of the fitness landscape enables us to estimate analytically the rates of hill climbing and neutral evolution. In this model, allowing neutral mutations accelerates the rate of evolutionary advancement for low mutation frequencies. These results are applicable to evolution in natural and technological systems.

  18. Punctuated evolution and robustness in morphogenesis

    PubMed Central

    Grigoriev, D.; Reinitz, J.; Vakulenko, S.; Weber, A.

    2014-01-01

    This paper presents an analytic approach to the pattern stability and evolution problem in morphogenesis. The approach used here is based on the ideas from the gene and neural network theory. We assume that gene networks contain a number of small groups of genes (called hubs) controlling morphogenesis process. Hub genes represent an important element of gene network architecture and their existence is empirically confirmed. We show that hubs can stabilize morphogenetic pattern and accelerate the morphogenesis. The hub activity exhibits an abrupt change depending on the mutation frequency. When the mutation frequency is small, these hubs suppress all mutations and gene product concentrations do not change, thus, the pattern is stable. When the environmental pressure increases and the population needs new genotypes, the genetic drift and other effects increase the mutation frequency. For the frequencies that are larger than a critical amount the hubs turn off; and as a result, many mutations can affect phenotype. This effect can serve as an engine for evolution. We show that this engine is very effective: the evolution acceleration is an exponential function of gene redundancy. Finally, we show that the Eldredge-Gould concept of punctuated evolution results from the network architecture, which provides fast evolution, control of evolvability, and pattern robustness. To describe analytically the effect of exponential acceleration, we use mathematical methods developed recently for hard combinatorial problems, in particular, for so-called k-SAT problem, and numerical simulations. PMID:24996115

  19. Multiplex sequencing of plant chloroplast genomes using Solexa sequencing-by-synthesis technology

    Treesearch

    Richard Cronn; Aaron Liston; Matthew Parks; David S. Gernandt; Rongkun Shen; Todd Mockler

    2008-01-01

    Organellar DNA sequences are widely used in evolutionary and population genetic studies; however, the conservative nature of chloroplast gene and genome evolution often limits phylogenetic resolution and statistical power. To gain maximal access to the historical record contained within chloroplast genomes, we have adapted multiplex sequencing-by-synthesis (MSBS) to...

  20. Molecular evolution of cyclin proteins in animals and fungi

    PubMed Central

    2011-01-01

    Background The passage through the cell cycle is controlled by complexes of cyclins, the regulatory units, with cyclin-dependent kinases, the catalytic units. It is also known that cyclins form several families, which differ considerably in primary structure from one eukaryotic organism to another. Despite these lines of evidence, the relationship between the evolution of cyclins and their function is an open issue. Here we present the results of our study on the molecular evolution of A-, B-, D-, E-type cyclin proteins in animals and fungi. Results We constructed phylogenetic trees for these proteins, their ancestral sequences and analyzed patterns of amino acid replacements. The analysis of infrequently fixed atypical amino acid replacements in cyclins evidenced that accelerated evolution proceeded predominantly during paralog duplication or after it in animals and fungi and that it was related to aromorphic changes in animals. It was shown also that evolutionary flexibility of cyclin function may be provided by consequential reorganization of regions on protein surface remote from CDK binding sites in animal and fungal cyclins and by functional differentiation of paralogous cyclins formed in animal evolution. Conclusions The results suggested that changes in the number and/or nature of cyclin-binding proteins may underlie the evolutionary role of the alterations in the molecular structure of cyclins and their involvement in diverse molecular-genetic events. PMID:21798004

  1. The Contribution of Genetic Recombination to CRISPR Array Evolution

    PubMed Central

    Kupczok, Anne; Landan, Giddy; Dagan, Tal

    2015-01-01

    CRISPR (clustered regularly interspaced short palindromic repeats) is a microbial immune system against foreign DNA. Recognition sequences (spacers) encoded within the CRISPR array mediate the immune reaction in a sequence-specific manner. The known mechanisms for the evolution of CRISPR arrays include spacer acquisition from foreign DNA elements at the time of invasion and array erosion through spacer deletion. Here, we consider the contribution of genetic recombination between homologous CRISPR arrays to the evolution of spacer repertoire. Acquisition of spacers from exogenic arrays via recombination may confer the recipient with immunity against unencountered antagonists. For this purpose, we develop a novel method for the detection of recombination in CRISPR arrays by modeling the spacer order in arrays from multiple strains from the same species. Because the evolutionary signal of spacer recombination may be similar to that of pervasive spacer deletions or independent spacer acquisition, our method entails a robustness analysis of the recombination inference by a statistical comparison to resampled and perturbed data sets. We analyze CRISPR data sets from four bacterial species: two Gammaproteobacteria species harboring CRISPR type I and two Streptococcus species harboring CRISPR type II loci. We find that CRISPR array evolution in Escherichia coli and Streptococcus agalactiae can be explained solely by vertical inheritance and differential spacer deletion. In Pseudomonas aeruginosa, we find an excess of single spacers potentially incorporated into the CRISPR locus during independent acquisition events. In Streptococcus thermophilus, evidence for spacer acquisition by recombination is present in 5 out of 70 strains. Genetic recombination has been proposed to accelerate adaptation by combining beneficial mutations that arose in independent lineages. However, for most species under study, we find that CRISPR evolution is shaped mainly by spacer acquisition and

  2. A Generative Angular Model of Protein Structure Evolution

    PubMed Central

    Golden, Michael; García-Portugués, Eduardo; Sørensen, Michael; Mardia, Kanti V.; Hamelryck, Thomas; Hein, Jotun

    2017-01-01

    Abstract Recently described stochastic models of protein evolution have demonstrated that the inclusion of structural information in addition to amino acid sequences leads to a more reliable estimation of evolutionary parameters. We present a generative, evolutionary model of protein structure and sequence that is valid on a local length scale. The model concerns the local dependencies between sequence and structure evolution in a pair of homologous proteins. The evolutionary trajectory between the two structures in the protein pair is treated as a random walk in dihedral angle space, which is modeled using a novel angular diffusion process on the two-dimensional torus. Coupling sequence and structure evolution in our model allows for modeling both “smooth” conformational changes and “catastrophic” conformational jumps, conditioned on the amino acid changes. The model has interpretable parameters and is comparatively more realistic than previous stochastic models, providing new insights into the relationship between sequence and structure evolution. For example, using the trained model we were able to identify an apparent sequence–structure evolutionary motif present in a large number of homologous protein pairs. The generative nature of our model enables us to evaluate its validity and its ability to simulate aspects of protein evolution conditioned on an amino acid sequence, a related amino acid sequence, a related structure or any combination thereof. PMID:28453724

  3. Metabolic acceleration and the evolution of human brain size and life history.

    PubMed

    Pontzer, Herman; Brown, Mary H; Raichlen, David A; Dunsworth, Holly; Hare, Brian; Walker, Kara; Luke, Amy; Dugas, Lara R; Durazo-Arvizu, Ramon; Schoeller, Dale; Plange-Rhule, Jacob; Bovet, Pascal; Forrester, Terrence E; Lambert, Estelle V; Thompson, Melissa Emery; Shumaker, Robert W; Ross, Stephen R

    2016-05-19

    Humans are distinguished from the other living apes in having larger brains and an unusual life history that combines high reproductive output with slow childhood growth and exceptional longevity. This suite of derived traits suggests major changes in energy expenditure and allocation in the human lineage, but direct measures of human and ape metabolism are needed to compare evolved energy strategies among hominoids. Here we used doubly labelled water measurements of total energy expenditure (TEE; kcal day(-1)) in humans, chimpanzees, bonobos, gorillas and orangutans to test the hypothesis that the human lineage has experienced an acceleration in metabolic rate, providing energy for larger brains and faster reproduction without sacrificing maintenance and longevity. In multivariate regressions including body size and physical activity, human TEE exceeded that of chimpanzees and bonobos, gorillas and orangutans by approximately 400, 635 and 820 kcal day(-1), respectively, readily accommodating the cost of humans' greater brain size and reproductive output. Much of the increase in TEE is attributable to humans' greater basal metabolic rate (kcal day(-1)), indicating increased organ metabolic activity. Humans also had the greatest body fat percentage. An increased metabolic rate, along with changes in energy allocation, was crucial in the evolution of human brain size and life history.

  4. Novel phytochrome sequences in Arabidopsis thaliana: Structure, evolution, and differential expression of a plant regulatory photoreceptor family

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sharrock, R.A.; Quail, P.H.

    1989-01-01

    Phytochrome is a plant regulatory photoreceptor that mediates red light effects on a wide variety of physiological and molecular responses. DNA blot analysis indicates that the Arabidopsis thaliana genome contains four to five phytochrome-related gene sequences. The authors have isolated and sequenced cDNA clones corresponding to three of these genes and have deduced the amino acid sequence of the full-length polypeptide encoded in each case. One of these proteins (phyA) shows 65-80% amino acid sequence identity with the major, etiolated-tissue phytochrome apoproteins described previously in other plant species. The other two polypeptides (phyB and phyC) are unique in that theymore » have low sequence identity with each other, with phyA, and with all previously described phytochromes. The phyA, phyB, and phyC proteins are of similar molecular mass, have related hydropathic profiles, and contain a conserved chromophore attachment region. However, the sequence comparison data indicate that the three phy genes diverged early in plant evolution, well before the divergence of the two major groups of angiosperms, the monocots and dicots. The steady-state level of the phyA transcript is high in dark-grown A. thaliana seedlings and is down-regulated by light. In contrast, the phyB and phyC transcripts are present at lower levels and are not strongly light-regulated. These findings indicate that the red/far red light-responsive phytochrome photoreceptor system in A. thaliana, and perhaps in all higher plants, consists of a family of chromoproteins that are heterogeneous in structure and regulation.« less

  5. An extended car-following model considering the acceleration derivative in some typical traffic environments

    NASA Astrophysics Data System (ADS)

    Zhou, Tong; Chen, Dong; Liu, Weining

    2018-03-01

    Based on the full velocity difference and acceleration car-following model, an extended car-following model is proposed by considering the vehicle’s acceleration derivative. The stability condition is given by applying the control theory. Considering some typical traffic environments, the results of theoretical analysis and numerical simulation show the extended model has a more actual acceleration of string vehicles than that of the previous models in starting process, stopping process and sudden brake. Meanwhile, the traffic jams more easily occur when the coefficient of vehicle’s acceleration derivative increases, which is presented by space-time evolution. The results confirm that the vehicle’s acceleration derivative plays an important role in the traffic jamming transition and the evolution of traffic congestion.

  6. Rapid sequence evolution of street rabies glycoprotein is related to the highly heterogeneous nature of the viral population.

    PubMed

    Benmansour, A; Brahimi, M; Tuffereau, C; Coulon, P; Lafay, F; Flamand, A

    1992-03-01

    The sequence of the glycoprotein gene of a street rabies virus was determined directly using fragments of a rabid dog brain after PCR amplification. Compared with that of the prototype strain CVS, this sequence displayed 10% divergence in overall amino acid composition. However only 6% divergence was noted in the ectodomain suggesting that structural constraints are exerted on this portion of the glycoprotein. A human strain isolated on cell culture from the saliva of a patient with clinical rabies had only five amino acid differences with the canine isolate, an indication of their close relatedness. These differences could have originated during transmission from dog to dog, or from dog to man, or during isolation on cell culture; they are nonetheless indicative of a genetic evolution of street rabies virus. This evolution was further evidenced by the selection of cell-adapted variants which displayed new amino acid substitutions in the glycoprotein. One of them concerned antigenic site III where arginine at position 333 was replaced by glutamine. As expected this substitution conferred resistance to a site IIIa monoclonal antibody (MAb), but surprisingly did not abolish neurovirulence for adult mice. However, a decrease in the neurovirulence of the cell-adapted variant in the presence of a site IIIa specific MAb was noted, suggesting that neurovirulence was due to a subpopulation neutralizable by the MAb. Simultaneous presence of both the parental and variant sequences was indeed evidenced in the brain of a mouse inoculated with the cell-adapted variant; during multiplication in the mouse brain, the frequency of the parental sequence rose from less than 10% to nearly 50%, indicating the selective advantage conferred by arginine 333 in nervous tissue. Altogether these results were suggestive of an intrinsic heterogeneity of street rabies virus. This heterogeneity was further demonstrated by the sequencing of molecular clones of the glycoprotein gene, which

  7. Cyclotrons and FFAG Accelerators as Drivers for ADS

    DOE PAGES

    Calabretta, Luciano; Méot, François

    2015-01-01

    Our review summarizes projects and studies on circular accelerators proposed for driving subcritical reactors. The early isochronous cyclotron cascades, proposed about 20 years ago, and the evolution of these layouts up to the most recent solutions or designs based on cyclotrons and fixed field alternating gradient accelerators, are reported. Additionally, the newest ideas and their prospects for development are discussed.

  8. Evolution Models of Helium White Dwarf–Main-sequence Star Merger Remnants

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Xianfei; Bi, Shaolan; Hall, Philip D.

    It is predicted that orbital decay by gravitational-wave radiation and tidal interaction will cause some close binary stars to merge within a Hubble time. The merger of a helium-core white dwarf with a main-sequence (MS) star can produce a red giant branch star that has a low-mass hydrogen envelope when helium is ignited and thus become a hot subdwarf. Because detailed calculations have not been made, we compute post-merger models with a stellar evolution code. We find the evolutionary paths available to merger remnants and find the pre-merger conditions that lead to the formation of hot subdwarfs. We find thatmore » some such mergers result in the formation of stars with intermediate helium-rich surfaces. These stars later develop helium-poor surfaces owing to diffusion. Combining our results with a model population and comparing to observed stars, we find that some observed intermediate helium-rich hot subdwarfs can be explained as the remnants of the mergers of helium-core white dwarfs with low-mass MS stars.« less

  9. VDJ-Seq: Deep Sequencing Analysis of Rearranged Immunoglobulin Heavy Chain Gene to Reveal Clonal Evolution Patterns of B Cell Lymphoma.

    PubMed

    Jiang, Yanwen; Nie, Kui; Redmond, David; Melnick, Ari M; Tam, Wayne; Elemento, Olivier

    2015-12-28

    Understanding tumor clonality is critical to understanding the mechanisms involved in tumorigenesis and disease progression. In addition, understanding the clonal composition changes that occur within a tumor in response to certain micro-environment or treatments may lead to the design of more sophisticated and effective approaches to eradicate tumor cells. However, tracking tumor clonal sub-populations has been challenging due to the lack of distinguishable markers. To address this problem, a VDJ-seq protocol was created to trace the clonal evolution patterns of diffuse large B cell lymphoma (DLBCL) relapse by exploiting VDJ recombination and somatic hypermutation (SHM), two unique features of B cell lymphomas. In this protocol, Next-Generation sequencing (NGS) libraries with indexing potential were constructed from amplified rearranged immunoglobulin heavy chain (IgH) VDJ region from pairs of primary diagnosis and relapse DLBCL samples. On average more than half million VDJ sequences per sample were obtained after sequencing, which contain both VDJ rearrangement and SHM information. In addition, customized bioinformatics pipelines were developed to fully utilize sequence information for the characterization of IgH-VDJ repertoire within these samples. Furthermore, the pipeline allows the reconstruction and comparison of the clonal architecture of individual tumors, which enables the examination of the clonal heterogeneity within the diagnosis tumors and deduction of clonal evolution patterns between diagnosis and relapse tumor pairs. When applying this analysis to several diagnosis-relapse pairs, we uncovered key evidence that multiple distinctive tumor evolutionary patterns could lead to DLBCL relapse. Additionally, this approach can be expanded into other clinical aspects, such as identification of minimal residual disease, monitoring relapse progress and treatment response, and investigation of immune repertoires in non-lymphoma contexts.

  10. Sequence and expression variation in SUPPRESSOR of OVEREXPRESSION of CONSTANS 1 (SOC1): homeolog evolution in Indian Brassicas.

    PubMed

    Sri, Tanu; Mayee, Pratiksha; Singh, Anandita

    2015-09-01

    Whole genome sequence analyses allow unravelling such evolutionary consequences of meso-triplication event in Brassicaceae (∼14-20 million years ago (MYA)) as differential gene fractionation and diversification in homeologous sub-genomes. This study presents a simple gene-centric approach involving microsynteny and natural genetic variation analysis for understanding SUPPRESSOR of OVEREXPRESSION of CONSTANS 1 (SOC1) homeolog evolution in Brassica. Analysis of microsynteny in Brassica rapa homeologous regions containing SOC1 revealed differential gene fractionation correlating to reported fractionation status of sub-genomes of origin, viz. least fractionated (LF), moderately fractionated 1 (MF1) and most fractionated (MF2), respectively. Screening 18 cultivars of 6 Brassica species led to the identification of 8 genomic and 27 transcript variants of SOC1, including splice-forms. Co-occurrence of both interrupted and intronless SOC1 genes was detected in few Brassica species. In silico analysis characterised Brassica SOC1 as MADS intervening, K-box, C-terminal (MIKC(C)) transcription factor, with highly conserved MADS and I domains relative to K-box and C-terminal domain. Phylogenetic analyses and multiple sequence alignments depicting shared pattern of silent/non-silent mutations assigned Brassica SOC1 homologs into groups based on shared diploid base genome. In addition, a sub-genome structure in uncharacterised Brassica genomes was inferred. Expression analysis of putative MF2 and LF (Brassica diploid base genome A (AA)) sub-genome-specific SOC1 homeologs of Brassica juncea revealed near identical expression pattern. However, MF2-specific homeolog exhibited significantly higher expression implying regulatory diversification. In conclusion, evidence for polyploidy-induced sequence and regulatory evolution in Brassica SOC1 is being presented wherein differential homeolog expression is implied in functional diversification.

  11. The complete genome sequence of Lactobacillus bulgaricus reveals extensive and ongoing reductive evolution.

    PubMed

    van de Guchte, M; Penaud, S; Grimaldi, C; Barbe, V; Bryson, K; Nicolas, P; Robert, C; Oztas, S; Mangenot, S; Couloux, A; Loux, V; Dervyn, R; Bossy, R; Bolotin, A; Batto, J-M; Walunas, T; Gibrat, J-F; Bessières, P; Weissenbach, J; Ehrlich, S D; Maguin, E

    2006-06-13

    Lactobacillus delbrueckii ssp. bulgaricus (L. bulgaricus) is a representative of the group of lactic acid-producing bacteria, mainly known for its worldwide application in yogurt production. The genome sequence of this bacterium has been determined and shows the signs of ongoing specialization, with a substantial number of pseudogenes and incomplete metabolic pathways and relatively few regulatory functions. Several unique features of the L. bulgaricus genome support the hypothesis that the genome is in a phase of rapid evolution. (i) Exceptionally high numbers of rRNA and tRNA genes with regard to genome size may indicate that the L. bulgaricus genome has known a recent phase of important size reduction, in agreement with the observed high frequency of gene inactivation and elimination; (ii) a much higher GC content at codon position 3 than expected on the basis of the overall GC content suggests that the composition of the genome is evolving toward a higher GC content; and (iii) the presence of a 47.5-kbp inverted repeat in the replication termination region, an extremely rare feature in bacterial genomes, may be interpreted as a transient stage in genome evolution. The results indicate the adaptation of L. bulgaricus from a plant-associated habitat to the stable protein and lactose-rich milk environment through the loss of superfluous functions and protocooperation with Streptococcus thermophilus.

  12. The Genomic Evolution of Prostate Cancer

    DTIC Science & Technology

    2017-06-01

    management and grant writing skills. 15. SUBJECT TERMS Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing 16...aggressive disease, it is unclear if the genetic alterations more common in late disease are present early on, but at low frequency, or if they only...from localized to metastatic prostate cancer. 2. KEYWORDS: Cancer genetics , tumor evolution, tumor heterogeneity, prostate cancer, exome sequencing

  13. Time-Sampled Population Sequencing Reveals the Interplay of Selection and Genetic Drift in Experimental Evolution of Potato Virus Y

    PubMed Central

    2017-01-01

    ABSTRACT RNA viruses are one of the fastest-evolving biological entities. Within their hosts, they exist as genetically diverse populations (i.e., viral mutant swarms), which are sculpted by different evolutionary mechanisms, such as mutation, natural selection, and genetic drift, and also the interactions between genetic variants within the mutant swarms. To elucidate the mechanisms that modulate the population diversity of an important plant-pathogenic virus, we performed evolution experiments with Potato virus Y (PVY) in potato genotypes that differ in their defense response against the virus. Using deep sequencing of small RNAs, we followed the temporal dynamics of standing and newly generated variations in the evolving viral lineages. A time-sampled approach allowed us to (i) reconstruct theoretical haplotypes in the starting population by using clustering of single nucleotide polymorphisms' trajectories and (ii) use quantitative population genetics approaches to estimate the contribution of selection and genetic drift, and their interplay, to the evolution of the virus. We detected imprints of strong selective sweeps and narrow genetic bottlenecks, followed by the shift in frequency of selected haplotypes. Comparison of patterns of viral evolution in differently susceptible host genotypes indicated possible diversifying evolution of PVY in the less-susceptible host (efficient in the accumulation of salicylic acid). IMPORTANCE High diversity of within-host populations of RNA viruses is an important aspect of their biology, since they represent a reservoir of genetic variants, which can enable quick adaptation of viruses to a changing environment. This study focuses on an important plant virus, Potato virus Y, and describes, at high resolution, temporal changes in the structure of viral populations within different potato genotypes. A novel and easy-to-implement computational approach was established to cluster single nucleotide polymorphisms into viral

  14. The Contribution of Genetic Recombination to CRISPR Array Evolution.

    PubMed

    Kupczok, Anne; Landan, Giddy; Dagan, Tal

    2015-06-16

    CRISPR (clustered regularly interspaced short palindromic repeats) is a microbial immune system against foreign DNA. Recognition sequences (spacers) encoded within the CRISPR array mediate the immune reaction in a sequence-specific manner. The known mechanisms for the evolution of CRISPR arrays include spacer acquisition from foreign DNA elements at the time of invasion and array erosion through spacer deletion. Here, we consider the contribution of genetic recombination between homologous CRISPR arrays to the evolution of spacer repertoire. Acquisition of spacers from exogenic arrays via recombination may confer the recipient with immunity against unencountered antagonists. For this purpose, we develop a novel method for the detection of recombination in CRISPR arrays by modeling the spacer order in arrays from multiple strains from the same species. Because the evolutionary signal of spacer recombination may be similar to that of pervasive spacer deletions or independent spacer acquisition, our method entails a robustness analysis of the recombination inference by a statistical comparison to resampled and perturbed data sets. We analyze CRISPR data sets from four bacterial species: two Gammaproteobacteria species harboring CRISPR type I and two Streptococcus species harboring CRISPR type II loci. We find that CRISPR array evolution in Escherichia coli and Streptococcus agalactiae can be explained solely by vertical inheritance and differential spacer deletion. In Pseudomonas aeruginosa, we find an excess of single spacers potentially incorporated into the CRISPR locus during independent acquisition events. In Streptococcus thermophilus, evidence for spacer acquisition by recombination is present in 5 out of 70 strains. Genetic recombination has been proposed to accelerate adaptation by combining beneficial mutations that arose in independent lineages. However, for most species under study, we find that CRISPR evolution is shaped mainly by spacer acquisition and

  15. Advances for studying clonal evolution in cancer.

    PubMed

    Ding, Li; Raphael, Benjamin J; Chen, Feng; Wendl, Michael C

    2013-11-01

    The "clonal evolution" model of cancer emerged and "evolved" amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other's survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  16. Toward a mechanistic understanding of the damage evolution of SnAgCu solder joints in accelerated thermal cycling test

    NASA Astrophysics Data System (ADS)

    Mahin Shirazi, Sam

    Accelerated thermal cycling (ATC) tests are the most commonly used tests for the thermo-mechanical performance assessment of microelectronics assemblies. Currently used reliability models have failed to incorporate the microstructural dependency of lead free solder joint behavior and its microstructure evolution during cycling. Thus, it is essential to have a mechanistic understanding of the effect of cycling parameters on damage evolution and failure of lead free solder joints in ATC. Recrystallization has been identified as the damage rate controlling mechanism in ATC. Usually it takes 1/3 of life for completion of recrystallization regardless of cycling parameters. Thus, the life of the solder joints can be predicted by estimating global recrystallization. The objective of the first part of the study was to examine whether the damage scenario applies in service is the same as the harsh thermal cycling tests (i.e. 0/100 °C and -40/125 °C) commonly used in industry. Microstructure analysis results on a variety of lead free solder SnAgCu assemblies subjected to the both harsh (0/100 °C) and mild (20/80 °C) ATC confirmed similar failure mechanism under the both testing conditions. Sn grain morphology (interlaced versus beach ball) has a significant effect on the thermo-mechanical performance (and thus the model) of the lead free solder joints. The longer thermal cycling lifetime observed in the interlaced solder joints subjected to the ATC compared to the beach ball structure was correlated to the different initial microstructure and the microstructure evolution during cycling. For the modeling proposes, the present study was focused on Sn-Ag-Cu solder joints with either a single Sn grain or beach ball structure. Microstructural analysis results of the simulated thermal cycling experiment revealed that, the life can be approximated as determined by the accumulation of a certain amount of work during the high temperature dwells. Finally the effect of precipitates

  17. AMPLIFICATION OF RIBOSOMAL RNA SEQUENCES

    EPA Science Inventory

    This book chapter offers an overview of the use of ribosomal RNA sequences. A history of the technology traces the evolution of techniques to measure bacterial phylogenetic relationships and recent advances in obtaining rRNA sequence information. The manual also describes procedu...

  18. A phylogeny of the bears (Ursidae) inferred from complete sequences of three mitochondrial genes.

    PubMed

    Talbot, S L; Shields, G F

    1996-06-01

    Complete sequences of DNA are described for the cytochrome b tRNA(Thr) and tRNA(Pro) genes of mitochondria of four extant species of ursids and compared to sequences of four other species of ursids previously studied by us. Phylogenetic analyses indicate that the giant panda and the spectacled bear are the basal taxa of the ursid radiation. The ursines, a group which includes the sun bear, sloth bear, American black bear, Asiatic black bear, brown bear, and polar bear, experienced a rapid radiation during the mid Pliocene to early Pleistocene. The Asiatic black bear and American black bear are sister taxa. The brown bear and polar bear are the most recently derived of the ursines, with the polar bear originating from within a clade of brown bears during the Pleistocene. This paraphyletic association suggests that the rate of morphological evolution may be accelerated relative to that of molecular evolution when a new ecological niche is occupied. Calibration of the corrected average number of nucleotide differences per site with the fossil record indicates that transitions at third positions of codons in the ursid cytochrome b gene occur at a rate of approximately 6% per million years, which is considerably slower than comparable values reported for other species of mammal.

  19. A Bayesian compound stochastic process for modeling nonstationary and nonhomogeneous sequence evolution.

    PubMed

    Blanquart, Samuel; Lartillot, Nicolas

    2006-11-01

    Variations of nucleotidic composition affect phylogenetic inference conducted under stationary models of evolution. In particular, they may cause unrelated taxa sharing similar base composition to be grouped together in the resulting phylogeny. To address this problem, we developed a nonstationary and nonhomogeneous model accounting for compositional biases. Unlike previous nonstationary models, which are branchwise, that is, assume that base composition only changes at the nodes of the tree, in our model, the process of compositional drift is totally uncoupled from the speciation events. In addition, the total number of events of compositional drift distributed across the tree is directly inferred from the data. We implemented the method in a Bayesian framework, relying on Markov Chain Monte Carlo algorithms, and applied it to several nucleotidic data sets. In most cases, the stationarity assumption was rejected in favor of our nonstationary model. In addition, we show that our method is able to resolve a well-known artifact. By Bayes factor evaluation, we compared our model with 2 previously developed nonstationary models. We show that the coupling between speciations and compositional shifts inherent to branchwise models may lead to an overparameterization, resulting in a lesser fit. In some cases, this leads to incorrect conclusions, concerning the nature of the compositional biases. In contrast, our compound model more flexibly adapts its effective number of parameters to the data sets under investigation. Altogether, our results show that accounting for nonstationary sequence evolution may require more elaborate and more flexible models than those currently used.

  20. Acceleration and propagation of cosmic rays

    NASA Astrophysics Data System (ADS)

    Fransson, C.; Epstein, R. I.

    1980-11-01

    Two general categories of cosmic ray models are discussed, concomitant acceleration and propagation (CAP) models and sequential acceleration and propagation (SAP) models. These normally correspond to the cosmic rays being continuously accelerated in the interstellar medium or being rapidly produced by discrete sources or strong shock waves, respectively. For the CAP models it is found that the ratio of the predominantly secondary nuclei (Li + Be + B + N) to the predominantly primary nuclei (C + O) varies by less than a factor of 1.5 between 1 and 100 GeV per nucleon. This is at variance with current measurements. It thus appears that the evolution of cosmic rays is best described by SAP models.

  1. Observations of the Coronal Mass Ejection with a Complex Acceleration Profile

    NASA Astrophysics Data System (ADS)

    Reva, A. A.; Kirichenko, A. S.; Ulyanov, A. S.; Kuzin, S. V.

    2017-12-01

    We study the coronal mass ejection (CME) with a complex acceleration profile. The event occurred on 2009 April 23. It had an impulsive acceleration phase, an impulsive deceleration phase, and a second impulsive acceleration phase. During its evolution, the CME showed signatures of different acceleration mechanisms: kink instability, prominence drainage, flare reconnection, and a CME–CME collision. The special feature of the observations is the usage of the TESIS EUV telescope. The instrument could image the solar corona in the Fe 171 Å line up to a distance of 2 {R}ȯ from the center of the Sun. This allows us to trace the CME up to the LASCO/C2 field of view without losing the CME from sight. The onset of the CME was caused by kink instability. The mass drainage occurred after the kink instability. The mass drainage played only an auxiliary role: it decreased the CME mass, which helped to accelerate the CME. The first impulsive acceleration phase was caused by the flare reconnection. We observed the two-ribbon flare and an increase of the soft X-ray flux during the first impulsive acceleration phase. The impulsive deceleration and the second impulsive acceleration phases were caused by the CME–CME collision. The studied event shows that CMEs are complex phenomena that cannot be explained with only one acceleration mechanism. We should seek a combination of different mechanisms that accelerate CMEs at different stages of their evolution.

  2. Clonal evolution revealed by whole genome sequencing in a case of primary myelofibrosis transformed to secondary acute myeloid leukemia.

    PubMed

    Engle, E K; Fisher, D A C; Miller, C A; McLellan, M D; Fulton, R S; Moore, D M; Wilson, R K; Ley, T J; Oh, S T

    2015-04-01

    Clonal architecture in myeloproliferative neoplasms (MPNs) is poorly understood. Here we report genomic analyses of a patient with primary myelofibrosis (PMF) transformed to secondary acute myeloid leukemia (sAML). Whole genome sequencing (WGS) was performed on PMF and sAML diagnosis samples, with skin included as a germline surrogate. Deep sequencing validation was performed on the WGS samples and an additional sample obtained during sAML remission/relapsed PMF. Clustering analysis of 649 validated somatic single-nucleotide variants revealed four distinct clonal groups, each including putative driver mutations. The first group (including JAK2 and U2AF1), representing the founding clone, included mutations with high frequency at all three disease stages. The second clonal group (including MYB) was present only in PMF, suggesting the presence of a clone that was dispensable for transformation. The third group (including ASXL1) contained mutations with low frequency in PMF and high frequency in subsequent samples, indicating evolution of the dominant clone with disease progression. The fourth clonal group (including IDH1 and RUNX1) was acquired at sAML transformation and was predominantly absent at sAML remission/relapsed PMF. Taken together, these findings illustrate the complex clonal dynamics associated with disease evolution in MPNs and sAML.

  3. The slowly pulsating B-star 18 Pegasi: A testbed for upper main sequence stellar evolution

    NASA Astrophysics Data System (ADS)

    Irrgang, A.; Desphande, A.; Moehler, S.; Mugrauer, M.; Janousch, D.

    2016-06-01

    The predicted width of the upper main sequence in stellar evolution models depends on the empirical calibration of the convective overshooting parameter. Despite decades of discussions, its precise value is still unknown and further observational constraints are required to gauge it. Based on a photometric and preliminary asteroseismic analysis, we show that the mid B-type giant 18 Peg is one of the most evolved members of the rare class of slowly pulsating B-stars and, thus, bears tremendous potential to derive a tight lower limit for the width of the upper main sequence. In addition, 18 Peg turns out to be part of a single-lined spectroscopic binary system with an eccentric orbit that is greater than 6 years. Further spectroscopic and photometric monitoring and a sophisticated asteroseismic investigation are required to exploit the full potential of this star as a benchmark object for stellar evolution theory. Based on observations collected at the European Organisation for Astronomical Research in the Southern Hemisphere under ESO programmes 265.C-5038(A), 069.C-0263(A), and 073.D-0024(A). Based on observations collected at the Centro Astronómico Hispano Alemán (CAHA) at Calar Alto, operated jointly by the Max-Planck Institut für Astronomie and the Instituto de Astrofísica de Andalucía (CSIC), proposals H2005-2.2-016 and H2015-3.5-008. Based on observations made with the William Herschel Telescope operated on the island of La Palma by the Isaac Newton Group in the Spanish Observatorio del Roque de los Muchachos of the Instituto de Astrofísica de Canarias, proposal W15BN015. Based on observations obtained with telescopes of the University Observatory Jena, which is operated by the Astrophysical Institute of the Friedrich-Schiller-University.

  4. Greater than the sum of its parts: single-nucleus sequencing identifies convergent evolution of independent EGFR mutants in GBM.

    PubMed

    Gini, Beatrice; Mischel, Paul S

    2014-08-01

    Single-cell sequencing approaches are needed to characterize the genomic diversity of complex tumors, shedding light on their evolutionary paths and potentially suggesting more effective therapies. In this issue of Cancer Discovery, Francis and colleagues develop a novel integrative approach to identify distinct tumor subpopulations based on joint detection of clonal and subclonal events from bulk tumor and single-nucleus whole-genome sequencing, allowing them to infer a subclonal architecture. Surprisingly, the authors identify convergent evolution of multiple, mutually exclusive, independent EGFR gain-of-function variants in a single tumor. This study demonstrates the value of integrative single-cell genomics and highlights the biologic primacy of EGFR as an actionable target in glioblastoma. ©2014 American Association for Cancer Research.

  5. Long sequence correlation coprocessor

    NASA Astrophysics Data System (ADS)

    Gage, Douglas W.

    1994-09-01

    A long sequence correlation coprocessor (LSCC) accelerates the bitwise correlation of arbitrarily long digital sequences by calculating in parallel the correlation score for 16, for example, adjacent bit alignments between two binary sequences. The LSCC integrated circuit is incorporated into a computer system with memory storage buffers and a separate general purpose computer processor which serves as its controller. Each of the LSCC's set of sequential counters simultaneously tallies a separate correlation coefficient. During each LSCC clock cycle, computer enable logic associated with each counter compares one bit of a first sequence with one bit of a second sequence to increment the counter if the bits are the same. A shift register assures that the same bit of the first sequence is simultaneously compared to different bits of the second sequence to simultaneously calculate the correlation coefficient by the different counters to represent different alignments of the two sequences.

  6. Next-Generation Sequencing Platforms

    NASA Astrophysics Data System (ADS)

    Mardis, Elaine R.

    2013-06-01

    Automated DNA sequencing instruments embody an elegant interplay among chemistry, engineering, software, and molecular biology and have built upon Sanger's founding discovery of dideoxynucleotide sequencing to perform once-unfathomable tasks. Combined with innovative physical mapping approaches that helped to establish long-range relationships between cloned stretches of genomic DNA, fluorescent DNA sequencers produced reference genome sequences for model organisms and for the reference human genome. New types of sequencing instruments that permit amazing acceleration of data-collection rates for DNA sequencing have been developed. The ability to generate genome-scale data sets is now transforming the nature of biological inquiry. Here, I provide an historical perspective of the field, focusing on the fundamental developments that predated the advent of next-generation sequencing instruments and providing information about how these instruments work, their application to biological research, and the newest types of sequencers that can extract data from single DNA molecules.

  7. Evolution of proteins.

    NASA Technical Reports Server (NTRS)

    Dayhoff, M. O.

    1971-01-01

    The amino acid sequences of proteins from living organisms are dealt with. The structure of proteins is first discussed; the variation in this structure from one biological group to another is illustrated by the first halves of the sequences of cytochrome c, and a phylogenetic tree is derived from the cytochrome c data. The relative geological times associated with the events of this tree are discussed. Errors which occur in the duplication of cells during the evolutionary process are examined. Particular attention is given to evolution of mutant proteins, globins, ferredoxin, and transfer ribonucleic acids (tRNA's). Finally, a general outline of biological evolution is presented.

  8. Cambro-ordovician sea-level fluctuations and sequence boundaries: The missing record and the evolution of new taxa

    USGS Publications Warehouse

    Lehnert, O.; Miller, J.F.; Leslie, Stephen A.; Repetski, J.E.; Ethington, Raymond L.

    2005-01-01

    The evolution of early Palaeozoic conodont faunas shows a clear connection to sea-level changes. One way that this connection manifests itself is that thick successions of carbonates are missing beneath major sequence boundaries due to karstification and erosion. From this observation arises the question of how many taxa have been lost from different conodont lineages in these incomplete successions. Although many taxa suffered extinction due to the environmental stresses associated with falling sea-levels, some must have survived in these extreme conditions. The number of taxa missing in the early Palaeozoic tropics always will be unclear, but it will be even more difficult to evaluate the missing record in detrital successions of higher latitudes. A common pattern in the evolution of Cambrian-Ordovician conodont lineages is appearances of new species at sea-level rises and disappearances at sea-level drops. This simple picture can be complicated by intervals that consistently have no representatives of a particular lineage, even after extensive sampling of the most complete sections. Presumably the lineages survived in undocumented refugia. In this paper, we give examples of evolution in Cambrian-Ordovician shallowmarine conodont faunas and highlight problems of undiscovered or truly missing segments of lineages. ?? The Palaeontological Association.

  9. Morphological change in machines accelerates the evolution of robust behavior

    PubMed Central

    Bongard, Josh

    2011-01-01

    Most animals exhibit significant neurological and morphological change throughout their lifetime. No robots to date, however, grow new morphological structure while behaving. This is due to technological limitations but also because it is unclear that morphological change provides a benefit to the acquisition of robust behavior in machines. Here I show that in evolving populations of simulated robots, if robots grow from anguilliform into legged robots during their lifetime in the early stages of evolution, and the anguilliform body plan is gradually lost during later stages of evolution, gaits are evolved for the final, legged form of the robot more rapidly—and the evolved gaits are more robust—compared to evolving populations of legged robots that do not transition through the anguilliform body plan. This suggests that morphological change, as well as the evolution of development, are two important processes that improve the automatic generation of robust behaviors for machines. It also provides an experimental platform for investigating the relationship between the evolution of development and robust behavior in biological organisms. PMID:21220304

  10. Evolutionary dynamics of Rh2 opsins in birds demonstrate an episode of accelerated evolution in the New World warblers (Setophaga)

    PubMed Central

    Price, Trevor D.

    2015-01-01

    Low rates of sequence evolution associated with purifying selection can be interrupted by episodic changes in selective regimes. Visual pigments are a unique system in which we can investigate the functional consequences of genetic changes, therefore connecting genotype to phenotype in the context of natural and sexual selection pressures. We study the RH2 and RH1 visual pigments (opsins) across 22 bird species belonging to two ecologically convergent clades, the New World warblers (Parulidae) and Old World warblers (Phylloscopidae), and evaluate rates of evolution in these clades along with data from 21 additional species. We demonstrate generally slow evolution of these opsins: both Rh1 and Rh2 are highly conserved across Old World and New World warblers. However, Rh2 underwent a burst of evolution within the New World genus Setophaga, where it accumulated substitutions at 6 amino acid sites across the species we studied. Evolutionary analyses revealed a significant increase in dN/dS in Setophaga, implying relatively strong selective pressures to overcome long-standing purifying selection. We studied the effects of each substitution on spectral tuning and found they do not cause large spectral shifts. Thus substitutions may reflect other aspects of opsin function, such as those affecting photosensitivity and/or dark-light adaptation. Although it is unclear what these alterations mean for color perception, we suggest that rapid evolution is linked to sexual selection, given the exceptional plumage colour diversification in Setophaga. PMID:25827331

  11. Geologic evolution and sequence stratigraphy of the offshore Pelotas Basin, southeast Brazil

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abreu, V.S.

    1996-01-01

    The Brazilian marginal basins have been studied since the beginning of the 70s. At least nine large basins are distributed along the entire Eastern continental margin. The sedimentary infill of these basins consists of lower Cretaceous (continental/lacustrine) rift section underlying marine upper Cretaceous (carbonate platforms) and marine upper Cretaceous/Tertiary sections, corresponding to the drift phase. The sedimentary deposits are a direct result of the Jurassic to lower Cretaceous break-up of the Pangea. This study will focus on the geologic evolution and sequence stratigraphic analysis of the Pelotas basin (offshore), located in the Southeast portion of the Brazilian continental margin betweenmore » 28[degrees] and 34[degrees] S, covering approximately 50,000 Km[sup 2]. During the early Cretaceous, when the break-up of the continent began in the south, thick basaltic layers were deposited in the Pelotas basin. These basalts form a thick and broad wedge of dipping seaward reflections interpreted as a transitional crust. During Albian to Turonian times, due to thermal subsidence, an extensive clastic/carbonate platform was developed, in an early drift stage. The sedimentation from the upper Cretaceous to Tertiary was characterized by a predominance of siliciclastics in the southeast margin, marking an accentuate deepening of the basin, showing several cycles related to eustatic fluctuations. Studies have addressed the problems of hydrocarbon exploration in deep water setting within a sequence stratigraphic framework. Thus Pelotas basin can provide a useful analogue for exploration efforts worldwide in offshore passive margins.« less

  12. Geologic evolution and sequence stratigraphy of the offshore Pelotas Basin, southeast Brazil

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Abreu, V.S.

    1996-12-31

    The Brazilian marginal basins have been studied since the beginning of the 70s. At least nine large basins are distributed along the entire Eastern continental margin. The sedimentary infill of these basins consists of lower Cretaceous (continental/lacustrine) rift section underlying marine upper Cretaceous (carbonate platforms) and marine upper Cretaceous/Tertiary sections, corresponding to the drift phase. The sedimentary deposits are a direct result of the Jurassic to lower Cretaceous break-up of the Pangea. This study will focus on the geologic evolution and sequence stratigraphic analysis of the Pelotas basin (offshore), located in the Southeast portion of the Brazilian continental margin betweenmore » 28{degrees} and 34{degrees} S, covering approximately 50,000 Km{sup 2}. During the early Cretaceous, when the break-up of the continent began in the south, thick basaltic layers were deposited in the Pelotas basin. These basalts form a thick and broad wedge of dipping seaward reflections interpreted as a transitional crust. During Albian to Turonian times, due to thermal subsidence, an extensive clastic/carbonate platform was developed, in an early drift stage. The sedimentation from the upper Cretaceous to Tertiary was characterized by a predominance of siliciclastics in the southeast margin, marking an accentuate deepening of the basin, showing several cycles related to eustatic fluctuations. Studies have addressed the problems of hydrocarbon exploration in deep water setting within a sequence stratigraphic framework. Thus Pelotas basin can provide a useful analogue for exploration efforts worldwide in offshore passive margins.« less

  13. Fully vectorial accelerating diffraction-free Helmholtz beams.

    PubMed

    Aleahmad, Parinaz; Miri, Mohammad-Ali; Mills, Matthew S; Kaminer, Ido; Segev, Mordechai; Christodoulides, Demetrios N

    2012-11-16

    We show that new families of diffraction-free nonparaxial accelerating optical beams can be generated by considering the symmetries of the underlying vectorial Helmholtz equation. Both two-dimensional transverse electric and magnetic accelerating wave fronts are possible, capable of moving along elliptic trajectories. Experimental results corroborate these predictions when these waves are launched from either the major or minor axis of the ellipse. In addition, three-dimensional spherical nondiffracting field configurations are presented along with their evolution dynamics. Finally, fully vectorial self-similar accelerating optical wave solutions are obtained via oblate-prolate spheroidal wave functions. In all occasions, these effects are illustrated via pertinent examples.

  14. Extrachromosomal oncogene amplification drives tumor evolution and genetic heterogeneity

    PubMed Central

    Turner, Kristen M.; Deshpande, Viraj; Beyter, Doruk; Koga, Tomoyuki; Rusert, Jessica; Lee, Catherine; Li, Bin; Arden, Karen; Ren, Bing; Nathanson, David A.; Kornblum, Harley I.; Taylor, Michael D.; Kaushal, Sharmeela; Cavenee, Webster K.; Wechsler-Reya, Robert; Furnari, Frank B.; Vandenberg, Scott R.; Rao, P. Nagesh; Wahl, Geoffrey M.; Bafna, Vineet; Mischel, Paul S.

    2017-01-01

    Human cells have twenty-three pairs of chromosomes but in cancer, genes can be amplified in chromosomes or in circular extrachromosomal DNA (ECDNA), whose frequency and functional significance are not understood1–4. We performed whole genome sequencing, structural modeling and cytogenetic analyses of 17 different cancer types, including 2572 metaphases, and developed ECdetect to conduct unbiased integrated ECDNA detection and analysis. ECDNA was found in nearly half of human cancers varying by tumor type, but almost never in normal cells. Driver oncogenes were amplified most commonly on ECDNA, elevating transcript level. Mathematical modeling predicted that ECDNA amplification elevates oncogene copy number and increases intratumoral heterogeneity more effectively than chromosomal amplification, which we validated by quantitative analyses of cancer samples. These results suggest that ECDNA contributes to accelerated evolution in cancer. PMID:28178237

  15. Dynamic evolution of Geranium mitochondrial genomes through multiple horizontal and intracellular gene transfers.

    PubMed

    Park, Seongjun; Grewe, Felix; Zhu, Andan; Ruhlman, Tracey A; Sabir, Jamal; Mower, Jeffrey P; Jansen, Robert K

    2015-10-01

    The exchange of genetic material between cellular organelles through intracellular gene transfer (IGT) or between species by horizontal gene transfer (HGT) has played an important role in plant mitochondrial genome evolution. The mitochondrial genomes of Geraniaceae display a number of unusual phenomena including highly accelerated rates of synonymous substitutions, extensive gene loss and reduction in RNA editing. Mitochondrial DNA sequences assembled for 17 species of Geranium revealed substantial reduction in gene and intron content relative to the ancestor of the Geranium lineage. Comparative analyses of nuclear transcriptome data suggest that a number of these sequences have been functionally relocated to the nucleus via IGT. Evidence for rampant HGT was detected in several Geranium species containing foreign organellar DNA from diverse eudicots, including many transfers from parasitic plants. One lineage has experienced multiple, independent HGT episodes, many of which occurred within the past 5.5 Myr. Both duplicative and recapture HGT were documented in Geranium lineages. The mitochondrial genome of Geranium brycei contains at least four independent HGT tracts that are absent in its nearest relative. Furthermore, G. brycei mitochondria carry two copies of the cox1 gene that differ in intron content, providing insight into contrasting hypotheses on cox1 intron evolution. © 2015 The Authors. New Phytologist © 2015 New Phytologist Trust.

  16. Focused Evolution of HIV-1 Neutralizing Antibodies Revealed by Structures and Deep Sequencing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wu, Xueling; Zhou, Tongqing; Zhu, Jiang

    2013-03-04

    Antibody VRC01 is a human immunoglobulin that neutralizes about 90% of HIV-1 isolates. To understand how such broadly neutralizing antibodies develop, we used x-ray crystallography and 454 pyrosequencing to characterize additional VRC01-like antibodies from HIV-1-infected individuals. Crystal structures revealed a convergent mode of binding for diverse antibodies to the same CD4-binding-site epitope. A functional genomics analysis of expressed heavy and light chains revealed common pathways of antibody-heavy chain maturation, confined to the IGHV1-2*02 lineage, involving dozens of somatic changes, and capable of pairing with different light chains. Broadly neutralizing HIV-1 immunity associated with VRC01-like antibodies thus involves the evolution ofmore » antibodies to a highly affinity-matured state required to recognize an invariant viral structure, with lineages defined from thousands of sequences providing a genetic roadmap of their development.« less

  17. Genomic fossils reveal adaptation of non-autonomous pararetroviruses driven by concerted evolution of noncoding regulatory sequences.

    PubMed

    Chen, Sunlu; Zheng, Huizhen; Kishima, Yuji

    2017-06-01

    The interplay of different virus species in a host cell after infection can affect the adaptation of each virus. Endogenous viral elements, such as endogenous pararetroviruses (PRVs), have arisen from vertical inheritance of viral sequences integrated into host germline genomes. As viral genomic fossils, these sequences can thus serve as valuable paleogenomic data to study the long-term evolutionary dynamics of virus-virus interactions, but they have rarely been applied for this purpose. All extant PRVs have been considered autonomous species in their parasitic life cycle in host cells. Here, we provide evidence for multiple non-autonomous PRV species with structural defects in viral activity that have frequently infected ancient grass hosts and adapted through interplay between viruses. Our paleogenomic analyses using endogenous PRVs in grass genomes revealed that these non-autonomous PRV species have participated in interplay with autonomous PRVs in a possible commensal partnership, or, alternatively, with one another in a possible mutualistic partnership. These partnerships, which have been established by the sharing of noncoding regulatory sequences (NRSs) in intergenic regions between two partner viruses, have been further maintained and altered by the sequence homogenization of NRSs between partners. Strikingly, we found that frequent region-specific recombination, rather than mutation selection, is the main causative mechanism of NRS homogenization. Our results, obtained from ancient DNA records of viruses, suggest that adaptation of PRVs has occurred by concerted evolution of NRSs between different virus species in the same host. Our findings further imply that evaluation of within-host NRS interactions within and between populations of viral pathogens may be important.

  18. ACCELERATION OF THERMAL PROTONS BY GENERIC PHENOMENOLOGICAL MECHANISMS

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Petrosian, Vahé; Kang, Byungwoo, E-mail: vahep@stanford.edu, E-mail: redcrux8@stanford.edu

    2015-11-01

    We investigate heating and acceleration of protons from a thermal gas with a generic diffusion and acceleration model, and subject to Coulomb scattering and energy loss, as was done by Petrosian and East for electrons. As protons gain energy their loss to electrons becomes important. Thus, we need to solve the coupled proton–electron kinetic equation. We numerically solve the coupled Fokker–Planck equations and compute the time evolution of the spectra of both particles. We show that this can lead to a quasi-thermal component plus a high-energy nonthermal tail. We determine the evolution of the nonthermal tail and the quasi-thermal component.more » The results may be used to explore the possibility of inverse bremsstrahlung radiation as a source of hard X-ray emissions from hot sources such as solar flares, accretion disk coronas, and the intracluster medium of galaxy clusters. We find that the emergence of nonthermal protons is accompanied by excessive heating of the entire plasma, unless the turbulence needed for scattering and acceleration is steeper than Kolmogorov and the acceleration parameters, the duration of the acceleration, and/or the initial distributions are significantly fine-tuned. These results severely constrain the feasibility of the nonthermal inverse bremsstrahlung process producing hard X-ray emissions. However, the nonthermal tail may be the seed particles for further re-acceleration to relativistic energies, say by a shock. In the Appendix we present some tests of the integrity of the algorithm used and present a new formula for the energy loss rate due to inelastic proton–proton interactions.« less

  19. Advances for Studying Clonal Evolution in Cancer

    PubMed Central

    Raphael, Benjamin J.; Chen, Feng; Wendl, Michael C.

    2013-01-01

    The “clonal evolution” model of cancer emerged and “evolved” amid ongoing advances in technology, especially in recent years during which next generation sequencing instruments have provided ever higher resolution pictures of the genetic changes in cancer cells and heterogeneity in tumors. It has become increasingly clear that clonal evolution is not a single sequential process, but instead frequently involves simultaneous evolution of multiple subclones that co-exist because they are of similar fitness or are spatially separated. Co-evolution of subclones also occurs when they complement each other’s survival advantages. Recent studies have also shown that clonal evolution is highly heterogeneous: different individual tumors of the same type may undergo very different paths of clonal evolution. New methodological advancements, including deep digital sequencing of a mixed tumor population, single cell sequencing, and the development of more sophisticated computational tools, will continue to shape and reshape the models of clonal evolution. In turn, these will provide both an improved framework for the understanding of cancer progression and a guide for treatment strategies aimed at the elimination of all, rather than just some, of the cancer cells within a patient. PMID:23353056

  20. Molecular Evolution in Historical Perspective.

    PubMed

    Suárez-Díaz, Edna

    2016-12-01

    In the 1960s, advances in protein chemistry and molecular genetics provided new means for the study of biological evolution. Amino acid sequencing, nucleic acid hybridization, zone gel electrophoresis, and immunochemistry were some of the experimental techniques that brought about new perspectives to the study of the patterns and mechanisms of evolution. New concepts, such as the molecular evolutionary clock, and the discovery of unexpected molecular phenomena, like the presence of repetitive sequences in eukaryotic genomes, eventually led to the realization that evolution might occur at a different pace at the organismic and the molecular levels, and according to different mechanisms. These developments sparked important debates between defendants of the molecular and organismic approaches. The most vocal confrontations focused on the relation between primates and humans, and the neutral theory of molecular evolution. By the 1980s and 1990s, the construction of large protein and DNA sequences databases, and the development of computer-based statistical tools, facilitated the coming together of molecular and evolutionary biology. Although in its contemporary form the field of molecular evolution can be traced back to the last five decades, the field has deep roots in twentieth century experimental life sciences. For historians of science, the origins and consolidation of molecular evolution provide a privileged field for the study of scientific debates, the relation between technological advances and scientific knowledge, and the connection between science and broader social concerns.

  1. Lithium in halo stars from standard stellar evolution

    NASA Technical Reports Server (NTRS)

    Deliyannis, Constantine P.; Demarque, Pierre; Kawaler, Steven D.

    1990-01-01

    A grid has been constructed of theoretical evolution sequences of models for low-metallicity stars from the premain-sequence to the giant branch phases. The grid is used to study the history of surface Li abundance during standard stellar evolution. The Li-7 observations of halo stars by Spite and Spite (1982) and subsequent observations are synthesized to separate the halo stars by age. The theory of surface Li abundance is illustrated by following the evolution of a reference halo star model from the contracting fully convective premain sequence to the giant branch phase. The theoretical models are compared with observed Li abundances. The results show that the halo star lithium abundances can be explained in the context of standard stellar evolution theory using completely standard assumptions and physics.

  2. Pressure fluctuation caused by moderate acceleration

    NASA Astrophysics Data System (ADS)

    Tagawa, Yoshiyuki; Kurihara, Chihiro; Kiyama, Akihito

    2017-11-01

    Pressure fluctuation caused by acceleration of a liquid column is observed in various important technologies, e.g. water-hammer in a pipeline. The magnitude of fluctuation can be estimated by two different approaches: When the duration time of acceleration is much shorter than the propagation time for a pressure wave to travel the length of the liquid column, e.g. sudden valve closure for a long pipe, Joukowsky equation is applied. In contrast, if the acceleration duration is much longer, the liquid is modeled as a rigid column, ignoring compressibility of the fluid. However, many of practical cases exist between these two extremes. In this study we propose a model describing pressure fluctuation when the duration of acceleration is in the same order of the propagation time for a pressure wave, i.e. under moderate acceleration. The novel model considers both temporal and spatial evolutions of pressure propagation as well as gradual pressure rise during the acceleration. We conduct experiments in which we impose acceleration to a liquid with varying the length of the liquid column, acceleration duration, and properties of liquids. The ratio between the acceleration duration and the propagation time is in the range of 0.02 - 2. The model agrees well with measurement results. JSPS KAKENHI Grant Numbers 26709007 and 17H01246.

  3. The identification of complete domains within protein sequences using accurate E-values for semi-global alignment

    PubMed Central

    Kann, Maricel G.; Sheetlin, Sergey L.; Park, Yonil; Bryant, Stephen H.; Spouge, John L.

    2007-01-01

    The sequencing of complete genomes has created a pressing need for automated annotation of gene function. Because domains are the basic units of protein function and evolution, a gene can be annotated from a domain database by aligning domains to the corresponding protein sequence. Ideally, complete domains are aligned to protein subsequences, in a ‘semi-global alignment’. Local alignment, which aligns pieces of domains to subsequences, is common in high-throughput annotation applications, however. It is a mature technique, with the heuristics and accurate E-values required for screening large databases and evaluating the screening results. Hidden Markov models (HMMs) provide an alternative theoretical framework for semi-global alignment, but their use is limited because they lack heuristic acceleration and accurate E-values. Our new tool, GLOBAL, overcomes some limitations of previous semi-global HMMs: it has accurate E-values and the possibility of the heuristic acceleration required for high-throughput applications. Moreover, according to a standard of truth based on protein structure, two semi-global HMM alignment tools (GLOBAL and HMMer) had comparable performance in identifying complete domains, but distinctly outperformed two tools based on local alignment. When searching for complete protein domains, therefore, GLOBAL avoids disadvantages commonly associated with HMMs, yet maintains their superior retrieval performance. PMID:17596268

  4. Gauss-Bonnet cosmology unifying late and early-time acceleration eras with intermediate eras

    NASA Astrophysics Data System (ADS)

    Oikonomou, V. K.

    2016-07-01

    In this paper we demonstrate that with vacuum F(G) gravity it is possible to describe the unification of late and early-time acceleration eras with the radiation and matter domination era. The Hubble rate of the unified evolution contains two mild singularities, so called Type IV singularities, and the evolution itself has some appealing features, such as the existence of a deceleration-acceleration transition at late times. We also address quantitatively a fundamental question related to modified gravity models description of cosmological evolution: Is it possible for all modified gravity descriptions of our Universe evolution, to produce a nearly scale invariant spectrum of primordial curvature perturbations? As we demonstrate, the answer for the F(G) description is no, since the resulting power spectrum is not scale invariant, in contrast to the F(R) description studied in the literature. Therefore, although the cosmological evolution can be realized in the context of vacuum F(G) gravity, the evolution is not compatible with the observational data, in contrast to the F(R) gravity description of the same cosmological evolution.

  5. Evolution of epigenetic regulation in vertebrate genomes

    PubMed Central

    Lowdon, Rebecca F.; Jang, Hyo Sik; Wang, Ting

    2016-01-01

    Empirical models of sequence evolution have spurred progress in the field of evolutionary genetics for decades. We are now realizing the importance and complexity of the eukaryotic epigenome. While epigenome analysis has been applied to genomes from single cell eukaryotes to human, comparative analyses are still relatively few, and computational algorithms to quantify epigenome evolution remain scarce. Accordingly, a quantitative model of epigenome evolution remains to be established. Here we review the comparative epigenomics literature and synthesize its overarching themes. We also suggest one mechanism, transcription factor binding site turnover, which relates sequence evolution to epigenetic conservation or divergence. Lastly, we propose a framework for how the field can move forward to build a coherent quantitative model of epigenome evolution. PMID:27080453

  6. Comparative analyses of two Geraniaceae transcriptomes using next-generation sequencing.

    PubMed

    Zhang, Jin; Ruhlman, Tracey A; Mower, Jeffrey P; Jansen, Robert K

    2013-12-29

    Organelle genomes of Geraniaceae exhibit several unusual evolutionary phenomena compared to other angiosperm families including accelerated nucleotide substitution rates, widespread gene loss, reduced RNA editing, and extensive genomic rearrangements. Since most organelle-encoded proteins function in multi-subunit complexes that also contain nuclear-encoded proteins, it is likely that the atypical organellar phenomena affect the evolution of nuclear genes encoding organellar proteins. To begin to unravel the complex co-evolutionary interplay between organellar and nuclear genomes in this family, we sequenced nuclear transcriptomes of two species, Geranium maderense and Pelargonium x hortorum. Normalized cDNA libraries of G. maderense and P. x hortorum were used for transcriptome sequencing. Five assemblers (MIRA, Newbler, SOAPdenovo, SOAPdenovo-trans [SOAPtrans], Trinity) and two next-generation technologies (454 and Illumina) were compared to determine the optimal transcriptome sequencing approach. Trinity provided the highest quality assembly of Illumina data with the deepest transcriptome coverage. An analysis to determine the amount of sequencing needed for de novo assembly revealed diminishing returns of coverage and quality with data sets larger than sixty million Illumina paired end reads for both species. The G. maderense and P. x hortorum transcriptomes contained fewer transcripts encoding the PLS subclass of PPR proteins relative to other angiosperms, consistent with reduced mitochondrial RNA editing activity in Geraniaceae. In addition, transcripts for all six plastid targeted sigma factors were identified in both transcriptomes, suggesting that one of the highly divergent rpoA-like ORFs in the P. x hortorum plastid genome is functional. The findings support the use of the Illumina platform and assemblers optimized for transcriptome assembly, such as Trinity or SOAPtrans, to generate high-quality de novo transcriptomes with broad coverage. In addition

  7. Field Monitoring of Avian Influenza Viruses: Whole-Genome Sequencing and Tracking of Neuraminidase Evolution Using 454 Pyrosequencing

    PubMed Central

    Croville, Guillaume; Soubies, Sébastien Mathieu; Barbieri, Johanna; Klopp, Christophe; Mariette, Jérôme; Bouchez, Olivier; Camus-Bouclainville, Christelle

    2012-01-01

    Adaptation of avian influenza viruses (AIVs) from waterfowl to domestic poultry with a deletion in the neuraminidase (NA) stalk has already been reported. The way the virus undergoes this evolution, however, is thus far unclear. We address this question using pyrosequencing of duck and turkey low-pathogenicity AIVs. Ducks and turkeys were sampled at the very beginning of an H6N1 outbreak, and turkeys were swabbed again 8 days later. NA stalk deletions were evidenced in turkeys by Sanger sequencing. To further investigate viral evolution, 454 pyrosequencing was performed: for each set of samples, up to 41,500 reads of ca. 400 bp were generated and aligned. Genetic polymorphisms between duck and turkey viruses were tracked on the whole genome. NA deletion was detected in less than 2% of reads in duck feces but in 100% of reads in turkey tracheal specimens collected at the same time. Further variations in length were observed in NA from turkeys 8 days later. Similarly, minority mutants emerged on the hemagglutinin (HA) gene, with substitutions mostly in the receptor binding site on the globular head. These critical changes suggest a strong evolutionary pressure in turkeys. The increasing performances of next-generation sequencing technologies should enable us to monitor the genomic diversity of avian influenza viruses and early emergence of potentially pathogenic variants within bird flocks. The present study, based on 454 pyrosequencing, suggests that NA deletion, an example of AIV adaptation from waterfowl to domestic poultry, occurs by selection rather than de novo emergence of viral mutants. PMID:22718944

  8. The Molecular Clock of Neutral Evolution Can Be Accelerated or Slowed by Asymmetric Spatial Structure

    PubMed Central

    Allen, Benjamin; Sample, Christine; Dementieva, Yulia; Medeiros, Ruben C.; Paoletti, Christopher; Nowak, Martin A.

    2015-01-01

    Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, K, at which these substitutions accumulate in the population coincides with the mutation rate, u, at which they arise in individuals: K = u. This identity enables genetic sequence data to be used as a “molecular clock” to estimate the timing of evolutionary events. While the molecular clock is known to be perturbed by selection, it is thought that K = u holds very generally for neutral evolution. Here we show that asymmetric spatial population structure can alter the molecular clock rate for neutral mutations, leading to either Ku. Our results apply to a general class of haploid, asexually reproducing, spatially structured populations. Deviations from K = u occur because mutations arise unequally at different sites and have different probabilities of fixation depending on where they arise. If birth rates are uniform across sites, then K ≤ u. In general, K can take any value between 0 and Nu. Our model can be applied to a variety of population structures. In one example, we investigate the accumulation of genetic mutations in the small intestine. In another application, we analyze over 900 Twitter networks to study the effect of network topology on the fixation of neutral innovations in social evolution. PMID:25719560

  9. The molecular clock of neutral evolution can be accelerated or slowed by asymmetric spatial structure.

    PubMed

    Allen, Benjamin; Sample, Christine; Dementieva, Yulia; Medeiros, Ruben C; Paoletti, Christopher; Nowak, Martin A

    2015-02-01

    Over time, a population acquires neutral genetic substitutions as a consequence of random drift. A famous result in population genetics asserts that the rate, K, at which these substitutions accumulate in the population coincides with the mutation rate, u, at which they arise in individuals: K = u. This identity enables genetic sequence data to be used as a "molecular clock" to estimate the timing of evolutionary events. While the molecular clock is known to be perturbed by selection, it is thought that K = u holds very generally for neutral evolution. Here we show that asymmetric spatial population structure can alter the molecular clock rate for neutral mutations, leading to either Ku. Our results apply to a general class of haploid, asexually reproducing, spatially structured populations. Deviations from K = u occur because mutations arise unequally at different sites and have different probabilities of fixation depending on where they arise. If birth rates are uniform across sites, then K ≤ u. In general, K can take any value between 0 and Nu. Our model can be applied to a variety of population structures. In one example, we investigate the accumulation of genetic mutations in the small intestine. In another application, we analyze over 900 Twitter networks to study the effect of network topology on the fixation of neutral innovations in social evolution.

  10. Acceleration of Relativistic Electrons: A Comparison of Two Models

    NASA Astrophysics Data System (ADS)

    Green, J. C.; Kivelson, M. G.

    2001-12-01

    Observations of relativistic electron fluxes show order of magnitude increases during some geomagnetic storms. Many electron acceleration models have been proposed to explain the flux enhancements but attempts to validate these models have yielded ambiguous results. Here we examine two models of electron acceleration, radial diffusion via enhanced ULF wave activity [Elkington et al.,1999] and acceleration by resonant interaction with whistler waves[Summers,1998; Roth et al.,1999]. Two methods are used to compare observations with features predicted by the models. First, the evolution of phase space density as a function of L during flux enhancement events is evaluated. The phase space density (PSD) is calculated at constant first, second and third adiabatic invariants using data obtained by the CEPPAD-HIST instrument and the MFE instrument onboard the Polar spacecraft. Liouville's theorem states that PSD calculated at constant adiabatic invariants does not change with time unless some mechanism violates one of the invariants. The radial diffusion model predicts that only the flux invariant will be violated during the acceleration process while acceleration by whistler waves violates the first invariant. Therefore, the two models predict a different evolution of the PSD as a function of time and L. Previous examinations of the evolution of PSD have yielded ambiguous results because PSD calculations are highly dependent on the global accuracy of magnetic field models. We examine the PSD versus L profiles for a series of geomagnetic storms and in addition determine how errors in the Tsyganenko 96 field model affect the results by comparing the measured magnetic field to the model magnetic field used in the calculations. Second, the evolution of the relativistic electron pitch angle distributions is evaluated. Previous studies of pitch angle distributions were limited because few spacecraft have the necessary instrumentation and global coverage. The CEPPAD

  11. Development of a State Machine Sequencer for the Keck Interferometer: Evolution, Development and Lessons Learned using a CASE Tool Approach

    NASA Technical Reports Server (NTRS)

    Rede, Leonard J.; Booth, Andrew; Hsieh, Jonathon; Summer, Kellee

    2004-01-01

    This paper presents a discussion of the evolution of a sequencer from a simple EPICS (Experimental Physics and Industrial Control System) based sequencer into a complex implementation designed utilizing UML (Unified Modeling Language) methodologies and a CASE (Computer Aided Software Engineering) tool approach. The main purpose of the sequencer (called the IF Sequencer) is to provide overall control of the Keck Interferometer to enable science operations be carried out by a single operator (and/or observer). The interferometer links the two 10m telescopes of the W. M. Keck Observatory at Mauna Kea, Hawaii. The IF Sequencer is a high-level, multi-threaded, Hare1 finite state machine, software program designed to orchestrate several lower-level hardware and software hard real time subsystems that must perform their work in a specific and sequential order. The sequencing need not be done in hard real-time. Each state machine thread commands either a high-speed real-time multiple mode embedded controller via CORB A, or slower controllers via EPICS Channel Access interfaces. The overall operation of the system is simplified by the automation. The UML is discussed and our use of it to implement the sequencer is presented. The decision to use the Rhapsody product as our CASE tool is explained and reflected upon. Most importantly, a section on lessons learned is presented and the difficulty of integrating CASE tool automatically generated C++ code into a large control system consisting of multiple infrastructures is presented.

  12. Development of a state machine sequencer for the Keck Interferometer: evolution, development, and lessons learned using a CASE tool approach

    NASA Astrophysics Data System (ADS)

    Reder, Leonard J.; Booth, Andrew; Hsieh, Jonathan; Summers, Kellee R.

    2004-09-01

    This paper presents a discussion of the evolution of a sequencer from a simple Experimental Physics and Industrial Control System (EPICS) based sequencer into a complex implementation designed utilizing UML (Unified Modeling Language) methodologies and a Computer Aided Software Engineering (CASE) tool approach. The main purpose of the Interferometer Sequencer (called the IF Sequencer) is to provide overall control of the Keck Interferometer to enable science operations to be carried out by a single operator (and/or observer). The interferometer links the two 10m telescopes of the W. M. Keck Observatory at Mauna Kea, Hawaii. The IF Sequencer is a high-level, multi-threaded, Harel finite state machine software program designed to orchestrate several lower-level hardware and software hard real-time subsystems that must perform their work in a specific and sequential order. The sequencing need not be done in hard real-time. Each state machine thread commands either a high-speed real-time multiple mode embedded controller via CORBA, or slower controllers via EPICS Channel Access interfaces. The overall operation of the system is simplified by the automation. The UML is discussed and our use of it to implement the sequencer is presented. The decision to use the Rhapsody product as our CASE tool is explained and reflected upon. Most importantly, a section on lessons learned is presented and the difficulty of integrating CASE tool automatically generated C++ code into a large control system consisting of multiple infrastructures is presented.

  13. Using MELTS to understand the evolution of silicic magmas: Challenges and successes in modeling the Highland Range Volcanic Sequence (NV)

    NASA Astrophysics Data System (ADS)

    Vaum, R. C.; Gualda, G. A.; Ghiorso, M. S.; Miller, C. F.; Colombini, L. L.

    2009-12-01

    The Highland Range near Searchlight, Nevada is comprised of mid-Miocene, intermediate to silicic volcanic rocks. This study focuses on the most silicic portion of the eruptive sequence (16.0-16.5 Ma). The first eruptions during this interval were effusive and produced trachydacite (66-70 wt% SiO2), but later the eruptive style shifted to explosive and compositions were more evolved (70-78 wt% SiO2). Glass compositions in rocks saturated in both quartz and sanidine align along the 150 MPa quartz+sanidine saturation surface, suggesting that the Highland Range magmas equilibrated in a single reservoir at that pressure. We are interested in better understanding this transition in eruptive style from effusive to eruptive, and our approach is based on modeling melt evolution using MELTS thermodynamic modeling software. We selected representative samples from key stratigraphic units, and focused on samples for which whole-rock and glass compositions, as well as mineral abundances, are available. This allows for direct comparison of simulation results with existing data. Initial simulations showed that MELTS predicts unrealistic paths of evolution when compared to the glass compositions and to the phase relations in the Qz-Ab-Or ternary. In particular, the stability field of quartz predicted by MELTS is much too small, causing melts to become exceedingly silicic (>80 wt% SiO2). Sanidine, on the other hand, has fairly sodic compositions and crystallizes too early in the sequence; therefore, simulated melt compositions are never as potassic as the analyzed glasses. Similar results are obtained when modeling the evolution of the Bishop and Campanian magmas, showing that these are systematic problems in MELTS calibration. Accordingly, we have adjusted the enthalpy of quartz and potassium end-member of the feldspar solid solution in MELTS so that the quartz-sanidine saturation surface is correctly predicted. We find that this modified version of MELTS much better models the

  14. From inflation to recent cosmic acceleration: the fermionic Elko field driving the evolution of the universe

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pereira, S.H.; Guimarães, T.M., E-mail: shpereira@feg.unesp.br, E-mail: thiago.mogui@gmail.com

    In this paper we construct the complete evolution of the universe driven by the mass dimension one dark spinor called Elko, starting with inflation, passing by the matter dominated era and finishing with the recent accelerated expansion. The dynamic of the fermionic Elko field with a symmetry breaking type potential can reproduce all phases of the universe in a natural and elegant way. The dynamical equations in general case and slow roll conditions in the limit H || m {sub pl} are also presented for the Elko system. Numerical analysis for the number of e-foldings during inflation, energy density aftermore » inflation and for present time and also the actual size of the universe are in good agreement with the standard model of cosmology. An interpretation of the inflationary phase as a result of Pauli exclusion principle is also possible if the Elko field is treated as an average value of its quantum analogue.« less

  15. Full-Length Venom Protein cDNA Sequences from Venom-Derived mRNA: Exploring Compositional Variation and Adaptive Multigene Evolution

    PubMed Central

    Modahl, Cassandra M.; Mackessy, Stephen P.

    2016-01-01

    access to cDNA sequences in the absence of living specimens, even from commercial venom sources, to evaluate important regional differences in venom composition and to study snake venom protein evolution. PMID:27280639

  16. Whole-genome sequence of the Tibetan frog Nanorana parkeri and the comparative evolution of tetrapod genomes.

    PubMed

    Sun, Yan-Bo; Xiong, Zi-Jun; Xiang, Xue-Yan; Liu, Shi-Ping; Zhou, Wei-Wei; Tu, Xiao-Long; Zhong, Li; Wang, Lu; Wu, Dong-Dong; Zhang, Bao-Lin; Zhu, Chun-Ling; Yang, Min-Min; Chen, Hong-Man; Li, Fang; Zhou, Long; Feng, Shao-Hong; Huang, Chao; Zhang, Guo-Jie; Irwin, David; Hillis, David M; Murphy, Robert W; Yang, Huan-Ming; Che, Jing; Wang, Jun; Zhang, Ya-Ping

    2015-03-17

    The development of efficient sequencing techniques has resulted in large numbers of genomes being available for evolutionary studies. However, only one genome is available for all amphibians, that of Xenopus tropicalis, which is distantly related from the majority of frogs. More than 96% of frogs belong to the Neobatrachia, and no genome exists for this group. This dearth of amphibian genomes greatly restricts genomic studies of amphibians and, more generally, our understanding of tetrapod genome evolution. To fill this gap, we provide the de novo genome of a Tibetan Plateau frog, Nanorana parkeri, and compare it to that of X. tropicalis and other vertebrates. This genome encodes more than 20,000 protein-coding genes, a number similar to that of Xenopus. Although the genome size of Nanorana is considerably larger than that of Xenopus (2.3 vs. 1.5 Gb), most of the difference is due to the respective number of transposable elements in the two genomes. The two frogs exhibit considerable conserved whole-genome synteny despite having diverged approximately 266 Ma, indicating a slow rate of DNA structural evolution in anurans. Multigenome synteny blocks further show that amphibians have fewer interchromosomal rearrangements than mammals but have a comparable rate of intrachromosomal rearrangements. Our analysis also identifies 11 Mb of anuran-specific highly conserved elements that will be useful for comparative genomic analyses of frogs. The Nanorana genome offers an improved understanding of evolution of tetrapod genomes and also provides a genomic reference for other evolutionary studies.

  17. PROBING DYNAMICS OF ELECTRON ACCELERATION WITH RADIO AND X-RAY SPECTROSCOPY, IMAGING, AND TIMING IN THE 2002 APRIL 11 SOLAR FLARE

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Fleishman, Gregory D.; Nita, Gelu M.; Gary, Dale E.

    Based on detailed analysis of radio and X-ray observations of a flare on 2002 April 11 augmented by realistic three-dimensional modeling, we have identified a radio emission component produced directly at the flare acceleration region. This acceleration region radio component has distinctly different (1) spectrum, (2) light curves, (3) spatial location, and, thus, (4) physical parameters from those of the separately identified trapped or precipitating electron components. To derive evolution of physical parameters of the radio sources we apply forward fitting of the radio spectrum time sequence with the gyrosynchrotron source function with five to six free parameters. At themore » stage when the contribution from the acceleration region dominates the radio spectrum, the X-ray- and radio-derived electron energy spectral indices agree well with each other. During this time the maximum energy of the accelerated electron spectrum displays a monotonic increase with time from {approx}300 keV to {approx}2 MeV over roughly one minute duration indicative of an acceleration process in the form of growth of the power-law tail; the fast electron residence time in the acceleration region is about 2-4 s, which is much longer than the time of flight and so requires a strong diffusion mode there to inhibit free-streaming propagation. The acceleration region has a relatively strong magnetic field, B {approx} 120 G, and a low thermal density, n{sub e} {approx}< 2 Multiplication-Sign 10{sup 9} cm{sup -3}. These acceleration region properties are consistent with a stochastic acceleration mechanism.« less

  18. Did A Planet Survive A Post-Main Sequence Evolutionary Event?

    NASA Astrophysics Data System (ADS)

    Sorber, Rebecca; Jang-Condell, Hannah; Zimmerman, Mara

    2018-06-01

    The GL86 is star system approximately 10 pc away with a main sequence K- type ~ 0.77 M⊙ star (GL 86A) with a white dwarf ~0.49 M⊙ companion (GL86 B). The system has a ~ 18.4 AU semi-major axis, an orbital period of ~353 yrs, and an eccentricity of ~ 0.39. A 4.5 MJ planet orbits the main sequence star with a semi-major axis of 0.113 AU, an orbital period of 15.76 days, in a near circular orbit with an eccentricity of 0.046. If we assume that this planet was formed during the time when the white dwarf was a main sequence star, it would be difficult for the planet to have remained in a stable orbit during the post-main sequence evolution of GL86 B. The post-main sequence evolution with planet survival will be examined by modeling using the program Mercury (Chambers 1999). Using the model, we examine the origins of the planet: whether it formed before or after the post-main sequence evolution of GL86B. The modeling will give us insight into the dynamical evolution of, not only, the binary star system, but also the planet’s life cycle.

  19. Liver acquisition with acceleration volume acquisition gadolinium-enhanced magnetic resonance combined with T2 sequences in the diagnosis of local recurrence of rectal cancer.

    PubMed

    Cao, Wuteng; Li, Fangqian; Gong, Jiaying; Liu, Dechao; Deng, Yanhong; Kang, Liang; Zhou, Zhiyang

    2016-11-22

    To investigate the efficacy of liver acquisition with acceleration volume acquisition (LAVA) gadolinium-enhanced magnetic resonance (MR) sequences and to assess its added accuracy in diagnosing local recurrence (LR) of rectal cancer with conventional T2-weighted fast spin echo (FSE) sequences. Pelvic MRI, including T2-weighted FSE sequences, gadolinium-enhanced sequences of LAVA and T1-weighted FSE with fat suppression, was performed on 225 patients with postoperative rectal cancer. Two readers evaluated the presence of LR according to "T2" (T2 sequences only), "T2 + LAVA-Gad" (LAVA and T2 imaging), and "T2 + T1-fs-Gad" (T1 fat suppression-enhanced sequence with T2 images). To evaluate diagnostic efficiency, imaging quality with LAVA and T1-fs-Gad by subjective scores and the signal intensity (SI) ratio. In the result, the SI ratio of LAVA was significantly higher than that of T1-fs-Gad (p = 0.0001). The diagnostic efficiency of "T2 + LAVA-Gad" was better than that of "T2 + T1-fs-Gad" (p = 0.0016 for Reader 1, p = 0.0001 for Reader 2) and T2 imaging only (p = 0.0001 for Reader 1; p = 0.0001 for Reader 2). Therefore, LAVA gadolinium-enhanced MR increases the accuracy of diagnosis of LR from rectal cancer and could replace conventional T1 gadolinium-enhanced sequences in the postoperative pelvic follow-up of rectal cancer.

  20. Whole-genome de novo sequencing reveals unique genes that contributed to the adaptive evolution of the Mikado pheasant.

    PubMed

    Lee, Chien-Yueh; Hsieh, Ping-Han; Chiang, Li-Mei; Chattopadhyay, Amrita; Li, Kuan-Yi; Lee, Yi-Fang; Lu, Tzu-Pin; Lai, Liang-Chuan; Lin, En-Chung; Lee, Hsinyu; Ding, Shih-Torng; Tsai, Mong-Hsun; Chen, Chien-Yu; Chuang, Eric Y

    2018-05-01

    The Mikado pheasant (Syrmaticus mikado) is a nearly endangered species indigenous to high-altitude regions of Taiwan. This pheasant provides an opportunity to investigate evolutionary processes following geographic isolation. Currently, the genetic background and adaptive evolution of the Mikado pheasant remain unclear. We present the draft genome of the Mikado pheasant, which consists of 1.04 Gb of DNA and 15,972 annotated protein-coding genes. The Mikado pheasant displays expansion and positive selection of genes related to features that contribute to its adaptive evolution, such as energy metabolism, oxygen transport, hemoglobin binding, radiation response, immune response, and DNA repair. To investigate the molecular evolution of the major histocompatibility complex (MHC) across several avian species, 39 putative genes spanning 227 kb on a contiguous region were annotated and manually curated. The MHC loci of the pheasant revealed a high level of synteny, several rapidly evolving genes, and inverse regions compared to the same loci in the chicken. The complete mitochondrial genome was also sequenced, assembled, and compared against four long-tailed pheasants. The results from molecular clock analysis suggest that ancestors of the Mikado pheasant migrated from the north to Taiwan about 3.47 million years ago. This study provides a valuable genomic resource for the Mikado pheasant, insights into its adaptation to high altitude, and the evolutionary history of the genus Syrmaticus, which could potentially be useful for future studies that investigate molecular evolution, genomics, ecology, and immunogenetics.

  1. A stacked Late Quaternary fluvio-periglacial sequence from the Axe valley, southern England with implications for landscape evolution and Palaeolithic archaeology

    NASA Astrophysics Data System (ADS)

    Brown, A. G.; Basell, L. S.; Toms, P. S.

    2015-05-01

    caused pulsed aggradation until the last termination. It is also proposed that interglacial and interstadial incision may have been prevented by the over-sized and interlocking nature of the sub-angular chert clasts until the Lateglacial when confinement of the river overcame this immobility threshold. One result of this hydrogeologically mediated valley evolution was to provide a sequence of proximal Palaeolithic archaeology over two MIS cycles. This study demonstrates that uplift tectonics and climate alone do not fully determine Quaternary valley evolution and that lithological and hydrogeological conditions are a fundamental cause of variation in terrestrial Quaternary records and landform evolution.

  2. Tropics accelerate the evolution of hybrid male sterility in Drosophila.

    PubMed

    Yukilevich, Roman

    2013-06-01

    Understanding the evolutionary mechanisms that facilitate speciation and explain global patterns of species diversity has remained a challenge for decades. The most general pattern of species biodiversity is the latitudinal gradient, whereby species richness increases toward the tropics. Although such a global pattern probably has a multitude of causes, recent attention has focused on the hypothesis that speciation and the evolution of reproductive isolation occur faster in the tropics. Here, I tested this prediction using a dataset on premating and postzygotic isolation between recently diverged Drosophila species. Results showed that while the evolution of premating isolation was not greater between tropical Drosophila relative to nontropical species, postzygotic isolation evolved faster in the tropics. In particular, hybrid male sterility was much greater among tropical Drosophila compared to nontropical species pairs of similar genetic age. Several testable explanations for the novel pattern are discussed, including greater role for sterility-inducing bacterial endosymbionts in the tropics and more intense sperm-sperm competition or sperm-egg sexual conflict in the tropics. The results imply that processes of speciation in the tropics may evolve at different rates or may even be somewhat different from those at higher latitudes. © 2013 The Author(s). Evolution © 2013 The Society for the Study of Evolution.

  3. Co-evolution of SNF spliceosomal proteins with their RNA targets in trans-splicing nematodes.

    PubMed

    Strange, Rex Meade; Russelburg, L Peyton; Delaney, Kimberly J

    2016-08-01

    Although the mechanism of pre-mRNA splicing has been well characterized, the evolution of spliceosomal proteins is poorly understood. The U1A/U2B″/SNF family (hereafter referred to as the SNF family) of RNA binding spliceosomal proteins participates in both the U1 and U2 small interacting nuclear ribonucleoproteins (snRNPs). The highly constrained nature of this system has inhibited an analysis of co-evolutionary trends between the proteins and their RNA binding targets. Here we report accelerated sequence evolution in the SNF protein family in Phylum Nematoda, which has allowed an analysis of protein:RNA co-evolution. In a comparison of SNF genes from ecdysozoan species, we found a correlation between trans-splicing species (nematodes) and increased phylogenetic branch lengths of the SNF protein family, with respect to their sister clade Arthropoda. In particular, we found that nematodes (~70-80 % of pre-mRNAs are trans-spliced) have experienced higher rates of SNF sequence evolution than arthropods (predominantly cis-spliced) at both the nucleotide and amino acid levels. Interestingly, this increased evolutionary rate correlates with the reliance on trans-splicing by nematodes, which would alter the role of the SNF family of spliceosomal proteins. We mapped amino acid substitutions to functionally important regions of the SNF protein, specifically to sites that are predicted to disrupt protein:RNA and protein:protein interactions. Finally, we investigated SNF's RNA targets: the U1 and U2 snRNAs. Both are more divergent in nematodes than arthropods, suggesting the RNAs have co-evolved with SNF in order to maintain the necessarily high affinity interaction that has been characterized in other species.

  4. Genome-wide signatures of convergent evolution in echolocating mammals

    PubMed Central

    Parker, Joe; Tsagkogeorga, Georgia; Cotton, James A.; Liu, Yuan; Provero, Paolo; Stupka, Elia; Rossiter, Stephen J.

    2013-01-01

    Evolution is typically thought to proceed through divergence of genes, proteins, and ultimately phenotypes1-3. However, similar traits might also evolve convergently in unrelated taxa due to similar selection pressures4,5. Adaptive phenotypic convergence is widespread in nature, and recent results from a handful of genes have suggested that this phenomenon is powerful enough to also drive recurrent evolution at the sequence level6-9. Where homoplasious substitutions do occur these have long been considered the result of neutral processes. However, recent studies have demonstrated that adaptive convergent sequence evolution can be detected in vertebrates using statistical methods that model parallel evolution9,10 although the extent to which sequence convergence between genera occurs across genomes is unknown. Here we analyse genomic sequence data in mammals that have independently evolved echolocation and show for the first time that convergence is not a rare process restricted to a handful of loci but is instead widespread, continuously distributed and commonly driven by natural selection acting on a small number of sites per locus. Systematic analyses of convergent sequence evolution in 805,053 amino acids within 2,326 orthologous coding gene sequences compared across 22 mammals (including four new bat genomes) revealed signatures consistent with convergence in nearly 200 loci. Strong and significant support for convergence among bats and the dolphin was seen in numerous genes linked to hearing or deafness, consistent with an involvement in echolocation. Surprisingly we also found convergence in many genes linked to vision: the convergent signal of many sensory genes was robustly correlated with the strength of natural selection. This first attempt to detect genome-wide convergent sequence evolution across divergent taxa reveals the phenomenon to be much more pervasive than previously recognised. PMID:24005325

  5. Fine-tuning gene networks using simple sequence repeats

    PubMed Central

    Egbert, Robert G.; Klavins, Eric

    2012-01-01

    The parameters in a complex synthetic gene network must be extensively tuned before the network functions as designed. Here, we introduce a simple and general approach to rapidly tune gene networks in Escherichia coli using hypermutable simple sequence repeats embedded in the spacer region of the ribosome binding site. By varying repeat length, we generated expression libraries that incrementally and predictably sample gene expression levels over a 1,000-fold range. We demonstrate the utility of the approach by creating a bistable switch library that programmatically samples the expression space to balance the two states of the switch, and we illustrate the need for tuning by showing that the switch’s behavior is sensitive to host context. Further, we show that mutation rates of the repeats are controllable in vivo for stability or for targeted mutagenesis—suggesting a new approach to optimizing gene networks via directed evolution. This tuning methodology should accelerate the process of engineering functionally complex gene networks. PMID:22927382

  6. Catalyst Stability Benchmarking for the Oxygen Evolution Reaction: The Importance of Backing Electrode Material and Dissolution in Accelerated Aging Studies.

    PubMed

    Geiger, Simon; Kasian, Olga; Mingers, Andrea M; Nicley, Shannon S; Haenen, Ken; Mayrhofer, Karl J J; Cherevko, Serhiy

    2017-09-18

    In searching for alternative oxygen evolution reaction (OER) catalysts for acidic water splitting, fast screening of the material intrinsic activity and stability in half-cell tests is of vital importance. The screening process significantly accelerates the discovery of new promising materials without the need of time-consuming real-cell analysis. In commonly employed tests, a conclusion on the catalyst stability is drawn solely on the basis of electrochemical data, for example, by evaluating potential-versus-time profiles. Herein important limitations of such approaches, which are related to the degradation of the backing electrode material, are demonstrated. State-of-the-art Ir-black powder is investigated for OER activity and for dissolution as a function of the backing electrode material. Even at very short time intervals materials like glassy carbon passivate, increasing the contact resistance and concealing the degradation phenomena of the electrocatalyst itself. Alternative backing electrodes like gold and boron-doped diamond show better stability and are thus recommended for short accelerated aging investigations. Moreover, parallel quantification of dissolution products in the electrolyte is shown to be of great importance for comparing OER catalyst feasibility. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Reconstruction of DNA sequences using genetic algorithms and cellular automata: towards mutation prediction?

    PubMed

    Mizas, Ch; Sirakoulis, G Ch; Mardiris, V; Karafyllidis, I; Glykos, N; Sandaltzopoulos, R

    2008-04-01

    Change of DNA sequence that fuels evolution is, to a certain extent, a deterministic process because mutagenesis does not occur in an absolutely random manner. So far, it has not been possible to decipher the rules that govern DNA sequence evolution due to the extreme complexity of the entire process. In our attempt to approach this issue we focus solely on the mechanisms of mutagenesis and deliberately disregard the role of natural selection. Hence, in this analysis, evolution refers to the accumulation of genetic alterations that originate from mutations and are transmitted through generations without being subjected to natural selection. We have developed a software tool that allows modelling of a DNA sequence as a one-dimensional cellular automaton (CA) with four states per cell which correspond to the four DNA bases, i.e. A, C, T and G. The four states are represented by numbers of the quaternary number system. Moreover, we have developed genetic algorithms (GAs) in order to determine the rules of CA evolution that simulate the DNA evolution process. Linear evolution rules were considered and square matrices were used to represent them. If DNA sequences of different evolution steps are available, our approach allows the determination of the underlying evolution rule(s). Conversely, once the evolution rules are deciphered, our tool may reconstruct the DNA sequence in any previous evolution step for which the exact sequence information was unknown. The developed tool may be used to test various parameters that could influence evolution. We describe a paradigm relying on the assumption that mutagenesis is governed by a near-neighbour-dependent mechanism. Based on the satisfactory performance of our system in the deliberately simplified example, we propose that our approach could offer a starting point for future attempts to understand the mechanisms that govern evolution. The developed software is open-source and has a user-friendly graphical input interface.

  8. Another Look at Strong Ground Motion Accelerations and Stress Drop

    NASA Astrophysics Data System (ADS)

    Baltay, A.; Prieto, G.; Ide, S.; Hanks, T. C.; Beroza, G. C.

    2010-12-01

    The relationship between earthquake stress drop and ground motion acceleration is central to seismic hazard analysis. We revisit measurements of root-mean-square (RMS) acceleration, arms, using KikNet accelerometer data from Japan. We directly measure RMS and peak acceleration, and estimate both apparent stress and corner frequencies using the empirical Green’s function (eGf) coda method of Baltay et al. [2010]. We predict armsfrom corner frequency and stress drop following McGuire and Hanks [1980] to compare with measurements. The theoretical relationship does a good job of predicting observed arms. We use four earthquake sequences in Japan to investigate the source parameters and accelerations: the 2008 Iwate-Miyagi earthquake; the off-Kamaishi repeating sequence; and the 2004 and 2007 Niigata events. In each data set, we choose events that are nearly co-located so that the path term to any station is constant. Small events are used as empirical Green’s functions to correct for propagation effects. For all sequences, we find that the apparent stress averages ~1 MPa for most events. Corner frequencies are consistent with Mo-1/3 scaling. We find the ratio of stress drop and apparent stress to be 5, consistent with the theoretical derivation of Singh and Ordaz [1994], using a Brune [1970] spectra. armsis theoretically proportional to stress drop and the inverse square root of the corner frequency. We show that this calculation can be used as a proxy for armsobservations from strong motion records, using recent data from the four earthquake sequences mentioned above. Even for the Iwate-Miyagi mainshock, which experienced over 4 g’s of acceleration, we find that apparent stress, stress drop and corner frequency follow expected scaling laws and support self-similarity.

  9. Engineering of a target site-specific recombinase by a combined evolution- and structure-guided approach

    PubMed Central

    Abi-Ghanem, Josephine; Chusainow, Janet; Karimova, Madina; Spiegel, Christopher; Hofmann-Sieber, Helga; Hauber, Joachim; Buchholz, Frank; Pisabarro, M. Teresa

    2013-01-01

    Site-specific recombinases (SSRs) can perform DNA rearrangements, including deletions, inversions and translocations when their naive target sequences are placed strategically into the genome of an organism. Hence, in order to employ SSRs in heterologous hosts, their target sites have to be introduced into the genome of an organism before the enzyme can be practically employed. Engineered SSRs hold great promise for biotechnology and advanced biomedical applications, as they promise to extend the usefulness of SSRs to allow efficient and specific recombination of pre-existing, natural genomic sequences. However, the generation of enzymes with desired properties remains challenging. Here, we use substrate-linked directed evolution in combination with molecular modeling to rationally engineer an efficient and specific recombinase (sTre) that readily and specifically recombines a sequence present in the HIV-1 genome. We elucidate the role of key residues implicated in the molecular recognition mechanism and we present a rationale for sTre’s enhanced specificity. Combining evolutionary and rational approaches should help in accelerating the generation of enzymes with desired properties for use in biotechnology and biomedicine. PMID:23275541

  10. Temporal Development of Auroral Acceleration Potentials: High-Altitude Evolutionary Sequences, Drivers and Consequences

    NASA Astrophysics Data System (ADS)

    Hull, A. J.; Wilber, M.; Chaston, C.; Bonnell, J.; Mozer, F.; McFadden, J.; Goldstein, M.; Fillingim, M.

    2007-12-01

    The region above the auroral acceleration region is an integral part of the auroral zone electrodynamic system. At these altitudes (≥ 3 Re) we find the source plasma and fields that determine acceleration processes occurring at lower altitudes, which play a key role in the transport of mass and energy into the ionosphere. Dynamic changes in these high-altitude regions can affect and/or control lower-altitude acceleration processes according to how field-aligned currents and specific plasma sources form and decay and how they are spatially distributed, and through magnetic configuration changes deeper in the magnetotail. Though much progress has been made, the time development and consequential effects of the high-altitude plasma and fields are still not fully understood. We present Cluster multi-point observations at key instances within and above the acceleration region (> 3 RE) of evolving auroral arc current systems. Results are presented from events occurring under different conditions, such as magnetospheric activity, associations with density depletions or gradients, and Alfvenic turbulence. A preliminary survey, primarily at or near the plasma sheet boundary, indicates quasi- static up-down current pair systems are at times associated with density depletions and other instances occur in association with density gradients. The data suggest that such quasi-static current systems may be evolving from structured Alfvenic current systems. We will discuss the temporal development of auroral acceleration potentials, plasma and currents, including quasi-static system formation from turbulent systems of structured Alfvenic field-aligned currents, density depletion and constituent reorganization of the source and ionospheric plasma that transpire in such systems. Of particular emphasis is how temporal changes in magnetospheric source plasma and fields affect the development of auroral acceleration potentials at lower altitudes.

  11. Three-dimensional sampling perfection with application-optimised contrasts using a different flip angle evolutions sequence for routine imaging of the spine: preliminary experience.

    PubMed

    Tins, B; Cassar-Pullicino, V; Haddaway, M; Nachtrab, U

    2012-08-01

    The bulk of spinal imaging is still performed with conventional two-dimensional sequences. This study assesses the suitability of three-dimensional sampling perfection with application-optimised contrasts using a different flip angle evolutions (SPACE) sequence for routine spinal imaging. 62 MRI examinations of the spine were evaluated by 2 examiners in consensus for the depiction of anatomy and presence of artefact. We noted pathologies that might be missed using the SPACE sequence only or the SPACE and a sagittal T(1) weighted sequence. The reference standards were sagittal and axial T(1) weighted and T(2) weighted sequences. At a later date the evaluation was repeated by one of the original examiners and an additional examiner. There was good agreement of the single evaluations and consensus evaluation for the conventional sequences: κ>0.8, confidence interval (CI)>0.6-1.0. For the SPACE sequence, depiction of anatomy was very good for 84% of cases, with high interobserver agreement, but there was poor interobserver agreement for other cases. For artefact assessment of SPACE, κ=0.92, CI=0.92-1.0. The SPACE sequence was superior to conventional sequences for depiction of anatomy and artefact resistance. The SPACE sequence occasionally missed bone marrow oedema. In conjunction with sagittal T(1) weighted sequences, no abnormality was missed. The isotropic SPACE sequence was superior to conventional sequences in imaging difficult anatomy such as in scoliosis and spondylolysis. The SPACE sequence allows excellent assessment of anatomy owing to high spatial resolution and resistance to artefact. The sensitivity for bone marrow abnormalities is limited.

  12. Testing the Role of Multicopy Plasmids in the Evolution of Antibiotic Resistance.

    PubMed

    Escudero, Jose Antonio; MacLean, R Craig; San Millan, Alvaro

    2018-05-02

    Multicopy plasmids are extremely abundant in prokaryotes but their role in bacterial evolution remains poorly understood. We recently showed that the increase in gene copy number per cell provided by multicopy plasmids could accelerate the evolution of plasmid-encoded genes. In this work, we present an experimental system to test the ability of multicopy plasmids to promote gene evolution. Using simple molecular biology methods, we constructed a model system where an antibiotic resistance gene can be inserted into Escherichia coli MG1655, either in the chromosome or on a multicopy plasmid. We use an experimental evolution approach to propagate the different strains under increasing concentrations of antibiotics and we measure survival of bacterial populations over time. The choice of the antibiotic molecule and the resistance gene is so that the gene can only confer resistance through the acquisition of mutations. This "evolutionary rescue" approach provides a simple method to test the potential of multicopy plasmids to promote the acquisition of antibiotic resistance. In the next step of the experimental system, the molecular bases of antibiotic resistance are characterized. To identify mutations responsible for the acquisition of antibiotic resistance we use deep DNA sequencing of samples obtained from whole populations and clones. Finally, to confirm the role of the mutations in the gene under study, we reconstruct them in the parental background and test the resistance phenotype of the resulting strains.

  13. Parameters of proteome evolution from histograms of amino-acid sequence identities of paralogous proteins

    PubMed Central

    Axelsen, Jacob Bock; Yan, Koon-Kiu; Maslov, Sergei

    2007-01-01

    Background The evolution of the full repertoire of proteins encoded in a given genome is mostly driven by gene duplications, deletions, and sequence modifications of existing proteins. Indirect information about relative rates and other intrinsic parameters of these three basic processes is contained in the proteome-wide distribution of sequence identities of pairs of paralogous proteins. Results We introduce a simple mathematical framework based on a stochastic birth-and-death model that allows one to extract some of this information and apply it to the set of all pairs of paralogous proteins in H. pylori, E. coli, S. cerevisiae, C. elegans, D. melanogaster, and H. sapiens. It was found that the histogram of sequence identities p generated by an all-to-all alignment of all protein sequences encoded in a genome is well fitted with a power-law form ~ p-γ with the value of the exponent γ around 4 for the majority of organisms used in this study. This implies that the intra-protein variability of substitution rates is best described by the Gamma-distribution with the exponent α ≈ 0.33. Different features of the shape of such histograms allow us to quantify the ratio between the genome-wide average deletion/duplication rates and the amino-acid substitution rate. Conclusion We separately measure the short-term ("raw") duplication and deletion rates rdup∗, rdel∗ which include gene copies that will be removed soon after the duplication event and their dramatically reduced long-term counterparts rdup, rdel. High deletion rate among recently duplicated proteins is consistent with a scenario in which they didn't have enough time to significantly change their functional roles and thus are to a large degree disposable. Systematic trends of each of the four duplication/deletion rates with the total number of genes in the genome were analyzed. All but the deletion rate of recent duplicates rdel∗ were shown to systematically increase with Ngenes. Abnormally flat shapes

  14. Exploring Connectivity in Sequence Space of Functional RNA

    NASA Technical Reports Server (NTRS)

    Wei, Chenyu; Pohorille, Andrzej; Popovic, Milena; Ditzler, Mark

    2017-01-01

    Emergence of replicable genetic molecules was one of the marking points in the origin of life, evolution of which can be conceptualized as a walk through the space of all possible sequences. A theoretical concept of fitness landscape helps to understand evolutionary processes through assigning a value of fitness to each genotype. Then, evolution of a phenotype is viewed as a series of consecutive, single-point mutations. Natural selection biases evolution toward peaks of high fitness and away from valleys of low fitness. whereas neutral drift occurs in the sequence space without direction as mutations are introduced at random. Large networks of neutral or near-neutral mutations on a fitness landscape, especially for sufficiently long genomes, are possible or even inevitable. Their detection in experiments, however, has been elusive. Although a few near-neutral evolutionary pathways have been found, recent experimental evidence indicates landscapes consist of largely isolated islands. The generality of these results, however, is not clear, as the genome length or the fraction of functional molecules in the genotypic space might have been insufficient for the emergence of large, neutral networks. Thorough investigation on the structure of the fitness landscape is essential to understand the mechanisms of evolution of early genomes. RNA molecules are commonly assumed to play the pivotal role in the origin of genetic systems. They are widely believed to be early, if not the earliest, genetic and catalytic molecules, with abundant biochemical activities as aptamers and ribozymes, i.e. RNA molecules capable, respectively, to bind small molecules or catalyze chemical reactions. Here, we present results of our recent studies on the structure of the sequence space of RNA ligase ribozymes selected through in vitro evolution. Several hundred thousands of sequences active to a different degree were obtained by way of deep sequencing. Analysis of these sequences revealed

  15. Rapid rate of control-region evolution in Pacific butterflyfishes (Chaetodontidae).

    PubMed

    McMillan, W O; Palumbi, S R

    1997-11-01

    Sequence differences in the tRNA-proline (tRNApro) end of the mitochondrial control-region of three species of Pacific butterflyfishes accumulated 33-43 times more rapidly than did changes within the mitochondrial cytochrome b gene (cytb). Rapid evolution in this region was accompanied by strong transition/transversion bias and large variation in the probability of a DNA substitution among sites. These substitution constraints placed an absolute ceiling on the magnitude of sequence divergence that could be detected between individuals. This divergence "ceiling" was reached rapidly and led to a decay in the relative rate of control-region/cytb b evolution. A high rate of evolution in this section of the control-region of butterflyfishes stands in marked contrast to the patterns reported in some other fish lineages. Although the mechanism underlying rate variation remains unclear, all taxa with rapid evolution in the 5'-end of the control-region showed extreme transition biases. By contrast, in taxa with slower control-region evolution, transitions accumulated at nearly the same rate as transversions. More information is needed to understand the relationship between nucleotide bias and the rate of evolution in the 5'-end of the control-region. Despite strong constraints on sequence change, phylogenetic information was preserved in the group of recently differentiated species and supported the clustering of sequences into three major mtDNA groupings. Within these groups, very similar control-region sequences were widely distributed across the Pacific Ocean and were shared between recognized species, indicating a lack of mitochondrial sequence monophyly among species.

  16. The evolution of angular momentum among zero-age main-sequence solar-type stars

    NASA Technical Reports Server (NTRS)

    Soderblom, David R.; Stauffer, John R.; Macgregor, Keith B.; Jones, Burton F.

    1993-01-01

    We consider a survey of rotation among F, G, and K dwarfs of the Pleiades in the context of other young clusters (Alpha Persei and the Hyades) and pre-main-sequence (PMS) stars (in Taurus-Auriga and Orion) in order to examine how the angular momentum of a star like the sun evolves during its early life on the main sequence. The rotation of PMS stars can be evolved into distributions like those seen in the young clusters if there is only modest, rotation-independent angular momentum loss prior to the ZAMS. Even then, the ultrafast rotators (UFRs, or ZAMS G and K dwarfs with v sin i equal to or greater than 30 km/s) must owe their extra angular momentum to their conditions of formation and to different angular momentum loss rates above a threshold velocity, for it is unlikely that these stars had angular momentum added as they neared the ZAMS, nor can a spread in ages within a cluster account for the range of rotation seen. Only a fraction of solar-type stars are thus capable of becoming UFRs, and it is not a phase that all stars experience. Simple scaling relations (like the Skumanich relation) applied to the observed surface rotation rates of young solar-type stars cannot reproduce the way in which the Pleiades evolve into the Hyades. We argue that invoking internal differential rotation in these ZAMS stars can explain several aspects of the observations and thus can provide a consistent picture of ZAMS angular momentum evolution.

  17. Particle accelerator employing transient space charge potentials

    DOEpatents

    Post, Richard F.

    1990-01-01

    The invention provides an accelerator for ions and charged particles. The plasma is generated and confined in a magnetic mirror field. The electrons of the plasma are heated to high temperatures. A series of local coils are placed along the axis of the magnetic mirror field. As an ion or particle beam is directed along the axis in sequence the coils are rapidly pulsed creating a space charge to accelerate and focus the beam of ions or charged particles.

  18. Accelerated Radiation-Damping for Increased Spin Equilibrium (ARISE)

    PubMed Central

    Huang, Susie Y.; Witzel, Thomas; Wald, Lawrence L.

    2008-01-01

    Control of the longitudinal magnetization in fast gradient echo sequences is an important factor enabling the high efficiency of balanced Steady State Free Precession (bSSFP) sequences. We introduce a new method for accelerating the return of the longitudinal magnetization to the +z-axis that is independent of externally applied RF pulses and shows improved off-resonance performance. The Accelerated Radiation damping for Increased Spin Equilibrium (ARISE) method uses an external feedback circuit to strengthen the Radiation Damping (RD) field. The enhanced RD field rotates the magnetization back to the +z-axis at a rate faster than T1 relaxation. The method is characterized in gradient echo phantom imaging at 3T as a function of feedback gain, phase, and duration and compared with results from numerical simulations of the Bloch equations incorporating RD. A short period of feedback (10ms) during a refocused interval of a crushed gradient echo sequence allowed greater than 99% recovery of the longitudinal magnetization when very little T2 relaxation has time to occur. Appropriate applications might include improving navigated sequences. Unlike conventional flip-back schemes, the ARISE “flip-back” is generated by the spins themselves, thereby offering a potentially useful building block for enhancing gradient echo sequences. PMID:18956463

  19. Novel Arenavirus Sequences in Hylomyscus sp. and Mus (Nannomys) setulosus from Côte d'Ivoire: Implications for Evolution of Arenaviruses in Africa

    PubMed Central

    Kouassi, Stéphane K.; Fichet-Calvet, Elisabeth; Becker-Ziaja, Beate; Rieger, Toni; Ölschläger, Stephan; Dosso, Hernri; Denys, Christiane; ter Meulen, Jan; Akoua-Koffi, Chantal; Günther, Stephan

    2011-01-01

    This study aimed to identify new arenaviruses and gather insights in the evolution of arenaviruses in Africa. During 2003 through 2005, 1,228 small mammals representing 14 different genera were trapped in 9 villages in south, east, and middle west of Côte d'Ivoire. Specimens were screened by pan-Old World arenavirus RT-PCRs targeting S and L RNA segments as well as immunofluorescence assay. Sequences of two novel tentative species of the family Arenaviridae, Menekre and Gbagroube virus, were detected in Hylomyscus sp. and Mus (Nannomys) setulosus, respectively. Arenavirus infection of Mus (Nannomys) setulosus was also demonstrated by serological testing. Lassa virus was not found, although 60% of the captured animals were Mastomys natalensis. Complete S RNA and partial L RNA sequences of the novel viruses were recovered from the rodent specimens and subjected to phylogenetic analysis. Gbagroube virus is a closely related sister taxon of Lassa virus, while Menekre virus clusters with the Ippy/Mobala/Mopeia virus complex. Reconstruction of possible virus–host co-phylogeny scenarios suggests that, within the African continent, signatures of co-evolution might have been obliterated by multiple host-switching events. PMID:21695269

  20. PARALLEL RACE FORMATION AND THE EVOLUTION OF MIMICRY IN HELICONIUS BUTTERFLIES: A PHYLOGENETIC HYPOTHESIS FROM MITOCHONDRIAL DNA SEQUENCES.

    PubMed

    Brower, Andrew V Z

    1996-02-01

    Mimicry has been a fundamental focus of research since the birth of evolutionary biology yet rarely has been studied from a phylogenetic perspective beyond the simple recognition that mimics are not similar due to common descent. The difficulty of finding characters to discern relationships among closely related and convergent taxa has challenged systematists for more than a century. The phenotypic diversity of wing pattens among mimetic Heliconius adds an additional twist to the problem, because single species contain more than a dozen radically different-looking geographical races even though the mimetic advantage is theoretically highest when all individuals within and between species appear the same. Mitochondrial DNA (mtDNA) offers an independent way to address these issues. In this study, Cytochrome Oxidase I and II sequences from multiple, parallel races of Heliconius erato and Heliconius melpomene are examined, to estimate intraspecific phylogeny and gauge sequence divergence and ages of clades among races within each species. Although phenotypes of sympatric races exhibit remarkable concordance between the two species, the mitochondrial cladograms show that the species have not shared a common evolutionary history. H. erato exhibits a basal split between trans- and cis-Andean groups of races, whereas H. melpomene originates in the Guiana Shield. Diverse races in either species appear to have evolved within the last 200,000 yr, and convergent phenotypes have evolved independently within as well as between species. These results contradict prior theories of the evolution of mimicry based on analysis of wing-pattern genetics. © 1996 The Society for the Study of Evolution.

  1. Microbial evolution of sulphate reduction when lateral gene transfer is geographically restricted.

    PubMed

    Chi Fru, E

    2011-07-01

    Lateral gene transfer (LGT) is an important mechanism by which micro-organisms acquire new functions. This process has been suggested to be central to prokaryotic evolution in various environments. However, the influence of geographical constraints on the evolution of laterally acquired genes in microbial metabolic evolution is not yet well understood. In this study, the influence of geographical isolation on the evolution of laterally acquired dissimilatory sulphite reductase (dsr) gene sequences in the sulphate-reducing micro-organisms (SRM) was investigated. Sequences on four continental blocks related to SRM known to have received dsr by LGT were analysed using standard phylogenetic and multidimensional statistical methods. Sequences related to lineages with large genetic diversity correlated positively with habitat divergence. Those affiliated to Thermodesulfobacterium indicated strong biogeographical delineation; hydrothermal-vent sequences clustered independently from hot-spring sequences. Some of the hydrothermal-vent and hot-spring sequences suggested to have been acquired from a common ancestral source may have diverged upon isolation within distinct habitats. In contrast, analysis of some Desulfotomaculum sequences indicated they could have been transferred from different ancestral sources but converged upon isolation within the same niche. These results hint that, after lateral acquisition of dsr genes, barriers to gene flow probably play a strong role in their subsequent evolution.

  2. Visualizing Clonal Evolution in Cancer.

    PubMed

    Krzywinski, Martin

    2016-06-02

    Rapid and inexpensive single-cell sequencing is driving new visualizations of cancer instability and evolution. Krzywinski discusses how to present clone evolution plots in order to visualize temporal, phylogenetic, and spatial aspects of a tumor in a single static image. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. First complete mitochondrial genome sequence from a box jellyfish reveals a highly fragmented linear architecture and insights into telomere evolution.

    PubMed

    Smith, David Roy; Kayal, Ehsan; Yanagihara, Angel A; Collins, Allen G; Pirro, Stacy; Keeling, Patrick J

    2012-01-01

    Animal mitochondrial DNAs (mtDNAs) are typically single circular chromosomes, with the exception of those from medusozoan cnidarians (jellyfish and hydroids), which are linear and sometimes fragmented. Most medusozoans have linear monomeric or linear bipartite mitochondrial genomes, but preliminary data have suggested that box jellyfish (cubozoans) have mtDNAs that consist of many linear chromosomes. Here, we present the complete mtDNA sequence from the winged box jellyfish Alatina moseri (the first from a cubozoan). This genome contains unprecedented levels of fragmentation: 18 unique genes distributed over eight 2.9- to 4.6-kb linear chromosomes. The telomeres are identical within and between chromosomes, and recombination between subtelomeric sequences has led to many genes initiating or terminating with sequences from other genes (the most extreme case being 150 nt of a ribosomal RNA containing the 5' end of nad2), providing evidence for a gene conversion-based model of telomere evolution. The silent-site nucleotide variation within the A. moseri mtDNA is among the highest observed from a eukaryotic genome and may be associated with elevated rates of recombination.

  4. Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin

    PubMed Central

    Hauck, Nastasja C.; Kirpach, Josiane; Kiefer, Christina; Farinelle, Sophie; Morris, Stephen A.; Muller, Claude P.; Lu, I-Na

    2018-01-01

    To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH). Our vaccine targeting LAH of hemagglutinin elicited significant seroconversion and protection against homologous and heterologous influenza virus strains in mice. The vaccine not only significantly reduced lung viral titers, but also induced a well-known bottleneck effect by decreasing virus diversity. In contrast to the classical bottleneck effect, here we showed a significant increase in the frequency of viruses with amino acid sequences identical to that of vaccine targeting LAH domain. No escape mutant emerged after vaccination. These results not only support the potential of a universal influenza vaccine targeting the conserved LAH domains, but also clearly demonstrate that the well-established bottleneck effect on viral quasispecies evolution does not necessarily generate escape mutants. PMID:29587397

  5. Insights into the Evolution of Mitochondrial Genome Size from Complete Sequences of Citrullus lanatus and Cucurbita pepo (Cucurbitaceae)

    PubMed Central

    Alverson, Andrew J.; Wei, XiaoXin; Rice, Danny W.; Stern, David B.; Barry, Kerrie; Palmer, Jeffrey D.

    2010-01-01

    The mitochondrial genomes of seed plants are unusually large and vary in size by at least an order of magnitude. Much of this variation occurs within a single family, the Cucurbitaceae, whose genomes range from an estimated 390 to 2,900 kb in size. We sequenced the mitochondrial genomes of Citrullus lanatus (watermelon: 379,236 nt) and Cucurbita pepo (zucchini: 982,833 nt)—the two smallest characterized cucurbit mitochondrial genomes—and determined their RNA editing content. The relatively compact Citrullus mitochondrial genome actually contains more and longer genes and introns, longer segmental duplications, and more discernibly nuclear-derived DNA. The large size of the Cucurbita mitochondrial genome reflects the accumulation of unprecedented amounts of both chloroplast sequences (>113 kb) and short repeated sequences (>370 kb). A low mutation rate has been hypothesized to underlie increases in both genome size and RNA editing frequency in plant mitochondria. However, despite its much larger genome, Cucurbita has a significantly higher synonymous substitution rate (and presumably mutation rate) than Citrullus but comparable levels of RNA editing. The evolution of mutation rate, genome size, and RNA editing are apparently decoupled in Cucurbitaceae, reflecting either simple stochastic variation or governance by different factors. PMID:20118192

  6. Three-dimensional sampling perfection with application-optimised contrasts using a different flip angle evolutions sequence for routine imaging of the spine: preliminary experience

    PubMed Central

    Tins, B; Cassar-Pullicino, V; Haddaway, M; Nachtrab, U

    2012-01-01

    Objectives The bulk of spinal imaging is still performed with conventional two-dimensional sequences. This study assesses the suitability of three-dimensional sampling perfection with application-optimised contrasts using a different flip angle evolutions (SPACE) sequence for routine spinal imaging. Methods 62 MRI examinations of the spine were evaluated by 2 examiners in consensus for the depiction of anatomy and presence of artefact. We noted pathologies that might be missed using the SPACE sequence only or the SPACE and a sagittal T1 weighted sequence. The reference standards were sagittal and axial T1 weighted and T2 weighted sequences. At a later date the evaluation was repeated by one of the original examiners and an additional examiner. Results There was good agreement of the single evaluations and consensus evaluation for the conventional sequences: κ>0.8, confidence interval (CI)>0.6–1.0. For the SPACE sequence, depiction of anatomy was very good for 84% of cases, with high interobserver agreement, but there was poor interobserver agreement for other cases. For artefact assessment of SPACE, κ=0.92, CI=0.92–1.0. The SPACE sequence was superior to conventional sequences for depiction of anatomy and artefact resistance. The SPACE sequence occasionally missed bone marrow oedema. In conjunction with sagittal T1 weighted sequences, no abnormality was missed. The isotropic SPACE sequence was superior to conventional sequences in imaging difficult anatomy such as in scoliosis and spondylolysis. Conclusion The SPACE sequence allows excellent assessment of anatomy owing to high spatial resolution and resistance to artefact. The sensitivity for bone marrow abnormalities is limited. PMID:22374284

  7. Genetic diversity and molecular evolution of Naga King Chili inferred from internal transcribed spacer sequence of nuclear ribosomal DNA.

    PubMed

    Kehie, Mechuselie; Kumaria, Suman; Devi, Khumuckcham Sangeeta; Tandon, Pramod

    2016-02-01

    Sequences of the Internal Transcribed Spacer (ITS1-5.8S-ITS2) of nuclear ribosomal DNAs were explored to study the genetic diversity and molecular evolution of Naga King Chili. Our study indicated the occurrence of nucleotide polymorphism and haplotypic diversity in the ITS regions. The present study demonstrated that the variability of ITS1 with respect to nucleotide diversity and sequence polymorphism exceeded that of ITS2. Sequence analysis of 5.8S gene revealed a much conserved region in all the accessions of Naga King Chili. However, strong phylogenetic information of this species is the distinct 13 bp deletion in the 5.8S gene which discriminated Naga King Chili from the rest of the Capsicum sp. Neutrality test results implied a neutral variation, and population seems to be evolving at drift-mutation equilibrium and free from directed selection pressure. Furthermore, mismatch analysis showed multimodal curve indicating a demographic equilibrium. Phylogenetic relationships revealed by Median Joining Network (MJN) analysis denoted a clear discrimination of Naga King Chili from its closest sister species (Capsicum chinense and Capsicum frutescens). The absence of star-like network of haplotypes suggested an ancient population expansion of this chili.

  8. Distribution uniformity of laser-accelerated proton beams

    NASA Astrophysics Data System (ADS)

    Zhu, Jun-Gao; Zhu, Kun; Tao, Li; Xu, Xiao-Han; Lin, Chen; Ma, Wen-Jun; Lu, Hai-Yang; Zhao, Yan-Ying; Lu, Yuan-Rong; Chen, Jia-Er; Yan, Xue-Qing

    2017-09-01

    Compared with conventional accelerators, laser plasma accelerators can generate high energy ions at a greatly reduced scale, due to their TV/m acceleration gradient. A compact laser plasma accelerator (CLAPA) has been built at the Institute of Heavy Ion Physics at Peking University. It will be used for applied research like biological irradiation, astrophysics simulations, etc. A beamline system with multiple quadrupoles and an analyzing magnet for laser-accelerated ions is proposed here. Since laser-accelerated ion beams have broad energy spectra and large angular divergence, the parameters (beam waist position in the Y direction, beam line layout, drift distance, magnet angles etc.) of the beamline system are carefully designed and optimised to obtain a radially symmetric proton distribution at the irradiation platform. Requirements of energy selection and differences in focusing or defocusing in application systems greatly influence the evolution of proton distributions. With optimal parameters, radially symmetric proton distributions can be achieved and protons with different energy spread within ±5% have similar transverse areas at the experiment target. Supported by National Natural Science Foundation of China (11575011, 61631001) and National Grand Instrument Project (2012YQ030142)

  9. Manipulation of quantum evolution

    NASA Technical Reports Server (NTRS)

    Cabera, David Jose Fernandez; Mielnik, Bogdan

    1994-01-01

    The free evolution of a non-relativistic charged particle is manipulated using time-dependent magnetic fields. It is shown that the application of a programmed sequence of magnetic pulses can invert the free evolution process, forcing an arbitrary wave packet to 'go back in time' to recover its past shape. The possibility of more general operations upon the Schrodinger wave packet is discussed.

  10. Expression Divergence Is Correlated with Sequence Evolution but Not Positive Selection in Conifers.

    PubMed

    Hodgins, Kathryn A; Yeaman, Sam; Nurkowski, Kristin A; Rieseberg, Loren H; Aitken, Sally N

    2016-06-01

    The evolutionary and genomic determinants of sequence evolution in conifers are poorly understood, and previous studies have found only limited evidence for positive selection. Using RNAseq data, we compared gene expression profiles to patterns of divergence and polymorphism in 44 seedlings of lodgepole pine (Pinus contorta) and 39 seedlings of interior spruce (Picea glauca × engelmannii) to elucidate the evolutionary forces that shape their genomes and their plastic responses to abiotic stress. We found that rapidly diverging genes tend to have greater expression divergence, lower expression levels, reduced levels of synonymous site diversity, and longer proteins than slowly diverging genes. Similar patterns were identified for the untranslated regions, but with some exceptions. We found evidence that genes with low expression levels had a larger fraction of nearly neutral sites, suggesting a primary role for negative selection in determining the association between evolutionary rate and expression level. There was limited evidence for differences in the rate of positive selection among genes with divergent versus conserved expression profiles and some evidence supporting relaxed selection in genes diverging in expression between the species. Finally, we identified a small number of genes that showed evidence of site-specific positive selection using divergence data alone. However, estimates of the proportion of sites fixed by positive selection (α) were in the range of other plant species with large effective population sizes suggesting relatively high rates of adaptive divergence among conifers. © The Author 2016. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  11. Sequence-specific antimicrobials using efficiently delivered RNA-guided nucleases.

    PubMed

    Citorik, Robert J; Mimee, Mark; Lu, Timothy K

    2014-11-01

    Current antibiotics tend to be broad spectrum, leading to indiscriminate killing of commensal bacteria and accelerated evolution of drug resistance. Here, we use CRISPR-Cas technology to create antimicrobials whose spectrum of activity is chosen by design. RNA-guided nucleases (RGNs) targeting specific DNA sequences are delivered efficiently to microbial populations using bacteriophage or bacteria carrying plasmids transmissible by conjugation. The DNA targets of RGNs can be undesirable genes or polymorphisms, including antibiotic resistance and virulence determinants in carbapenem-resistant Enterobacteriaceae and enterohemorrhagic Escherichia coli. Delivery of RGNs significantly improves survival in a Galleria mellonella infection model. We also show that RGNs enable modulation of complex bacterial populations by selective knockdown of targeted strains based on genetic signatures. RGNs constitute a class of highly discriminatory, customizable antimicrobials that enact selective pressure at the DNA level to reduce the prevalence of undesired genes, minimize off-target effects and enable programmable remodeling of microbiota.

  12. Post-main-sequence planetary system evolution

    PubMed Central

    Veras, Dimitri

    2016-01-01

    The fates of planetary systems provide unassailable insights into their formation and represent rich cross-disciplinary dynamical laboratories. Mounting observations of post-main-sequence planetary systems necessitate a complementary level of theoretical scrutiny. Here, I review the diverse dynamical processes which affect planets, asteroids, comets and pebbles as their parent stars evolve into giant branch, white dwarf and neutron stars. This reference provides a foundation for the interpretation and modelling of currently known systems and upcoming discoveries. PMID:26998326

  13. Post-main-sequence planetary system evolution.

    PubMed

    Veras, Dimitri

    2016-02-01

    The fates of planetary systems provide unassailable insights into their formation and represent rich cross-disciplinary dynamical laboratories. Mounting observations of post-main-sequence planetary systems necessitate a complementary level of theoretical scrutiny. Here, I review the diverse dynamical processes which affect planets, asteroids, comets and pebbles as their parent stars evolve into giant branch, white dwarf and neutron stars. This reference provides a foundation for the interpretation and modelling of currently known systems and upcoming discoveries.

  14. The effects of sex-biased gene expression and X-linkage on rates of sequence evolution in Drosophila.

    PubMed

    Campos, José Luis; Johnston, Keira; Charlesworth, Brian

    2017-12-08

    A faster rate of adaptive evolution of X-linked genes compared with autosomal genes (the faster-X effect) can be caused by the fixation of recessive or partially recessive advantageous mutations. This effect should be largest for advantageous mutations that affect only male fitness, and least for mutations that affect only female fitness. We tested these predictions in Drosophila melanogaster by using coding and functionally significant non-coding sequences of genes with different levels of sex-biased expression. Consistent with theory, nonsynonymous substitutions in most male-biased and unbiased genes show faster adaptive evolution on the X. However, genes with very low recombination rates do not show such an effect, possibly as a consequence of Hill-Robertson interference. Contrary to expectation, there was a substantial faster-X effect for female-biased genes. After correcting for recombination rate differences, however, female-biased genes did not show a faster X-effect. Similar analyses of non-coding UTRs and long introns showed a faster-X effect for all groups of genes, other than introns of female-biased genes. Given the strong evidence that deleterious mutations are mostly recessive or partially recessive, we would expect a slower rate of evolution of X-linked genes for slightly deleterious mutations that become fixed by genetic drift. Surprisingly, we found little evidence for this after correcting for recombination rate, implying that weakly deleterious mutations are mostly close to being semidominant. This is consistent with evidence from polymorphism data, which we use to test how models of selection that assume semidominance with no sex-specific fitness effects may bias estimates of purifying selection. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  15. Chloroplast DNA analysis of Tunisian cork oak populations (Quercus suber L.): sequence variations and molecular evolution of the trnL (UAA)-trnF (GAA) region.

    PubMed

    Abdessamad, A; Baraket, G; Sakka, H; Ammari, Y; Ksontini, M; Hannachi, A Salhi

    2016-10-24

    Sequences of the trnL-trnF spacer and combined trnL-trnF region in chloroplast DNA of cork oak (Quercus suber L.) were analyzed to detect polymorphisms and to elucidate molecular evolution and demographic history. The aligned sequences varied in length and nucleotide composition. The overall ratio of transition/transversion (ti/tv) of 0.724 for the intergenic spacer and 0.258 for the pooled sequences were estimated, and indicated that transversions are more frequent than transitions. The molecular evolution and demographic history of Q. suber were investigated. Neutrality tests (Tajima's D and Fu and Li) ruled out the null hypothesis of a strictly neutral model, and Fu's Fs and Ramos-Onsins and Rozas' R2 confirmed the recent expansion of cork oak trees, validating its persistency in North Africa since the last glaciation during the Quaternary. The observed uni-modal mismatch distribution and the Harpending's raggedness index confirmed the demographic history model for cork oak. A phylogenetic dendrogram showed that the distribution of Q. suber trees occurs independently of geographical origin, the relief of the population site, and the bioclimatic stages. The molecular history and cytoplasmic diversity suggest that in situ and ex situ conservation strategies can be recommended for preserving landscape value and facing predictable future climatic changes.

  16. Evaluating secular acceleration in geomagnetic field model GRIMM-3

    NASA Astrophysics Data System (ADS)

    Lesur, V.; Wardinski, I.

    2012-12-01

    Secular acceleration of the magnetic field is the rate of change of its secular variation. One of the main results of studying magnetic data collected by the German survey satellite CHAMP was the mapping of field acceleration and its evolution in time. Questions remain about the accuracy of the modeled acceleration and the effect of the applied regularization processes. We have evaluated to what extent the regularization affects the temporal variability of the Gauss coefficients. We also obtained results of temporal variability of the Gauss coefficients where alternative approaches to the usual smoothing norms have been applied for regularization. Except for the dipole term, the secular acceleration of the Gauss coefficients is fairly well described up to spherical harmonic degree 5 or 6. There is no clear evidence from observatory data that the spectrum of this acceleration is underestimated at the Earth surface. Assuming a resistive mantle, the observed acceleration supports a characteristic time scale for the secular variation of the order of 11 years.

  17. Constraints in cancer evolution.

    PubMed

    Venkatesan, Subramanian; Birkbak, Nicolai J; Swanton, Charles

    2017-02-08

    Next-generation deep genome sequencing has only recently allowed us to quantitatively dissect the extent of heterogeneity within a tumour, resolving patterns of cancer evolution. Intratumour heterogeneity and natural selection contribute to resistance to anticancer therapies in the advanced setting. Recent evidence has also revealed that cancer evolution might be constrained. In this review, we discuss the origins of intratumour heterogeneity and subsequently focus on constraints imposed upon cancer evolution. The presence of (1) parallel evolution, (2) convergent evolution and (3) the biological impact of acquiring mutations in specific orders suggest that cancer evolution may be exploitable. These constraints on cancer evolution may help us identify cancer evolutionary rule books, which could eventually inform both diagnostic and therapeutic approaches to improve survival outcomes. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  18. Evolution of MHC class I genes in the endangered loggerhead sea turtle (Caretta caretta) revealed by 454 amplicon sequencing.

    PubMed

    Stiebens, Victor A; Merino, Sonia E; Chain, Frédéric J J; Eizaguirre, Christophe

    2013-04-30

    In evolutionary and conservation biology, parasitism is often highlighted as a major selective pressure. To fight against parasites and pathogens, genetic diversity of the immune genes of the major histocompatibility complex (MHC) are particularly important. However, the extensive degree of polymorphism observed in these genes makes it difficult to conduct thorough population screenings. We utilized a genotyping protocol that uses 454 amplicon sequencing to characterize the MHC class I in the endangered loggerhead sea turtle (Caretta caretta) and to investigate their evolution at multiple relevant levels of organization. MHC class I genes revealed signatures of trans-species polymorphism across several reptile species. In the studied loggerhead turtle individuals, it results in the maintenance of two ancient allelic lineages. We also found that individuals carrying an intermediate number of MHC class I alleles are larger than those with either a low or high number of alleles. Multiple modes of evolution seem to maintain MHC diversity in the loggerhead turtles, with relatively high polymorphism for an endangered species.

  19. Accelerated cosmological expansion without tension in the Hubble parameter. Fast evolution of the Hubble parameter H(z)

    NASA Astrophysics Data System (ADS)

    van Putten, Maurice H. P. M.

    2018-01-01

    The H0-tension problem poses a confrontation of dark energy driving latetime cosmological expansion measured by the Hubble parameter H(z) over an extended range of redshifts z. Distinct values H0 ≃ 73 km s-1 Mpcs-1 and H0 ≃ 68 km s-1 Mpcs-1 obtain from surveys of the Local Universe and, respectively, ΛCBM analysis of the CMB. These are representative of accelerated expansion with H'(0) ≃ 0 by and, respectively, H'(0) > 0 in ΛCDM, where is a fundamental frequency of the cosmological horizon in a Friedmann-Robertson-Walker universe with deceleration parameter q(z) = -1 + (1+z)H-1 H'(z). Explicit solution H(z) = H0 and, respectively, H(z) = H0 are here compared with recent data on H(z) over 0 ≲ z ≲ 2.The first is found to be free of tension with H0 from local surveys, while the latter is disfavored at 2:7σ A further confrontation obtains in galaxy dynamics by a finite sensitivity of inertia to background cosmology in weak gravity, putting an upper bound of m ≲ 10-30 eV on the mass of dark matter. A C0 onset to weak gravity at the de Sitter scale of acceleration adS = cH(z), where c denotes the velocity of light, can be seen in galaxy rotation curves covering 0 ≲ z ≲ 2 Weak gravity in galaxy dynamics hereby provides a proxy for cosmological evolution.

  20. History and Technology Developments of Radio Frequency (RF) Systems for Particle Accelerators

    NASA Astrophysics Data System (ADS)

    Nassiri, A.; Chase, B.; Craievich, P.; Fabris, A.; Frischholz, H.; Jacob, J.; Jensen, E.; Jensen, M.; Kustom, R.; Pasquinelli, R.

    2016-04-01

    This article attempts to give a historical account and review of technological developments and innovations in radio frequency (RF) systems for particle accelerators. The evolution from electrostatic field to the use of RF voltage suggested by R. Wideröe made it possible to overcome the shortcomings of electrostatic accelerators, which limited the maximum achievable electric field due to voltage breakdown. After an introduction, we will provide reviews of technological developments of RF systems for particle accelerators.

  1. Gene Tree Discordance Does Not Explain Away the Temporal Decline of Convergence in Mammalian Protein Sequence Evolution.

    PubMed

    Zou, Zhengting; Zhang, Jianzhi

    2017-07-01

    Several authors reported lower frequencies of protein sequence convergence between more distantly related evolutionary lineages and attributed this trend to epistasis, which renders the acceptable amino acids at a site more different and convergence less likely in more divergent lineages. A recent primate study, however, suggested that this trend is at least partially and potentially entirely an artifact of gene tree discordance (GTD). Here, we demonstrate in a genome-wide data set from 17 mammals that the temporal trend remains (1) upon the control of the GTD level, (2) in genes whose genealogies are concordant with the species tree, and (3) for convergent changes, which are extremely unlikely to be caused by GTD. Similar results are observed in a comparable data set of 12 fruit flies in some but not all of these tests. We conclude that, at least in some cases, the temporal decline of convergence is genuine, reflecting an impact of epistasis on protein evolution. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Negative correlation between rates of molecular evolution and flowering cycles in temperate woody bamboos revealed by plastid phylogenomics.

    PubMed

    Ma, Peng-Fei; Vorontsova, Maria S; Nanjarisoa, Olinirina Prisca; Razanatsoa, Jacqueline; Guo, Zhen-Hua; Haevermans, Thomas; Li, De-Zhu

    2017-12-21

    Heterogeneous rates of molecular evolution are universal across the tree of life, posing challenges for phylogenetic inference. The temperate woody bamboos (tribe Arundinarieae, Poaceae) are noted for their extremely slow molecular evolutionary rates, supposedly caused by their mysterious monocarpic reproduction. However, the correlation between substitution rates and flowering cycles has not been formally tested. Here we present 15 newly sequenced plastid genomes of temperate woody bamboos, including the first genomes ever sequenced from Madagascar representatives. A data matrix of 46 plastid genomes representing all 12 lineages of Arundinarieae was assembled for phylogenetic and molecular evolutionary analyses. We conducted phylogenetic analyses using different sequences (e.g., coding and noncoding) combined with different data partitioning schemes, revealing conflicting relationships involving internodes among several lineages. A great difference in branch lengths were observed among the major lineages, and topological inconsistency could be attributed to long-branch attraction (LBA). Using clock model-fitting by maximum likelihood and Bayesian approaches, we furthermore demonstrated extensive rate variation among these major lineages. Rate accelerations mainly occurred for the isolated lineages with limited species diversification, totaling 11 rate shifts during the tribe's evolution. Using linear regression analysis, we found a negative correlation between rates of molecular evolution and flowering cycles for Arundinarieae, notwithstanding that the correlation maybe insignificant when taking the phylogenetic structure into account. Using the temperate woody bamboos as an example, we found further evidence that rate heterogeneity is universal in plants, suggesting that this will pose a challenge for phylogenetic reconstruction of bamboos. The bamboos with longer flowering cycles tend to evolve more slowly than those with shorter flowering cycles, in accordance

  3. A new molecular evolution model for limited insertion independent of substitution.

    PubMed

    Lèbre, Sophie; Michel, Christian J

    2013-10-01

    We recently introduced a new molecular evolution model called the IDIS model for Insertion Deletion Independent of Substitution [13,14]. In the IDIS model, the three independent processes of substitution, insertion and deletion of residues have constant rates. In order to control the genome expansion during evolution, we generalize here the IDIS model by introducing an insertion rate which decreases when the sequence grows and tends to 0 for a maximum sequence length nmax. This new model, called LIIS for Limited Insertion Independent of Substitution, defines a matrix differential equation satisfied by a vector P(t) describing the sequence content in each residue at evolution time t. An analytical solution is obtained for any diagonalizable substitution matrix M. Thus, the LIIS model gives an expression of the sequence content vector P(t) in each residue under evolution time t as a function of the eigenvalues and the eigenvectors of matrix M, the residue insertion rate vector R, the total insertion rate r, the initial and maximum sequence lengths n0 and nmax, respectively, and the sequence content vector P(t0) at initial time t0. The derivation of the analytical solution is much more technical, compared to the IDIS model, as it involves Gauss hypergeometric functions. Several propositions of the LIIS model are derived: proof that the IDIS model is a particular case of the LIIS model when the maximum sequence length nmax tends to infinity, fixed point, time scale, time step and time inversion. Using a relation between the sequence length l and the evolution time t, an expression of the LIIS model as a function of the sequence length l=n(t) is obtained. Formulas for 'insertion only', i.e. when the substitution rates are all equal to 0, are derived at evolution time t and sequence length l. Analytical solutions of the LIIS model are explicitly derived, as a function of either evolution time t or sequence length l, for two classical substitution matrices: the 3

  4. Insight into the evolution and origin of leprosy bacilli from the genome sequence of Mycobacterium lepromatosis

    PubMed Central

    Singh, Pushpendra; Benjak, Andrej; Schuenemann, Verena J.; Herbig, Alexander; Avanzi, Charlotte; Busso, Philippe; Nieselt, Kay; Krause, Johannes; Vera-Cabrera, Lucio; Cole, Stewart T.

    2015-01-01

    Mycobacterium lepromatosis is an uncultured human pathogen associated with diffuse lepromatous leprosy and a reactional state known as Lucio's phenomenon. By using deep sequencing with and without DNA enrichment, we obtained the near-complete genome sequence of M. lepromatosis present in a skin biopsy from a Mexican patient, and compared it with that of Mycobacterium leprae, which has undergone extensive reductive evolution. The genomes display extensive synteny and are similar in size (∼3.27 Mb). Protein-coding genes share 93% nucleotide sequence identity, whereas pseudogenes are only 82% identical. The events that led to pseudogenization of 50% of the genome likely occurred before divergence from their most recent common ancestor (MRCA), and both M. lepromatosis and M. leprae have since accumulated new pseudogenes or acquired specific deletions. Functional comparisons suggest that M. lepromatosis has lost several enzymes required for amino acid synthesis whereas M. leprae has a defective heme pathway. M. lepromatosis has retained all functions required to infect the Schwann cells of the peripheral nervous system and therefore may also be neuropathogenic. A phylogeographic survey of 227 leprosy biopsies by differential PCR revealed that 221 contained M. leprae whereas only six, all from Mexico, harbored M. lepromatosis. Phylogenetic comparisons indicate that M. lepromatosis is closer than M. leprae to the MRCA, and a Bayesian dating analysis suggests that they diverged from their MRCA approximately 13.9 Mya. Thus, despite their ancient separation, the two leprosy bacilli are remarkably conserved and still cause similar pathologic conditions. PMID:25831531

  5. Evolution of domain promiscuity in eukaryotic genomes—a perspective from the inferred ancestral domain architectures†

    PubMed Central

    Cohen-Gihon, Inbar; Fong, Jessica H.; Sharan, Roded; Nussinov, Ruth

    2012-01-01

    Most eukaryotic proteins are composed of two or more domains. These assemble in a modular manner to create new proteins usually by the acquisition of one or more domains to an existing protein. Promiscuous domains which are found embedded in a variety of proteins and co-exist with many other domains are of particular interest and were shown to have roles in signaling pathways and mediating network communication. The evolution of domain promiscuity is still an open problem, mostly due to the lack of sequenced ancestral genomes. Here we use inferred domain architectures of ancestral genomes to trace the evolution of domain promiscuity in eukaryotic genomes. We find an increase in average promiscuity along many branches of the eukaryotic tree. Moreover, domain promiscuity can proceed at almost a steady rate over long evolutionary time or exhibit lineage-specific acceleration. We also observe that many signaling and regulatory domains gained domain promiscuity around the Bilateria divergence. In addition we show that those domains that played a role in the creation of two body axes and existed before the divergence of the bilaterians from fungi/metazoan achieve a boost in their promiscuities during the bilaterian evolution. PMID:21127809

  6. Genomic investigations of evolutionary dynamics and epistasis in microbial evolution experiments.

    PubMed

    Jerison, Elizabeth R; Desai, Michael M

    2015-12-01

    Microbial evolution experiments enable us to watch adaptation in real time, and to quantify the repeatability and predictability of evolution by comparing identical replicate populations. Further, we can resurrect ancestral types to examine changes over evolutionary time. Until recently, experimental evolution has been limited to measuring phenotypic changes, or to tracking a few genetic markers over time. However, recent advances in sequencing technology now make it possible to extensively sequence clones or whole-population samples from microbial evolution experiments. Here, we review recent work exploiting these techniques to understand the genomic basis of evolutionary change in experimental systems. We first focus on studies that analyze the dynamics of genome evolution in microbial systems. We then survey work that uses observations of sequence evolution to infer aspects of the underlying fitness landscape, concentrating on the epistatic interactions between mutations and the constraints these interactions impose on adaptation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  7. Mechanisms of force production during linear accelerations in bluegill sunfish Lepomis macrochirus

    NASA Astrophysics Data System (ADS)

    Tytell, Eric D.; Wise, Tyler N.; Boden, Alexandra L.; Sanders, Erin K.; Schwalbe, Margot A. B.

    2016-11-01

    In nature, fish rarely swim steadily. Although unsteady behaviors are common, we know little about how fish change their swimming kinematics for routine accelerations, and how these changes affect the fluid dynamic forces and the wake produced. To study force production during acceleration, particle image velocimetry was used to quantify the wake of bluegill sunfish Lepomis macrochirus and to estimate the pressure field during linear accelerations and steady swimming. We separated "steady" and "unsteady" trials and quantified the forward acceleration using inertial measurement units. Compared to steady sequences, unsteady sequences had larger accelerations and higher body amplitudes. The wake consisted of single vortices shed during each tail movement (a '2S' wake). The structure did not change during acceleration, but the circulation of the vortices increased, resulting in larger forces. A fish swimming unsteadily produced significantly more force than the same fish swimming steadily, even when the accelerations were the same. This increase is likely due to increased added mass during unsteady swimming, as a result of the larger body amplitude. Pressure estimates suggest that the increase in force is correlated with more low pressure regions on the anterior body. This work was supported by ARO W911NF-14-1-0494 and NSF RCN-PLS 1062052.

  8. Genotyping-by-sequencing provides the first well-resolved phylogeny for coffee (Coffea) and insights into the evolution of caffeine content in its species: GBS coffee phylogeny and the evolution of caffeine content.

    PubMed

    Hamon, Perla; Grover, Corrinne E; Davis, Aaron P; Rakotomalala, Jean-Jacques; Raharimalala, Nathalie E; Albert, Victor A; Sreenath, Hosahalli L; Stoffelen, Piet; Mitchell, Sharon E; Couturon, Emmanuel; Hamon, Serge; de Kochko, Alexandre; Crouzillat, Dominique; Rigoreau, Michel; Sumirat, Ucu; Akaffou, Sélastique; Guyot, Romain

    2017-04-01

    A comprehensive and meaningful phylogenetic hypothesis for the commercially important coffee genus (Coffea) has long been a key objective for coffee researchers. For molecular studies, progress has been limited by low levels of sequence divergence, leading to insufficient topological resolution and statistical support in phylogenetic trees, particularly for the major lineages and for the numerous species occurring in Madagascar. We report here the first almost fully resolved, broadly sampled phylogenetic hypothesis for coffee, the result of combining genotyping-by-sequencing (GBS) technology with a newly developed, lab-based workflow to integrate short read next-generation sequencing for low numbers of additional samples. Biogeographic patterns indicate either Africa or Asia (or possibly the Arabian Peninsula) as the most likely ancestral locality for the origin of the coffee genus, with independent radiations across Africa, Asia, and the Western Indian Ocean Islands (including Madagascar and Mauritius). The evolution of caffeine, an important trait for commerce and society, was evaluated in light of our phylogeny. High and consistent caffeine content is found only in species from the equatorial, fully humid environments of West and Central Africa, possibly as an adaptive response to increased levels of pest predation. Moderate caffeine production, however, evolved at least one additional time recently (between 2 and 4Mya) in a Madagascan lineage, which suggests that either the biosynthetic pathway was already in place during the early evolutionary history of coffee, or that caffeine synthesis within the genus is subject to convergent evolution, as is also the case for caffeine synthesis in coffee versus tea and chocolate. Copyright © 2017 Elsevier Inc. All rights reserved.

  9. Complete sequences of organelle genomes from the medicinal plant Rhazya stricta (Apocynaceae) and contrasting patterns of mitochondrial genome evolution across asterids.

    PubMed

    Park, Seongjun; Ruhlman, Tracey A; Sabir, Jamal S M; Mutwakil, Mohammed H Z; Baeshen, Mohammed N; Sabir, Meshaal J; Baeshen, Nabih A; Jansen, Robert K

    2014-05-28

    Rhazya stricta is native to arid regions in South Asia and the Middle East and is used extensively in folk medicine to treat a wide range of diseases. In addition to generating genomic resources for this medicinally important plant, analyses of the complete plastid and mitochondrial genomes and a nuclear transcriptome from Rhazya provide insights into inter-compartmental transfers between genomes and the patterns of evolution among eight asterid mitochondrial genomes. The 154,841 bp plastid genome is highly conserved with gene content and order identical to the ancestral organization of angiosperms. The 548,608 bp mitochondrial genome exhibits a number of phenomena including the presence of recombinogenic repeats that generate a multipartite organization, transferred DNA from the plastid and nuclear genomes, and bidirectional DNA transfers between the mitochondrion and the nucleus. The mitochondrial genes sdh3 and rps14 have been transferred to the nucleus and have acquired targeting presequences. In the case of rps14, two copies are present in the nucleus; only one has a mitochondrial targeting presequence and may be functional. Phylogenetic analyses of both nuclear and mitochondrial copies of rps14 across angiosperms suggests Rhazya has experienced a single transfer of this gene to the nucleus, followed by a duplication event. Furthermore, the phylogenetic distribution of gene losses and the high level of sequence divergence in targeting presequences suggest multiple, independent transfers of both sdh3 and rps14 across asterids. Comparative analyses of mitochondrial genomes of eight sequenced asterids indicates a complicated evolutionary history in this large angiosperm clade with considerable diversity in genome organization and size, repeat, gene and intron content, and amount of foreign DNA from the plastid and nuclear genomes. Organelle genomes of Rhazya stricta provide valuable information for improving the understanding of mitochondrial genome evolution

  10. Accelerating Sequences in the Presence of Metal by Exploiting the Spatial Distribution of Off-Resonance

    PubMed Central

    Smith, Matthew R.; Artz, Nathan S.; Koch, Kevin M.; Samsonov, Alexey; Reeder, Scott B.

    2014-01-01

    Purpose To demonstrate feasibility of exploiting the spatial distribution of off-resonance surrounding metallic implants for accelerating multispectral imaging techniques. Theory Multispectral imaging (MSI) techniques perform time-consuming independent 3D acquisitions with varying RF frequency offsets to address the extreme off-resonance from metallic implants. Each off-resonance bin provides a unique spatial sensitivity that is analogous to the sensitivity of a receiver coil, and therefore provides a unique opportunity for acceleration. Methods Fully sampled MSI was performed to demonstrate retrospective acceleration. A uniform sampling pattern across off-resonance bins was compared to several adaptive sampling strategies using a total hip replacement phantom. Monte Carlo simulations were performed to compare noise propagation of two of these strategies. With a total knee replacement phantom, positive and negative off-resonance bins were strategically sampled with respect to the B0 field to minimize aliasing. Reconstructions were performed with a parallel imaging framework to demonstrate retrospective acceleration. Results An adaptive sampling scheme dramatically improved reconstruction quality, which was supported by the noise propagation analysis. Independent acceleration of negative and positive off-resonance bins demonstrated reduced overlapping of aliased signal to improve the reconstruction. Conclusion This work presents the feasibility of acceleration in the presence of metal by exploiting the spatial sensitivities of off-resonance bins. PMID:24431210

  11. Probing the Boundaries of Orthology: The Unanticipated Rapid Evolution of Drosophila centrosomin

    PubMed Central

    Eisman, Robert C.; Kaufman, Thomas C.

    2013-01-01

    The rapid evolution of essential developmental genes and their protein products is both intriguing and problematic. The rapid evolution of gene products with simple protein folds and a lack of well-characterized functional domains typically result in a low discovery rate of orthologous genes. Additionally, in the absence of orthologs it is difficult to study the processes and mechanisms underlying rapid evolution. In this study, we have investigated the rapid evolution of centrosomin (cnn), an essential gene encoding centrosomal protein isoforms required during syncytial development in Drosophila melanogaster. Until recently the rapid divergence of cnn made identification of orthologs difficult and questionable because Cnn violates many of the assumptions underlying models for protein evolution. To overcome these limitations, we have identified a group of insect orthologs and present conserved features likely to be required for the functions attributed to cnn in D. melanogaster. We also show that the rapid divergence of Cnn isoforms is apparently due to frequent coding sequence indels and an accelerated rate of intronic additions and eliminations. These changes appear to be buffered by multi-exon and multi-reading frame maximum potential ORFs, simple protein folds, and the splicing machinery. These buffering features also occur in other genes in Drosophila and may help prevent potentially deleterious mutations due to indels in genes with large coding exons and exon-dense regions separated by small introns. This work promises to be useful for future investigations of cnn and potentially other rapidly evolving genes and proteins. PMID:23749319

  12. Partial sequence homogenization in the 5S multigene families may generate sequence chimeras and spurious results in phylogenetic reconstructions.

    PubMed

    Galián, José A; Rosato, Marcela; Rosselló, Josep A

    2014-03-01

    Multigene families have provided opportunities for evolutionary biologists to assess molecular evolution processes and phylogenetic reconstructions at deep and shallow systematic levels. However, the use of these markers is not free of technical and analytical challenges. Many evolutionary studies that used the nuclear 5S rDNA gene family rarely used contiguous 5S coding sequences due to the routine use of head-to-tail polymerase chain reaction primers that are anchored to the coding region. Moreover, the 5S coding sequences have been concatenated with independent, adjacent gene units in many studies, creating simulated chimeric genes as the raw data for evolutionary analysis. This practice is based on the tacitly assumed, but rarely tested, hypothesis that strict intra-locus concerted evolution processes are operating in 5S rDNA genes, without any empirical evidence as to whether it holds for the recovered data. The potential pitfalls of analysing the patterns of molecular evolution and reconstructing phylogenies based on these chimeric genes have not been assessed to date. Here, we compared the sequence integrity and phylogenetic behavior of entire versus concatenated 5S coding regions from a real data set obtained from closely related plant species (Medicago, Fabaceae). Our results suggest that within arrays sequence homogenization is partially operating in the 5S coding region, which is traditionally assumed to be highly conserved. Consequently, concatenating 5S genes increases haplotype diversity, generating novel chimeric genotypes that most likely do not exist within the genome. In addition, the patterns of gene evolution are distorted, leading to incorrect haplotype relationships in some evolutionary reconstructions.

  13. Comparative analyses of two Geraniaceae transcriptomes using next-generation sequencing

    PubMed Central

    2013-01-01

    Background Organelle genomes of Geraniaceae exhibit several unusual evolutionary phenomena compared to other angiosperm families including accelerated nucleotide substitution rates, widespread gene loss, reduced RNA editing, and extensive genomic rearrangements. Since most organelle-encoded proteins function in multi-subunit complexes that also contain nuclear-encoded proteins, it is likely that the atypical organellar phenomena affect the evolution of nuclear genes encoding organellar proteins. To begin to unravel the complex co-evolutionary interplay between organellar and nuclear genomes in this family, we sequenced nuclear transcriptomes of two species, Geranium maderense and Pelargonium x hortorum. Results Normalized cDNA libraries of G. maderense and P. x hortorum were used for transcriptome sequencing. Five assemblers (MIRA, Newbler, SOAPdenovo, SOAPdenovo-trans [SOAPtrans], Trinity) and two next-generation technologies (454 and Illumina) were compared to determine the optimal transcriptome sequencing approach. Trinity provided the highest quality assembly of Illumina data with the deepest transcriptome coverage. An analysis to determine the amount of sequencing needed for de novo assembly revealed diminishing returns of coverage and quality with data sets larger than sixty million Illumina paired end reads for both species. The G. maderense and P. x hortorum transcriptomes contained fewer transcripts encoding the PLS subclass of PPR proteins relative to other angiosperms, consistent with reduced mitochondrial RNA editing activity in Geraniaceae. In addition, transcripts for all six plastid targeted sigma factors were identified in both transcriptomes, suggesting that one of the highly divergent rpoA-like ORFs in the P. x hortorum plastid genome is functional. Conclusions The findings support the use of the Illumina platform and assemblers optimized for transcriptome assembly, such as Trinity or SOAPtrans, to generate high-quality de novo transcriptomes with

  14. Inversions and inverted transpositions as the basis for an almost universal "format" of genome sequences.

    PubMed

    Albrecht-Buehler, Guenter

    2007-09-01

    In genome duplexes that exceed 100 kb the frequency distributions of their trinucleotides (triplet profiles) are the same in both strands. This remarkable symmetry, sometimes called Chargaff's second parity rule, is not the result of base pairing, but can be explained as the result of countless inversions and inverted transpositions that occurred throughout evolution (G. Albrecht-Buehler, 2006, Proc. Natl. Acad. Sci. USA 103, 17828-17833). Furthermore, comparing the triplet profiles of genomes from a large number of different taxa and species revealed that they were not only strand-symmetrical, but even surprisingly similar to one another (majority profile; G. Albrecht-Buehler, 2007, Genomics 89, 596-601). The present article proposes that the same inversion/transposition mechanism(s) that created the strand symmetry may also explain the existence of the majority profile. Thus they may be key factors in the creation of an almost universal "format" in which genome sequences are written. One may speculate that this universality of genome format may facilitate horizontal gene transfer and, thus, accelerate evolution.

  15. Using reconfigurable hardware to accelerate multiple sequence alignment with ClustalW.

    PubMed

    Oliver, Tim; Schmidt, Bertil; Nathan, Darran; Clemens, Ralf; Maskell, Douglas

    2005-08-15

    Aligning hundreds of sequences using progressive alignment tools such as ClustalW requires several hours on state-of-the-art workstations. We present a new approach to compute multiple sequence alignments in far shorter time using reconfigurable hardware. This results in an implementation of ClustalW with significant runtime savings on a standard off-the-shelf FPGA.

  16. Evidence for Widespread Reticulate Evolution within Human Duplicons

    PubMed Central

    Jackson, Michael S. ; Oliver, Karen ; Loveland, Jane ; Humphray, Sean ; Dunham, Ian ; Rocchi, Mariano ; Viggiano, Luigi ; Park, Jonathan P. ; Hurles, Matthew E. ; Santibanez-Koref, Mauro 

    2005-01-01

    Approximately 5% of the human genome consists of segmental duplications that can cause genomic mutations and may play a role in gene innovation. Reticulate evolutionary processes, such as unequal crossing-over and gene conversion, are known to occur within specific duplicon families, but the broader contribution of these processes to the evolution of human duplications remains poorly characterized. Here, we use phylogenetic profiling to analyze multiple alignments of 24 human duplicon families that span >8 Mb of DNA. Our results indicate that none of them are evolving independently, with all alignments showing sharp discontinuities in phylogenetic signal consistent with reticulation. To analyze these results in more detail, we have developed a quartet method that estimates the relative contribution of nucleotide substitution and reticulate processes to sequence evolution. Our data indicate that most of the duplications show a highly significant excess of sites consistent with reticulate evolution, compared with the number expected by nucleotide substitution alone, with 15 of 30 alignments showing a >20-fold excess over that expected. Using permutation tests, we also show that at least 5% of the total sequence shares 100% sequence identity because of reticulation, a figure that includes 74 independent tracts of perfect identity >2 kb in length. Furthermore, analysis of a subset of alignments indicates that the density of reticulation events is as high as 1 every 4 kb. These results indicate that phylogenetic relationships within recently duplicated human DNA can be rapidly disrupted by reticulate evolution. This finding has important implications for efforts to finish the human genome sequence, complicates comparative sequence analysis of duplicon families, and could profoundly influence the tempo of gene-family evolution. PMID:16252241

  17. Evolution of mixing width induced by general Rayleigh-Taylor instability.

    PubMed

    Zhang, You-Sheng; He, Zhi-Wei; Gao, Fu-Jie; Li, Xin-Liang; Tian, Bao-Lin

    2016-06-01

    Turbulent mixing induced by Rayleigh-Taylor (RT) instability occurs ubiquitously in many natural phenomena and engineering applications. As the simplest and primary descriptor of the mixing process, the evolution of mixing width of the mixing zone plays a notable role in the flows. The flows generally involve complex varying acceleration histories and widely varying density ratios, two dominant factors affecting the evolution of mixing width. However, no satisfactory theory for predicting the evolution has yet been established. Here a theory determining the evolution of mixing width in general RT flows is established to reproduce, first, all of the documented experiments conducted for diverse (i.e., constant, impulsive, oscillating, decreasing, increasing, and complex) acceleration histories and all density ratios. The theory is established in terms of the conservation principle, with special consideration given to the asymmetry of the volume-averaged density fields occurring in actual flows. The results reveal the sensitivity or insensitivity of the evolution of a mixing front of a neighboring light or heavy fluid to the degree of asymmetry and thus explain the distinct evolutions in two experiments with the same configurations.

  18. Overview of the creative genome: effects of genome structure and sequence on the generation of variation and evolution.

    PubMed

    Caporale, Lynn Helena

    2012-09-01

    This overview of a special issue of Annals of the New York Academy of Sciences discusses uneven distribution of distinct types of variation across the genome, the dependence of specific types of variation upon distinct classes of DNA sequences and/or the induction of specific proteins, the circumstances in which distinct variation-generating systems are activated, and the implications of this work for our understanding of evolution and of cancer. Also discussed is the value of non text-based computational methods for analyzing information carried by DNA, early insights into organizational frameworks that affect genome behavior, and implications of this work for comparative genomics. © 2012 New York Academy of Sciences.

  19. The first genome sequences of human bocaviruses from Vietnam

    PubMed Central

    Thanh, Tran Tan; Van, Hoang Minh Tu; Hong, Nguyen Thi Thu; Nhu, Le Nguyen Truc; Anh, Nguyen To; Tuan, Ha Manh; Hien, Ho Van; Tuong, Nguyen Manh; Kien, Trinh Trung; Khanh, Truong Huu; Nhan, Le Nguyen Thanh; Hung, Nguyen Thanh; Chau, Nguyen Van Vinh; Thwaites, Guy; van Doorn, H. Rogier; Tan, Le Van

    2017-01-01

    As part of an ongoing effort to generate complete genome sequences of hand, foot and mouth disease-causing enteroviruses directly from clinical specimens, two complete coding sequences and two partial genomic sequences of human bocavirus 1 (n=3) and 2 (n=1) were co-amplified and sequenced, representing the first genome sequences of human bocaviruses from Vietnam. The sequences may aid future study aiming at understanding the evolution of the virus. PMID:28090592

  20. Rapid genome-wide evolution in Brassica rapa populations following drought revealed by sequencing of ancestral and descendant gene pools.

    PubMed

    Franks, Steven J; Kane, Nolan C; O'Hara, Niamh B; Tittes, Silas; Rest, Joshua S

    2016-08-01

    There is increasing evidence that evolution can occur rapidly in response to selection. Recent advances in sequencing suggest the possibility of documenting genetic changes as they occur in populations, thus uncovering the genetic basis of evolution, particularly if samples are available from both before and after selection. Here, we had a unique opportunity to directly assess genetic changes in natural populations following an evolutionary response to a fluctuation in climate. We analysed genome-wide differences between ancestors and descendants of natural populations of Brassica rapa plants from two locations that rapidly evolved changes in multiple phenotypic traits, including flowering time, following a multiyear late-season drought in California. These ancestor-descendant comparisons revealed evolutionary shifts in allele frequencies in many genes. Some genes showing evolutionary shifts have functions related to drought stress and flowering time, consistent with an adaptive response to selection. Loci differentiated between ancestors and descendants (FST outliers) were generally different from those showing signatures of selection based on site frequency spectrum analysis (Tajima's D), indicating that the loci that evolved in response to the recent drought and those under historical selection were generally distinct. Very few genes showed similar evolutionary responses between two geographically distinct populations, suggesting independent genetic trajectories of evolution yielding parallel phenotypic changes. The results show that selection can result in rapid genome-wide evolutionary shifts in allele frequencies in natural populations, and highlight the usefulness of combining resurrection experiments in natural populations with genomics for studying the genetic basis of adaptive evolution. © 2016 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  1. Biodiversity Meets Neuroscience: From the Sequencing Ship (Ship-Seq) to Deciphering Parallel Evolution of Neural Systems in Omic's Era.

    PubMed

    Moroz, Leonid L

    2015-12-01

    The origins of neural systems and centralized brains are one of the major transitions in evolution. These events might occur more than once over 570-600 million years. The convergent evolution of neural circuits is evident from a diversity of unique adaptive strategies implemented by ctenophores, cnidarians, acoels, molluscs, and basal deuterostomes. But, further integration of biodiversity research and neuroscience is required to decipher critical events leading to development of complex integrative and cognitive functions. Here, we outline reference species and interdisciplinary approaches in reconstructing the evolution of nervous systems. In the "omic" era, it is now possible to establish fully functional genomics laboratories aboard of oceanic ships and perform sequencing and real-time analyses of data at any oceanic location (named here as Ship-Seq). In doing so, fragile, rare, cryptic, and planktonic organisms, or even entire marine ecosystems, are becoming accessible directly to experimental and physiological analyses by modern analytical tools. Thus, we are now in a position to take full advantages from countless "experiments" Nature performed for us in the course of 3.5 billion years of biological evolution. Together with progress in computational and comparative genomics, evolutionary neuroscience, proteomic and developmental biology, a new surprising picture is emerging that reveals many ways of how nervous systems evolved. As a result, this symposium provides a unique opportunity to revisit old questions about the origins of biological complexity. © The Author 2015. Published by Oxford University Press on behalf of the Society for Integrative and Comparative Biology. All rights reserved. For permissions please email: journals.permissions@oup.com.

  2. Moving at the Speed of Potential: A Mixed-Methods Study of Accelerating Developmental Students in a California Community College

    ERIC Educational Resources Information Center

    Parks, Paula L.

    2014-01-01

    Most developmental community college students are not completing the composition sequence successfully. This mixed-methods study examined acceleration as a way to help developmental community college students complete the composition sequence more quickly and more successfully. Acceleration is a curricular redesign that includes challenging…

  3. New solutions with accelerated expansion in string theory

    DOE PAGES

    Dodelson, Matthew; Dong, Xi; Silverstein, Eva; ...

    2014-12-05

    We present concrete solutions with accelerated expansion in string theory, requiring a small, tractable list of stress energy sources. We explain how this construction (and others in progress) evades previous no go theorems for simple accelerating solutions. Our solutions respect an approximate scaling symmetry and realize discrete sequences of values for the equation of state, including one with an accumulation point at w = –1 and another accumulating near w = –1/3 from below. In another class of models, a density of defects generates scaling solutions with accelerated expansion. Here, we briefly discuss potential applications to dark energy phenomenology, andmore » to holography for cosmology.« less

  4. Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution

    PubMed Central

    Kim, Hoon; Zheng, Siyuan; Amini, Seyed S.; Virk, Selene M.; Mikkelsen, Tom; Brat, Daniel J.; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E.; Cohen, Mark L.; Van Meir, Erwin G.; Scarpace, Lisa; Laird, Peter W.; Weinstein, John N.; Lander, Eric S.; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S.

    2015-01-01

    Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. PMID:25650244

  5. Discovery of common sequences absent in the human reference genome using pooled samples from next generation sequencing.

    PubMed

    Liu, Yu; Koyutürk, Mehmet; Maxwell, Sean; Xiang, Min; Veigl, Martina; Cooper, Richard S; Tayo, Bamidele O; Li, Li; LaFramboise, Thomas; Wang, Zhenghe; Zhu, Xiaofeng; Chance, Mark R

    2014-08-16

    Sequences up to several megabases in length have been found to be present in individual genomes but absent in the human reference genome. These sequences may be common in populations, and their absence in the reference genome may indicate rare variants in the genomes of individuals who served as donors for the human genome project. As the reference genome is used in probe design for microarray technology and mapping short reads in next generation sequencing (NGS), this missing sequence could be a source of bias in functional genomic studies and variant analysis. One End Anchor (OEA) and/or orphan reads from paired-end sequencing have been used to identify novel sequences that are absent in reference genome. However, there is no study to investigate the distribution, evolution and functionality of those sequences in human populations. To systematically identify and study the missing common sequences (micSeqs), we extended the previous method by pooling OEA reads from large number of individuals and applying strict filtering methods to remove false sequences. The pipeline was applied to data from phase 1 of the 1000 Genomes Project. We identified 309 micSeqs that are present in at least 1% of the human population, but absent in the reference genome. We confirmed 76% of these 309 micSeqs by comparison to other primate genomes, individual human genomes, and gene expression data. Furthermore, we randomly selected fifteen micSeqs and confirmed their presence using PCR validation in 38 additional individuals. Functional analysis using published RNA-seq and ChIP-seq data showed that eleven micSeqs are highly expressed in human brain and three micSeqs contain transcription factor (TF) binding regions, suggesting they are functional elements. In addition, the identified micSeqs are absent in non-primates and show dynamic acquisition during primate evolution culminating with most micSeqs being present in Africans, suggesting some micSeqs may be important sources of human

  6. Whole-exome sequencing reveals the spectrum of gene mutations and the clonal evolution patterns in paediatric acute myeloid leukaemia.

    PubMed

    Shiba, Norio; Yoshida, Kenichi; Shiraishi, Yuichi; Okuno, Yusuke; Yamato, Genki; Hara, Yusuke; Nagata, Yasunobu; Chiba, Kenichi; Tanaka, Hiroko; Terui, Kiminori; Kato, Motohiro; Park, Myoung-Ja; Ohki, Kentaro; Shimada, Akira; Takita, Junko; Tomizawa, Daisuke; Kudo, Kazuko; Arakawa, Hirokazu; Adachi, Souichi; Taga, Takashi; Tawa, Akio; Ito, Etsuro; Horibe, Keizo; Sanada, Masashi; Miyano, Satoru; Ogawa, Seishi; Hayashi, Yasuhide

    2016-11-01

    Acute myeloid leukaemia (AML) is a molecularly and clinically heterogeneous disease. Targeted sequencing efforts have identified several mutations with diagnostic and prognostic values in KIT, NPM1, CEBPA and FLT3 in both adult and paediatric AML. In addition, massively parallel sequencing enabled the discovery of recurrent mutations (i.e. IDH1/2 and DNMT3A) in adult AML. In this study, whole-exome sequencing (WES) of 22 paediatric AML patients revealed mutations in components of the cohesin complex (RAD21 and SMC3), BCORL1 and ASXL2 in addition to previously known gene mutations. We also revealed intratumoural heterogeneities in many patients, implicating multiple clonal evolution events in the development of AML. Furthermore, targeted deep sequencing in 182 paediatric AML patients identified three major categories of recurrently mutated genes: cohesion complex genes [STAG2, RAD21 and SMC3 in 17 patients (8·3%)], epigenetic regulators [ASXL1/ASXL2 in 17 patients (8·3%), BCOR/BCORL1 in 7 patients (3·4%)] and signalling molecules. We also performed WES in four patients with relapsed AML. Relapsed AML evolved from one of the subclones at the initial phase and was accompanied by many additional mutations, including common driver mutations that were absent or existed only with lower allele frequency in the diagnostic samples, indicating a multistep process causing leukaemia recurrence. © 2016 John Wiley & Sons Ltd.

  7. Mutational robustness accelerates the origin of novel RNA phenotypes through phenotypic plasticity.

    PubMed

    Wagner, Andreas

    2014-02-18

    Novel phenotypes can originate either through mutations in existing genotypes or through phenotypic plasticity, the ability of one genotype to form multiple phenotypes. From molecules to organisms, plasticity is a ubiquitous feature of life, and a potential source of exaptations, adaptive traits that originated for nonadaptive reasons. Another ubiquitous feature is robustness to mutations, although it is unknown whether such robustness helps or hinders the origin of new phenotypes through plasticity. RNA is ideal to address this question, because it shows extensive plasticity in its secondary structure phenotypes, a consequence of their continual folding and unfolding, and these phenotypes have important biological functions. Moreover, RNA is to some extent robust to mutations. This robustness structures RNA genotype space into myriad connected networks of genotypes with the same phenotype, and it influences the dynamics of evolving populations on a genotype network. In this study I show that both effects help accelerate the exploration of novel phenotypes through plasticity. My observations are based on many RNA molecules sampled at random from RNA sequence space, and on 30 biological RNA molecules. They are thus not only a generic feature of RNA sequence space but are relevant for the molecular evolution of biological RNA. Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.

  8. Evolution of multiple quantum coherences with scaled dipolar Hamiltonian

    NASA Astrophysics Data System (ADS)

    Sánchez, Claudia M.; Buljubasich, Lisandro; Pastawski, Horacio M.; Chattah, Ana K.

    2017-08-01

    In this article, we introduce a pulse sequence which allows the monitoring of multiple quantum coherences distribution of correlated spin states developed with scaled dipolar Hamiltonian. The pulse sequence is a modification of our previous Proportionally Refocused Loschmidt echo (PRL echo) with phase increment, in order to verify the accuracy of the weighted coherent quantum dynamics. The experiments were carried out with different scaling factors to analyze the evolution of the total magnetization, the time dependence of the multiple quantum coherence orders, and the development of correlated spins clusters. In all cases, a strong dependence between the evolution rate and the weighting factor is observed. Remarkably, all the curves appeared overlapped in a single trend when plotted against the self-time, a new time scale that includes the scaling factor into the evolution time. In other words, the spin system displayed always the same quantum evolution, slowed down as the scaling factor decreases, confirming the high performance of the new pulse sequence.

  9. Single-cell genomic sequencing using Multiple Displacement Amplification.

    PubMed

    Lasken, Roger S

    2007-10-01

    Single microbial cells can now be sequenced using DNA amplified by the Multiple Displacement Amplification (MDA) reaction. The few femtograms of DNA in a bacterium are amplified into micrograms of high molecular weight DNA suitable for DNA library construction and Sanger sequencing. The MDA-generated DNA also performs well when used directly as template for pyrosequencing by the 454 Life Sciences method. While MDA from single cells loses some of the genomic sequence, this approach will greatly accelerate the pace of sequencing from uncultured microbes. The genetically linked sequences from single cells are also a powerful tool to be used in guiding genomic assembly of shotgun sequences of multiple organisms from environmental DNA extracts (metagenomic sequences).

  10. Biodiversity Meets Neuroscience: From the Sequencing Ship (Ship-Seq) to Deciphering Parallel Evolution of Neural Systems in Omic’s Era

    PubMed Central

    Moroz, Leonid L.

    2015-01-01

    The origins of neural systems and centralized brains are one of the major transitions in evolution. These events might occur more than once over 570–600 million years. The convergent evolution of neural circuits is evident from a diversity of unique adaptive strategies implemented by ctenophores, cnidarians, acoels, molluscs, and basal deuterostomes. But, further integration of biodiversity research and neuroscience is required to decipher critical events leading to development of complex integrative and cognitive functions. Here, we outline reference species and interdisciplinary approaches in reconstructing the evolution of nervous systems. In the “omic” era, it is now possible to establish fully functional genomics laboratories aboard of oceanic ships and perform sequencing and real-time analyses of data at any oceanic location (named here as Ship-Seq). In doing so, fragile, rare, cryptic, and planktonic organisms, or even entire marine ecosystems, are becoming accessible directly to experimental and physiological analyses by modern analytical tools. Thus, we are now in a position to take full advantages from countless “experiments” Nature performed for us in the course of 3.5 billion years of biological evolution. Together with progress in computational and comparative genomics, evolutionary neuroscience, proteomic and developmental biology, a new surprising picture is emerging that reveals many ways of how nervous systems evolved. As a result, this symposium provides a unique opportunity to revisit old questions about the origins of biological complexity. PMID:26163680

  11. Evolution of meiotic recombination genes in maize and teosinte.

    PubMed

    Sidhu, Gaganpreet K; Warzecha, Tomasz; Pawlowski, Wojciech P

    2017-01-25

    Meiotic recombination is a major source of genetic variation in eukaryotes. The role of recombination in evolution is recognized but little is known about how evolutionary forces affect the recombination pathway itself. Although the recombination pathway is fundamentally conserved across different species, genetic variation in recombination components and outcomes has been observed. Theoretical predictions and empirical studies suggest that changes in the recombination pathway are likely to provide adaptive abilities to populations experiencing directional or strong selection pressures, such as those occurring during species domestication. We hypothesized that adaptive changes in recombination may be associated with adaptive evolution patterns of genes involved in meiotic recombination. To examine how maize evolution and domestication affected meiotic recombination genes, we studied patterns of sequence polymorphism and divergence in eleven genes controlling key steps in the meiotic recombination pathway in a diverse set of maize inbred lines and several accessions of teosinte, the wild ancestor of maize. We discovered that, even though the recombination genes generally exhibited high sequence conservation expected in a pathway controlling a key cellular process, they showed substantial levels and diverse patterns of sequence polymorphism. Among others, we found differences in sequence polymorphism patterns between tropical and temperate maize germplasms. Several recombination genes displayed patterns of polymorphism indicative of adaptive evolution. Despite their ancient origin and overall sequence conservation, meiotic recombination genes can exhibit extensive and complex patterns of molecular evolution. Changes in these genes could affect the functioning of the recombination pathway, and may have contributed to the successful domestication of maize and its expansion to new cultivation areas.

  12. Visualizing and Clustering Protein Similarity Networks: Sequences, Structures, and Functions.

    PubMed

    Mai, Te-Lun; Hu, Geng-Ming; Chen, Chi-Ming

    2016-07-01

    Research in the recent decade has demonstrated the usefulness of protein network knowledge in furthering the study of molecular evolution of proteins, understanding the robustness of cells to perturbation, and annotating new protein functions. In this study, we aimed to provide a general clustering approach to visualize the sequence-structure-function relationship of protein networks, and investigate possible causes for inconsistency in the protein classifications based on sequences, structures, and functions. Such visualization of protein networks could facilitate our understanding of the overall relationship among proteins and help researchers comprehend various protein databases. As a demonstration, we clustered 1437 enzymes by their sequences and structures using the minimum span clustering (MSC) method. The general structure of this protein network was delineated at two clustering resolutions, and the second level MSC clustering was found to be highly similar to existing enzyme classifications. The clustering of these enzymes based on sequence, structure, and function information is consistent with each other. For proteases, the Jaccard's similarity coefficient is 0.86 between sequence and function classifications, 0.82 between sequence and structure classifications, and 0.78 between structure and function classifications. From our clustering results, we discussed possible examples of divergent evolution and convergent evolution of enzymes. Our clustering approach provides a panoramic view of the sequence-structure-function network of proteins, helps visualize the relation between related proteins intuitively, and is useful in predicting the structure and function of newly determined protein sequences.

  13. The Causality of Evolution on Different Fitness Landscapes

    NASA Astrophysics Data System (ADS)

    Vyawahare, Saurabh; Austin, Robert; Zhang, Qiucen; Kim, Hyunsung; Bestoso, John

    2013-03-01

    Evolution of antibiotic resistance is a growing problem. One major reason why most antibiotics fail is because of mutations on drug targets (e.g. essential enzymes). Sequencing of clinically resistant isolates have shown that multiple mutational-hotspots exist in coding regions, which could potentially prohibit the binding of drugs. However, it is not clear whether the appearance of each mutation is random or influenced by other factors. In this paper, we compare evolution of resistance to ciprofloxacin from two distinct but well characterized genetic backgrounds. By combining our recently developed evolution reactor and deep whole-genome sequencing, we show different alleles of σs factor lead to fixation of different mutations in gyrA gene that confer ciprofloxacin resistance to bacteria Escherichia coli. Such causality of evolution in different genes provides an opportunity to control the evolution of antibiotic resistance. Sponsored by the NCI/NIH Physical Sciences Oncology Centers

  14. Wind-accelerated orbital evolution in binary systems with giant stars

    NASA Astrophysics Data System (ADS)

    Chen, Zhuo; Blackman, Eric G.; Nordhaus, Jason; Frank, Adam; Carroll-Nellenback, Jonathan

    2018-01-01

    Using 3D radiation-hydrodynamic simulations and analytic theory, we study the orbital evolution of asymptotic giant branch (AGB) binary systems for various initial orbital separations and mass ratios, and thus different initial accretion modes. The time evolution of binary separations and orbital periods are calculated directly from the averaged mass-loss rate, accretion rate and angular momentum loss rate. We separately consider spin-orbit synchronized and zero-spin AGB cases. We find that the angular momentum carried away by the mass loss together with the mass transfer can effectively shrink the orbit when accretion occurs via wind-Roche lobe overflow. In contrast, the larger fraction of mass lost in Bondi-Hoyle-Lyttleton accreting systems acts to enlarge the orbit. Synchronized binaries tend to experience stronger orbital period decay in close binaries. We also find that orbital period decay is faster when we account for the non-linear evolution of the accretion mode as the binary starts to tighten. This can increase the fraction of binaries that result in common envelope, luminous red novae, Type Ia supernovae and planetary nebulae with tight central binaries. The results also imply that planets in the habitable zone around white dwarfs are unlikely to be found.

  15. Next-generation AAV vectors for clinical use: an ever-accelerating race.

    PubMed

    Weinmann, Jonas; Grimm, Dirk

    2017-10-01

    During the past five decades, it has become evident that Adeno-associated virus (AAV) represents one of the most potent, most versatile, and thus most auspicious platforms available for gene delivery into cells, animals and, ultimately, humans. Particularly attractive is the ease with which the viral capsid-the major determinant of virus-host interaction including cell specificity and antibody recognition-can be modified and optimized at will. This has motivated countless researchers to develop high-throughput technologies in which genetically engineered AAV capsid libraries are subjected to a vastly hastened emulation of natural evolution, with the aim to enrich novel synthetic AAV capsids displaying superior features for clinical application. While the power and potential of these forward genetics approaches is undisputed, they are also inherently challenging as success depends on a combination of library quality, fidelity, and complexity. Here, we will describe and discuss two original, very exciting strategies that have emerged over the last three years and that promise to alleviate at least some of these concerns, namely, (i) a reverse genetics approach termed "ancestral AAV sequence reconstruction," and (ii) AAV genome barcoding as a technology that can advance both, forward and reverse genetics stratagems. Notably, despite the conceptual differences of these two technologies, they pursue the same goal which is tailored acceleration of AAV evolution and thus winning the race for the next-generation AAV vectors for clinical use.

  16. Understanding protein evolution: from protein physics to Darwinian selection.

    PubMed

    Zeldovich, Konstantin B; Shakhnovich, Eugene I

    2008-01-01

    Efforts in whole-genome sequencing and structural proteomics start to provide a global view of the protein universe, the set of existing protein structures and sequences. However, approaches based on the selection of individual sequences have not been entirely successful at the quantitative description of the distribution of structures and sequences in the protein universe because evolutionary pressure acts on the entire organism, rather than on a particular molecule. In parallel to this line of study, studies in population genetics and phenomenological molecular evolution established a mathematical framework to describe the changes in genome sequences in populations of organisms over time. Here, we review both microscopic (physics-based) and macroscopic (organism-level) models of protein-sequence evolution and demonstrate that bridging the two scales provides the most complete description of the protein universe starting from clearly defined, testable, and physiologically relevant assumptions.

  17. Genome sequence and rapid evolution of the rice pathogen Xanthomonas oryzae pv. oryzae PXO99A

    PubMed Central

    Salzberg, Steven L; Sommer, Daniel D; Schatz, Michael C; Phillippy, Adam M; Rabinowicz, Pablo D; Tsuge, Seiji; Furutani, Ayako; Ochiai, Hirokazu; Delcher, Arthur L; Kelley, David; Madupu, Ramana; Puiu, Daniela; Radune, Diana; Shumway, Martin; Trapnell, Cole; Aparna, Gudlur; Jha, Gopaljee; Pandey, Alok; Patil, Prabhu B; Ishihara, Hiromichi; Meyer, Damien F; Szurek, Boris; Verdier, Valerie; Koebnik, Ralf; Dow, J Maxwell; Ryan, Robert P; Hirata, Hisae; Tsuyumu, Shinji; Won Lee, Sang; Ronald, Pamela C; Sonti, Ramesh V; Van Sluys, Marie-Anne; Leach, Jan E; White, Frank F; Bogdanove, Adam J

    2008-01-01

    Background Xanthomonas oryzae pv. oryzae causes bacterial blight of rice (Oryza sativa L.), a major disease that constrains production of this staple crop in many parts of the world. We report here on the complete genome sequence of strain PXO99A and its comparison to two previously sequenced strains, KACC10331 and MAFF311018, which are highly similar to one another. Results The PXO99A genome is a single circular chromosome of 5,240,075 bp, considerably longer than the genomes of the other strains (4,941,439 bp and 4,940,217 bp, respectively), and it contains 5083 protein-coding genes, including 87 not found in KACC10331 or MAFF311018. PXO99A contains a greater number of virulence-associated transcription activator-like effector genes and has at least ten major chromosomal rearrangements relative to KACC10331 and MAFF311018. PXO99A contains numerous copies of diverse insertion sequence elements, members of which are associated with 7 out of 10 of the major rearrangements. A rapidly-evolving CRISPR (clustered regularly interspersed short palindromic repeats) region contains evidence of dozens of phage infections unique to the PXO99A lineage. PXO99A also contains a unique, near-perfect tandem repeat of 212 kilobases close to the replication terminus. Conclusion Our results provide striking evidence of genome plasticity and rapid evolution within Xanthomonas oryzae pv. oryzae. The comparisons point to sources of genomic variation and candidates for strain-specific adaptations of this pathogen that help to explain the extraordinary diversity of Xanthomonas oryzae pv. oryzae genotypes and races that have been isolated from around the world. PMID:18452608

  18. Combining experimental evolution with next-generation sequencing: a powerful tool to study adaptation from standing genetic variation.

    PubMed

    Schlötterer, C; Kofler, R; Versace, E; Tobler, R; Franssen, S U

    2015-05-01

    Evolve and resequence (E&R) is a new approach to investigate the genomic responses to selection during experimental evolution. By using whole genome sequencing of pools of individuals (Pool-Seq), this method can identify selected variants in controlled and replicable experimental settings. Reviewing the current state of the field, we show that E&R can be powerful enough to identify causative genes and possibly even single-nucleotide polymorphisms. We also discuss how the experimental design and the complexity of the trait could result in a large number of false positive candidates. We suggest experimental and analytical strategies to maximize the power of E&R to uncover the genotype-phenotype link and serve as an important research tool for a broad range of evolutionary questions.

  19. A particle accelerator employing transient space charge potentials

    DOEpatents

    Post, R.F.

    1988-02-25

    The invention provides an accelerator for ions and charged particles. The plasma is generated and confined in a magnetic mirror field. The electrons of the plasma are heated to high temperatures. A series of local coils are placed along the axis of the magnetic mirror field. As an ion or particle beam is directed along the axis in sequence the coils are rapidly pulsed creating a space charge to accelerate and focus the beam of ions or charged particles. 3 figs.

  20. Dynamic Evolution of the Chloroplast Genome in the Green Algal Classes Pedinophyceae and Trebouxiophyceae.

    PubMed

    Turmel, Monique; Otis, Christian; Lemieux, Claude

    2015-07-01

    Previous studies of trebouxiophycean chloroplast genomes revealed little information regarding the evolutionary dynamics of this genome because taxon sampling was too sparse and the relationships between the sampled taxa were unknown. We recently sequenced the chloroplast genomes of 27 trebouxiophycean and 2 pedinophycean green algae to resolve the relationships among the main lineages recognized for the Trebouxiophyceae. These taxa and the previously sampled members of the Pedinophyceae and Trebouxiophyceae are included in the comparative chloroplast genome analysis we report here. The 38 genomes examined display considerable variability at all levels, except gene content. Our results highlight the high propensity of the rDNA-containing large inverted repeat (IR) to vary in size, gene content and gene order as well as the repeated losses it experienced during trebouxiophycean evolution. Of the seven predicted IR losses, one event demarcates a superclade of 11 taxa representing 5 late-diverging lineages. IR expansions/contractions account not only for changes in gene content in this region but also for changes in gene order and gene duplications. Inversions also led to gene rearrangements within the IR, including the reversal or disruption of the rDNA operon in some lineages. Most of the 20 IR-less genomes are more rearranged compared with their IR-containing homologs and tend to show an accelerated rate of sequence evolution. In the IR-less superclade, several ancestral operons were disrupted, a few genes were fragmented, and a subgroup of taxa features a G+C-biased nucleotide composition. Our analyses also unveiled putative cases of gene acquisitions through horizontal transfer. © The Author(s) 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  1. Evolution of biological complexity

    PubMed Central

    Adami, Christoph; Ofria, Charles; Collier, Travis C.

    2000-01-01

    To make a case for or against a trend in the evolution of complexity in biological evolution, complexity needs to be both rigorously defined and measurable. A recent information-theoretic (but intuitively evident) definition identifies genomic complexity with the amount of information a sequence stores about its environment. We investigate the evolution of genomic complexity in populations of digital organisms and monitor in detail the evolutionary transitions that increase complexity. We show that, because natural selection forces genomes to behave as a natural “Maxwell Demon,” within a fixed environment, genomic complexity is forced to increase. PMID:10781045

  2. BarraCUDA - a fast short read sequence aligner using graphics processing units

    PubMed Central

    2012-01-01

    Background With the maturation of next-generation DNA sequencing (NGS) technologies, the throughput of DNA sequencing reads has soared to over 600 gigabases from a single instrument run. General purpose computing on graphics processing units (GPGPU), extracts the computing power from hundreds of parallel stream processors within graphics processing cores and provides a cost-effective and energy efficient alternative to traditional high-performance computing (HPC) clusters. In this article, we describe the implementation of BarraCUDA, a GPGPU sequence alignment software that is based on BWA, to accelerate the alignment of sequencing reads generated by these instruments to a reference DNA sequence. Findings Using the NVIDIA Compute Unified Device Architecture (CUDA) software development environment, we ported the most computational-intensive alignment component of BWA to GPU to take advantage of the massive parallelism. As a result, BarraCUDA offers a magnitude of performance boost in alignment throughput when compared to a CPU core while delivering the same level of alignment fidelity. The software is also capable of supporting multiple CUDA devices in parallel to further accelerate the alignment throughput. Conclusions BarraCUDA is designed to take advantage of the parallelism of GPU to accelerate the alignment of millions of sequencing reads generated by NGS instruments. By doing this, we could, at least in part streamline the current bioinformatics pipeline such that the wider scientific community could benefit from the sequencing technology. BarraCUDA is currently available from http://seqbarracuda.sf.net PMID:22244497

  3. Recalibrating Equus evolution using the genome sequence of an early Middle Pleistocene horse.

    PubMed

    Orlando, Ludovic; Ginolhac, Aurélien; Zhang, Guojie; Froese, Duane; Albrechtsen, Anders; Stiller, Mathias; Schubert, Mikkel; Cappellini, Enrico; Petersen, Bent; Moltke, Ida; Johnson, Philip L F; Fumagalli, Matteo; Vilstrup, Julia T; Raghavan, Maanasa; Korneliussen, Thorfinn; Malaspinas, Anna-Sapfo; Vogt, Josef; Szklarczyk, Damian; Kelstrup, Christian D; Vinther, Jakob; Dolocan, Andrei; Stenderup, Jesper; Velazquez, Amhed M V; Cahill, James; Rasmussen, Morten; Wang, Xiaoli; Min, Jiumeng; Zazula, Grant D; Seguin-Orlando, Andaine; Mortensen, Cecilie; Magnussen, Kim; Thompson, John F; Weinstock, Jacobo; Gregersen, Kristian; Røed, Knut H; Eisenmann, Véra; Rubin, Carl J; Miller, Donald C; Antczak, Douglas F; Bertelsen, Mads F; Brunak, Søren; Al-Rasheid, Khaled A S; Ryder, Oliver; Andersson, Leif; Mundy, John; Krogh, Anders; Gilbert, M Thomas P; Kjær, Kurt; Sicheritz-Ponten, Thomas; Jensen, Lars Juhl; Olsen, Jesper V; Hofreiter, Michael; Nielsen, Rasmus; Shapiro, Beth; Wang, Jun; Willerslev, Eske

    2013-07-04

    The rich fossil record of equids has made them a model for evolutionary processes. Here we present a 1.12-times coverage draft genome from a horse bone recovered from permafrost dated to approximately 560-780 thousand years before present (kyr BP). Our data represent the oldest full genome sequence determined so far by almost an order of magnitude. For comparison, we sequenced the genome of a Late Pleistocene horse (43 kyr BP), and modern genomes of five domestic horse breeds (Equus ferus caballus), a Przewalski's horse (E. f. przewalskii) and a donkey (E. asinus). Our analyses suggest that the Equus lineage giving rise to all contemporary horses, zebras and donkeys originated 4.0-4.5 million years before present (Myr BP), twice the conventionally accepted time to the most recent common ancestor of the genus Equus. We also find that horse population size fluctuated multiple times over the past 2 Myr, particularly during periods of severe climatic changes. We estimate that the Przewalski's and domestic horse populations diverged 38-72 kyr BP, and find no evidence of recent admixture between the domestic horse breeds and the Przewalski's horse investigated. This supports the contention that Przewalski's horses represent the last surviving wild horse population. We find similar levels of genetic variation among Przewalski's and domestic populations, indicating that the former are genetically viable and worthy of conservation efforts. We also find evidence for continuous selection on the immune system and olfaction throughout horse evolution. Finally, we identify 29 genomic regions among horse breeds that deviate from neutrality and show low levels of genetic variation compared to the Przewalski's horse. Such regions could correspond to loci selected early during domestication.

  4. Evolution of biological sequences implies an extreme value distribution of type I for both global and local pairwise alignment scores.

    PubMed

    Bastien, Olivier; Maréchal, Eric

    2008-08-07

    Confidence in pairwise alignments of biological sequences, obtained by various methods such as Blast or Smith-Waterman, is critical for automatic analyses of genomic data. Two statistical models have been proposed. In the asymptotic limit of long sequences, the Karlin-Altschul model is based on the computation of a P-value, assuming that the number of high scoring matching regions above a threshold is Poisson distributed. Alternatively, the Lipman-Pearson model is based on the computation of a Z-value from a random score distribution obtained by a Monte-Carlo simulation. Z-values allow the deduction of an upper bound of the P-value (1/Z-value2) following the TULIP theorem. Simulations of Z-value distribution is known to fit with a Gumbel law. This remarkable property was not demonstrated and had no obvious biological support. We built a model of evolution of sequences based on aging, as meant in Reliability Theory, using the fact that the amount of information shared between an initial sequence and the sequences in its lineage (i.e., mutual information in Information Theory) is a decreasing function of time. This quantity is simply measured by a sequence alignment score. In systems aging, the failure rate is related to the systems longevity. The system can be a machine with structured components, or a living entity or population. "Reliability" refers to the ability to operate properly according to a standard. Here, the "reliability" of a sequence refers to the ability to conserve a sufficient functional level at the folded and maturated protein level (positive selection pressure). Homologous sequences were considered as systems 1) having a high redundancy of information reflected by the magnitude of their alignment scores, 2) which components are the amino acids that can independently be damaged by random DNA mutations. From these assumptions, we deduced that information shared at each amino acid position evolved with a constant rate, corresponding to the

  5. Pyvolve: A Flexible Python Module for Simulating Sequences along Phylogenies.

    PubMed

    Spielman, Stephanie J; Wilke, Claus O

    2015-01-01

    We introduce Pyvolve, a flexible Python module for simulating genetic data along a phylogeny using continuous-time Markov models of sequence evolution. Easily incorporated into Python bioinformatics pipelines, Pyvolve can simulate sequences according to most standard models of nucleotide, amino-acid, and codon sequence evolution. All model parameters are fully customizable. Users can additionally specify custom evolutionary models, with custom rate matrices and/or states to evolve. This flexibility makes Pyvolve a convenient framework not only for simulating sequences under a wide variety of conditions, but also for developing and testing new evolutionary models. Pyvolve is an open-source project under a FreeBSD license, and it is available for download, along with a detailed user-manual and example scripts, from http://github.com/sjspielman/pyvolve.

  6. The great escape - III. Placing post-main-sequence evolution of planetary and binary systems in a Galactic context

    NASA Astrophysics Data System (ADS)

    Veras, Dimitri; Evans, N. Wyn; Wyatt, Mark C.; Tout, Christopher A.

    2014-01-01

    Our improving understanding of the life cycle of planetary systems prompts investigations of the role of the Galenvironment before, during and after asymptotic giant branch (AGB) stellar evolution. Here, we investigate the interplay between stellar mass-loss, Galactic tidal perturbations and stellar flybys for evolving stars which host one planet, smaller body or stellar binary companion and reside in the Milky Way's bulge or disc. We find that the potential evolutionary pathways from a main sequence (MS) to a white dwarf (WD) planetary system are a strong function of Galactocentric distance only with respect to the prevalence of stellar flybys. Planetary ejection and collision with the parent star should be more common towards the bulge. At a given location anywhere in the Galaxy, if the mass-loss is adiabatic, then the secondary is likely to avoid close flybys during AGB evolution, and cannot eventually escape the resulting WD because of Galactic tides alone. Partly because AGB mass-loss will shrink a planetary system's Hill ellipsoid axes by about 20 to 40 per cent, Oort clouds orbiting WDs are likely to be more depleted and dynamically excited than on the MS.

  7. Lagrangian acceleration statistics in a turbulent channel flow

    NASA Astrophysics Data System (ADS)

    Stelzenmuller, Nickolas; Polanco, Juan Ignacio; Vignal, Laure; Vinkovic, Ivana; Mordant, Nicolas

    2017-05-01

    Lagrangian acceleration statistics in a fully developed turbulent channel flow at Reτ=1440 are investigated, based on tracer particle tracking in experiments and direct numerical simulations. The evolution with wall distance of the Lagrangian velocity and acceleration time scales is analyzed. Dependency between acceleration components in the near-wall region is described using cross-correlations and joint probability density functions. The strong streamwise coherent vortices typical of wall-bounded turbulent flows are shown to have a significant impact on the dynamics. This results in a strong anisotropy at small scales in the near-wall region that remains present in most of the channel. Such statistical properties may be used as constraints in building advanced Lagrangian stochastic models to predict the dispersion and mixing of chemical components for combustion or environmental studies.

  8. Correlation between evolution of inclusions and pitting corrosion in 304 stainless steel with yttrium addition.

    PubMed

    Shi, Weining; Yang, Shufeng; Li, Jingshe

    2018-03-19

    Effects of the evolution of inclusions on the pitting corrosion resistance of 304 stainless steel with different contents of the rare-earth element yttrium (Y) were studied using thermodynamic calculations, accelerated immersion tests, and electrochemical measurements. The experimental results showed that regular Y 2 O 3 inclusions demonstrated the best pitting resistance, followed in sequence by (Al,Mn)O inclusions, the composite inclusions, and irregular Y 2 O 3 inclusions. The pitting resistance first decreased, then increased, and then decreased again with increasing Y content, because sulfide inclusions were easily generated when the Y content was low and YN inclusions were easily generated at higher Y contents. The best pitting corrosion resistance was obtained for 304 stainless steel with addition of 0.019% Y.

  9. Towards resolving Lamiales relationships: insights from rapidly evolving chloroplast sequences

    PubMed Central

    2010-01-01

    Background In the large angiosperm order Lamiales, a diverse array of highly specialized life strategies such as carnivory, parasitism, epiphytism, and desiccation tolerance occur, and some lineages possess drastically accelerated DNA substitutional rates or miniaturized genomes. However, understanding the evolution of these phenomena in the order, and clarifying borders of and relationships among lamialean families, has been hindered by largely unresolved trees in the past. Results Our analysis of the rapidly evolving trnK/matK, trnL-F and rps16 chloroplast regions enabled us to infer more precise phylogenetic hypotheses for the Lamiales. Relationships among the nine first-branching families in the Lamiales tree are now resolved with very strong support. Subsequent to Plocospermataceae, a clade consisting of Carlemanniaceae plus Oleaceae branches, followed by Tetrachondraceae and a newly inferred clade composed of Gesneriaceae plus Calceolariaceae, which is also supported by morphological characters. Plantaginaceae (incl. Gratioleae) and Scrophulariaceae are well separated in the backbone grade; Lamiaceae and Verbenaceae appear in distant clades, while the recently described Linderniaceae are confirmed to be monophyletic and in an isolated position. Conclusions Confidence about deep nodes of the Lamiales tree is an important step towards understanding the evolutionary diversification of a major clade of flowering plants. The degree of resolution obtained here now provides a first opportunity to discuss the evolution of morphological and biochemical traits in Lamiales. The multiple independent evolution of the carnivorous syndrome, once in Lentibulariaceae and a second time in Byblidaceae, is strongly supported by all analyses and topological tests. The evolution of selected morphological characters such as flower symmetry is discussed. The addition of further sequence data from introns and spacers holds promise to eventually obtain a fully resolved plastid tree of

  10. A Model of Substitution Trajectories in Sequence Space and Long-Term Protein Evolution

    PubMed Central

    Usmanova, Dinara R.; Ferretti, Luca; Povolotskaya, Inna S.; Vlasov, Peter K.; Kondrashov, Fyodor A.

    2015-01-01

    The nature of factors governing the tempo and mode of protein evolution is a fundamental issue in evolutionary biology. Specifically, whether or not interactions between different sites, or epistasis, are important in directing the course of evolution became one of the central questions. Several recent reports have scrutinized patterns of long-term protein evolution claiming them to be compatible only with an epistatic fitness landscape. However, these claims have not yet been substantiated with a formal model of protein evolution. Here, we formulate a simple covarion-like model of protein evolution focusing on the rate at which the fitness impact of amino acids at a site changes with time. We then apply the model to the data on convergent and divergent protein evolution to test whether or not the incorporation of epistatic interactions is necessary to explain the data. We find that convergent evolution cannot be explained without the incorporation of epistasis and the rate at which an amino acid state switches from being acceptable at a site to being deleterious is faster than the rate of amino acid substitution. Specifically, for proteins that have persisted in modern prokaryotic organisms since the last universal common ancestor for one amino acid substitution approximately ten amino acid states switch from being accessible to being deleterious, or vice versa. Thus, molecular evolution can only be perceived in the context of rapid turnover of which amino acids are available for evolution. PMID:25415964

  11. Adaptive microclimatic evolution of the dehydrin 6 gene in wild barley at "Evolution Canyon", Israel.

    PubMed

    Yang, Zujun; Zhang, Tao; Li, Guangrong; Nevo, Eviatar

    2011-12-01

    Dehydrins are one of the major stress-induced gene families, and the expression of dehydrin 6 (Dhn6) is strictly related to drought in barley. In order to investigate how the evolution of the Dhn6 gene is associated with adaptation to environmental changes, we examined 48 genotypes of wild barley, Hordeum spontaneum, from "Evolution Canyon" at Mount Carmel, Israel. The Dhn6 sequences of the 48 genotypes were identified, and a recent insertion of 342 bp at 5'UTR was found in the sequences of 11 genotypes. Both nucleotide and haplotype diversity of single nucleotide polymorphism in Dhn6 coding regions were higher on the AS ("African" slope or dry slope) than on the ES ("European" slope or humid slope), and the applied Tajima D and Fu-Li test rejected neutrality of SNP diversity. Expression analysis indicated that the 342 bp insertion at 5'UTR was associated with the earlier up-regulation of Dhn6 after dehydration. The genetic divergence of amino acids sequences indicated significant positive selection of Dhn6 among the wild barley populations. The diversity of Dhn6 in microclimatic divergence slopes suggested that Dhn6 has been subjected to natural selection and adaptively associated with drought resistance of wild barley at "Evolution Canyon".

  12. Genome Evolution and Meiotic Maps by Massively Parallel DNA Sequencing: Spotted Gar, an Outgroup for the Teleost Genome Duplication

    PubMed Central

    Amores, Angel; Catchen, Julian; Ferrara, Allyse; Fontenot, Quenton; Postlethwait, John H.

    2011-01-01

    Genomic resources for hundreds of species of evolutionary, agricultural, economic, and medical importance are unavailable due to the expense of well-assembled genome sequences and difficulties with multigenerational studies. Teleost fish provide many models for human disease but possess anciently duplicated genomes that sometimes obfuscate connectivity. Genomic information representing a fish lineage that diverged before the teleost genome duplication (TGD) would provide an outgroup for exploring the mechanisms of evolution after whole-genome duplication. We exploited massively parallel DNA sequencing to develop meiotic maps with thrift and speed by genotyping F1 offspring of a single female and a single male spotted gar (Lepisosteus oculatus) collected directly from nature utilizing only polymorphisms existing in these two wild individuals. Using Stacks, software that automates the calling of genotypes from polymorphisms assayed by Illumina sequencing, we constructed a map containing 8406 markers. RNA-seq on two map-cross larvae provided a reference transcriptome that identified nearly 1000 mapped protein-coding markers and allowed genome-wide analysis of conserved synteny. Results showed that the gar lineage diverged from teleosts before the TGD and its genome is organized more similarly to that of humans than teleosts. Thus, spotted gar provides a critical link between medical models in teleost fish, to which gar is biologically similar, and humans, to which gar is genomically similar. Application of our F1 dense mapping strategy to species with no prior genome information promises to facilitate comparative genomics and provide a scaffold for ordering the numerous contigs arising from next generation genome sequencing. PMID:21828280

  13. The evolution of galaxies

    NASA Technical Reports Server (NTRS)

    Gunn, J. E.

    1982-01-01

    The recent observational evidence on the evolution of galaxies is reviewed and related to the framework of current ideas for galaxy formation from primordial density fluctuations. Recent strong evidence for the evolution of the stellar population in ellipticals is presented, as well as evidence that not all ellipticals behave as predicted by any simple theory. The status of counts of faint galaxies and the implications for the evolution of spirals is discussed, together with a discussion of recent work on the redshift distribution of galaxies at faint magnitudes and a spectroscopic investigation of the Butcher-Oemler blue cluster galaxies. Finally a new picture for the formation and evolution of disk galaxies which may explain most of the features of the Hubble sequence is outlined.

  14. Sexual selection expedites the evolution of pesticide resistance.

    PubMed

    Jacomb, Frances; Marsh, Jason; Holman, Luke

    2016-12-01

    The evolution of insecticide resistance by crop pests and disease vectors causes serious problems for agriculture and health. Sexual selection can accelerate or hinder adaptation to abiotic challenges in a variety of ways, but the effect of sexual selection on resistance evolution is little studied. Here, we examine this question using experimental evolution in the pest insect Tribolium castaneum. The experimental removal of sexual selection slowed the evolution of resistance in populations treated with pyrethroid pesticide, and also reduced the rate at which resistance was lost from pesticide-free populations. These results suggest that selection arising from variance in mating and fertilization success can augment natural selection on pesticide resistance, meaning that sexual selection should be considered when designing strategies to limit the evolution of pesticide resistance. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

  15. Adaptive Evolution and Divergence of SERPINB3: A Young Duplicate in Great Apes

    PubMed Central

    Gomes, Sílvia; Marques, Patrícia I.; Matthiesen, Rune; Seixas, Susana

    2014-01-01

    A series of duplication events led to an expansion of clade B Serine Protease Inhibitors (SERPIN), currently displaying a large repertoire of functions in vertebrates. Accordingly, the recent duplicates SERPINB3 and B4 located in human 18q21.3 SERPIN cluster control the activity of different cysteine and serine proteases, respectively. Here, we aim to assess SERPINB3 and B4 coevolution with their target proteases in order to understand the evolutionary forces shaping the accelerated divergence of these duplicates. Phylogenetic analysis of primate sequences placed the duplication event in a Hominoidae ancestor (∼30 Mya) and the emergence of SERPINB3 in Homininae (∼9 Mya). We detected evidence of strong positive selection throughout SERPINB4/B3 primate tree and target proteases, cathepsin L2 (CTSL2) and G (CTSG) and chymase (CMA1). Specifically, in the Homininae clade a perfect match was observed between the adaptive evolution of SERPINB3 and cathepsin S (CTSS) and most of sites under positive selection were located at the inhibitor/protease interface. Altogether our results seem to favour a coevolution hypothesis for SERPINB3, CTSS and CTSL2 and for SERPINB4 and CTSG and CMA1. A scenario of an accelerated evolution driven by host-pathogen interactions is also possible since SERPINB3/B4 are potent inhibitors of exogenous proteases, released by infectious agents. Finally, similar patterns of expression and the sharing of many regulatory motifs suggest neofunctionalization as the best fitted model of the functional divergence of SERPINB3 and B4 duplicates. PMID:25133778

  16. Seeing chordate evolution through the Ciona genome sequence

    PubMed Central

    Cañestro, Cristian; Bassham, Susan; Postlethwait, John H

    2003-01-01

    A draft sequence of the compact genome of the sea squirt Ciona intestinalis, a non-vertebrate chordate that diverged very early from other chordates, including vertebrates, illuminates how chordates originated and how vertebrate developmental innovations evolved. PMID:12620098

  17. Mechanistically Distinct Pathways of Divergent Regulatory DNA Creation Contribute to Evolution of Human-Specific Genomic Regulatory Networks Driving Phenotypic Divergence of Homo sapiens.

    PubMed

    Glinsky, Gennadi V

    2016-09-19

    Thousands of candidate human-specific regulatory sequences (HSRS) have been identified, supporting the hypothesis that unique to human phenotypes result from human-specific alterations of genomic regulatory networks. Collectively, a compendium of multiple diverse families of HSRS that are functionally and structurally divergent from Great Apes could be defined as the backbone of human-specific genomic regulatory networks. Here, the conservation patterns analysis of 18,364 candidate HSRS was carried out requiring that 100% of bases must remap during the alignments of human, chimpanzee, and bonobo sequences. A total of 5,535 candidate HSRS were identified that are: (i) highly conserved in Great Apes; (ii) evolved by the exaptation of highly conserved ancestral DNA; (iii) defined by either the acceleration of mutation rates on the human lineage or the functional divergence from non-human primates. The exaptation of highly conserved ancestral DNA pathway seems mechanistically distinct from the evolution of regulatory DNA segments driven by the species-specific expansion of transposable elements. Genome-wide proximity placement analysis of HSRS revealed that a small fraction of topologically associating domains (TADs) contain more than half of HSRS from four distinct families. TADs that are enriched for HSRS and termed rapidly evolving in humans TADs (revTADs) comprise 0.8-10.3% of 3,127 TADs in the hESC genome. RevTADs manifest distinct correlation patterns between placements of human accelerated regions, human-specific transcription factor-binding sites, and recombination rates. There is a significant enrichment within revTAD boundaries of hESC-enhancers, primate-specific CTCF-binding sites, human-specific RNAPII-binding sites, hCONDELs, and H3K4me3 peaks with human-specific enrichment at TSS in prefrontal cortex neurons (P < 0.0001 in all instances). Present analysis supports the idea that phenotypic divergence of Homo sapiens is driven by the evolution of human

  18. 160-fold acceleration of the Smith-Waterman algorithm using a field programmable gate array (FPGA)

    PubMed Central

    Li, Isaac TS; Shum, Warren; Truong, Kevin

    2007-01-01

    Background To infer homology and subsequently gene function, the Smith-Waterman (SW) algorithm is used to find the optimal local alignment between two sequences. When searching sequence databases that may contain hundreds of millions of sequences, this algorithm becomes computationally expensive. Results In this paper, we focused on accelerating the Smith-Waterman algorithm by using FPGA-based hardware that implemented a module for computing the score of a single cell of the SW matrix. Then using a grid of this module, the entire SW matrix was computed at the speed of field propagation through the FPGA circuit. These modifications dramatically accelerated the algorithm's computation time by up to 160 folds compared to a pure software implementation running on the same FPGA with an Altera Nios II softprocessor. Conclusion This design of FPGA accelerated hardware offers a new promising direction to seeking computation improvement of genomic database searching. PMID:17555593

  19. 160-fold acceleration of the Smith-Waterman algorithm using a field programmable gate array (FPGA).

    PubMed

    Li, Isaac T S; Shum, Warren; Truong, Kevin

    2007-06-07

    To infer homology and subsequently gene function, the Smith-Waterman (SW) algorithm is used to find the optimal local alignment between two sequences. When searching sequence databases that may contain hundreds of millions of sequences, this algorithm becomes computationally expensive. In this paper, we focused on accelerating the Smith-Waterman algorithm by using FPGA-based hardware that implemented a module for computing the score of a single cell of the SW matrix. Then using a grid of this module, the entire SW matrix was computed at the speed of field propagation through the FPGA circuit. These modifications dramatically accelerated the algorithm's computation time by up to 160 folds compared to a pure software implementation running on the same FPGA with an Altera Nios II softprocessor. This design of FPGA accelerated hardware offers a new promising direction to seeking computation improvement of genomic database searching.

  20. Functionally conserved enhancers with divergent sequences in distant vertebrates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Song; Oksenberg, Nir; Takayama, Sachiko

    To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. In conclusion, our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species.

  1. Functionally conserved enhancers with divergent sequences in distant vertebrates

    DOE PAGES

    Yang, Song; Oksenberg, Nir; Takayama, Sachiko; ...

    2015-10-30

    To examine the contributions of sequence and function conservation in the evolution of enhancers, we systematically identified enhancers whose sequences are not conserved among distant groups of vertebrate species, but have homologous function and are likely to be derived from a common ancestral sequence. In conclusion, our approach combined comparative genomics and epigenomics to identify potential enhancer sequences in the genomes of three groups of distantly related vertebrate species.

  2. New perspectives on bacterial ferredoxin evolution

    NASA Technical Reports Server (NTRS)

    George, D. G.; Hunt, L. T.; Yeh, L.-S. L.; Barker, W. C.

    1985-01-01

    Ferredoxins are low-molecular-weight, nonheme, iron proteins which function as electron carriers in a wide variety of electron transport chains. Howard et al. (1983) have suggested that the amino end of Azotobacter vinelandii ferredoxin shows a greater similarity to the carboxyl end of ferredoxin from Chromatium vinosum and that their half-chain sequences are homologous when the half-chains of either species are considered in inverse order. Examination of this proposition has made it necessary to reevaluate previous conclusions concerning the evolution of bacterial ferredoxin. Attention is given to the properties of the bacterial ferredoxin sequences, and the evolution of the bacterial ferredoxins.

  3. Tuning Spatial Profiles of Selection Pressure to Modulate the Evolution of Drug Resistance

    NASA Astrophysics Data System (ADS)

    De Jong, Maxwell G.; Wood, Kevin B.

    2018-06-01

    Spatial heterogeneity plays an important role in the evolution of drug resistance. While recent studies have indicated that spatial gradients of selection pressure can accelerate resistance evolution, much less is known about evolution in more complex spatial profiles. Here we use a stochastic toy model of drug resistance to investigate how different spatial profiles of selection pressure impact the time to fixation of a resistant allele. Using mean first passage time calculations, we show that spatial heterogeneity accelerates resistance evolution when the rate of spatial migration is sufficiently large relative to mutation but slows fixation for small migration rates. Interestingly, there exists an intermediate regime—characterized by comparable rates of migration and mutation—in which the rate of fixation can be either accelerated or decelerated depending on the spatial profile, even when spatially averaged selection pressure remains constant. Finally, we demonstrate that optimal tuning of the spatial profile can dramatically slow the spread and fixation of resistant subpopulations, even in the absence of a fitness cost for resistance. Our results may lay the groundwork for optimized, spatially resolved drug dosing strategies for mitigating the effects of drug resistance.

  4. Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality

    PubMed Central

    Wei, Chaoling; Yang, Hua; Wang, Songbo; Zhao, Jian; Liu, Chun; Gao, Liping; Xia, Enhua; Lu, Ying; Tai, Yuling; She, Guangbiao; Sun, Jun; Cao, Haisheng; Tong, Wei; Gao, Qiang; Li, Yeyun; Deng, Weiwei; Jiang, Xiaolan; Wang, Wenzhao; Chen, Qi; Zhang, Shihua; Li, Haijing; Wu, Junlan; Wang, Ping; Li, Penghui; Shi, Chengying; Zheng, Fengya; Jian, Jianbo; Huang, Bei; Shan, Dai; Shi, Mingming; Fang, Congbing; Yue, Yi; Li, Fangdong; Li, Daxiang; Wei, Shu; Han, Bin; Jiang, Changjun; Yin, Ye; Xia, Tao; Zhang, Zhengzhu; Bennetzen, Jeffrey L.; Zhao, Shancen; Wan, Xiaochun

    2018-01-01

    Tea, one of the world’s most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to ∼0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred ∼30 to 40 and ∼90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties. PMID:29678829

  5. Position specific variation in the rate of evolution in transcription factor binding sites

    PubMed Central

    Moses, Alan M; Chiang, Derek Y; Kellis, Manolis; Lander, Eric S; Eisen, Michael B

    2003-01-01

    Background The binding sites of sequence specific transcription factors are an important and relatively well-understood class of functional non-coding DNAs. Although a wide variety of experimental and computational methods have been developed to characterize transcription factor binding sites, they remain difficult to identify. Comparison of non-coding DNA from related species has shown considerable promise in identifying these functional non-coding sequences, even though relatively little is known about their evolution. Results Here we analyse the genome sequences of the budding yeasts Saccharomyces cerevisiae, S. bayanus, S. paradoxus and S. mikatae to study the evolution of transcription factor binding sites. As expected, we find that both experimentally characterized and computationally predicted binding sites evolve slower than surrounding sequence, consistent with the hypothesis that they are under purifying selection. We also observe position-specific variation in the rate of evolution within binding sites. We find that the position-specific rate of evolution is positively correlated with degeneracy among binding sites within S. cerevisiae. We test theoretical predictions for the rate of evolution at positions where the base frequencies deviate from background due to purifying selection and find reasonable agreement with the observed rates of evolution. Finally, we show how the evolutionary characteristics of real binding motifs can be used to distinguish them from artefacts of computational motif finding algorithms. Conclusion As has been observed for protein sequences, the rate of evolution in transcription factor binding sites varies with position, suggesting that some regions are under stronger functional constraint than others. This variation likely reflects the varying importance of different positions in the formation of the protein-DNA complex. The characterization of the pattern of evolution in known binding sites will likely contribute to the

  6. Whole-genome and multisector exome sequencing of primary and post-treatment glioblastoma reveals patterns of tumor evolution.

    PubMed

    Kim, Hoon; Zheng, Siyuan; Amini, Seyed S; Virk, Selene M; Mikkelsen, Tom; Brat, Daniel J; Grimsby, Jonna; Sougnez, Carrie; Muller, Florian; Hu, Jian; Sloan, Andrew E; Cohen, Mark L; Van Meir, Erwin G; Scarpace, Lisa; Laird, Peter W; Weinstein, John N; Lander, Eric S; Gabriel, Stacey; Getz, Gad; Meyerson, Matthew; Chin, Lynda; Barnholtz-Sloan, Jill S; Verhaak, Roel G W

    2015-03-01

    Glioblastoma (GBM) is a prototypical heterogeneous brain tumor refractory to conventional therapy. A small residual population of cells escapes surgery and chemoradiation, resulting in a typically fatal tumor recurrence ∼ 7 mo after diagnosis. Understanding the molecular architecture of this residual population is critical for the development of successful therapies. We used whole-genome sequencing and whole-exome sequencing of multiple sectors from primary and paired recurrent GBM tumors to reconstruct the genomic profile of residual, therapy resistant tumor initiating cells. We found that genetic alteration of the p53 pathway is a primary molecular event predictive of a high number of subclonal mutations in glioblastoma. The genomic road leading to recurrence is highly idiosyncratic but can be broadly classified into linear recurrences that share extensive genetic similarity with the primary tumor and can be directly traced to one of its specific sectors, and divergent recurrences that share few genetic alterations with the primary tumor and originate from cells that branched off early during tumorigenesis. Our study provides mechanistic insights into how genetic alterations in primary tumors impact the ensuing evolution of tumor cells and the emergence of subclonal heterogeneity. © 2015 Kim et al.; Published by Cold Spring Harbor Laboratory Press.

  7. Temporal evolution of a seismic sequence induced by a gas injection in the Eastern coast of Spain.

    PubMed

    Ruiz-Barajas, S; Sharma, N; Convertito, V; Zollo, A; Benito, B

    2017-06-06

    Induced seismicity associated with energy production is becoming an increasingly important issue worldwide for the hazard it poses to the exposed population and structures. We analyze one of the rare cases of induced seismicity associated with the underwater gas storage operations observed in the Castor platform, located in the Valencia gulf, east Spain, near a complex and important geological structure. In September 2013, some gas injection operations started at Castor, producing a series of seismic events around the reservoir area. The larger magnitude events (up to 4.2) took place some days after the end of the injection, with EMS intensities in coastal towns up to degree III. In this work, the seismic sequence is analyzed with the aim of detecting changes in statistical parameters describing the earthquake occurrence before and after the injection and identifying possible proxies to be used for monitoring the sequence evolution. Moreover, we explore the potential predictability of these statistical parameters which can be used to control the field operations in injection/storage fluid reservoirs. We firstly perform a retrospective approach and next a perspective analysis. We use different techniques for estimating the value of the expected maximum magnitude that can occur due to antropogenic activities in Castor.

  8. Co-evolution of electric and telecommunications networks

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rivkin, S.R.

    1998-05-01

    There are potentially significant societal benefits in co-evolution between electricity and telecommunications in the areas of common infrastructure, accelerated deployment of distributed energy, tighter integration of information flow for energy management and distribution, and improved customer care. With due regard for natural processes that are more potent than any regulation and more real than any ideology, the gains from co-evolution would far outweigh the attenuated and speculative savings from restructuring of electricity that is too simplistic.

  9. Next-generation sequencing based genotyping, cytometry and phenotyping for understanding diversity and evolution of Guinea yams.

    PubMed

    Girma, Gezahegn; Hyma, Katie E; Asiedu, Robert; Mitchell, Sharon E; Gedil, Melaku; Spillane, Charles

    2014-08-01

    Genotyping by sequencing (GBS) is used to understand the origin and domestication of guinea yams, including the contribution of wild relatives and polyploidy events to the cultivated guinea yams. Patterns of genetic diversity within and between two cultivated guinea yams (Dioscorea rotundata and D. cayenensis) and five wild relatives (D. praehensilis, D. mangenotiana, D. abyssinica, D. togoensis and D. burkilliana) were investigated using next-generation sequencing (genotyping by sequencing, GBS). Additionally, the two cultivated species were assessed for intra-specific morphological and ploidy variation. In guinea yams, ploidy level is correlated with species identity. Using flow cytometry a single ploidy level was inferred across D. cayenensis (3x, N = 21), D. praehensilis (2x, N = 7), and D. mangenotiana (3x, N = 5) accessions, whereas both diploid and triploid (or aneuploid) accessions were present in D. rotundata (N = 11 and N = 32, respectively). Multi-dimensional scaling and maximum parsimony analyses of 2,215 SNPs revealed that wild guinea yam populations form discrete genetic groupings according to species. D. togoensis and D. burkilliana were most distant from the two cultivated yam species, whereas D. abyssinica, D. mangenotiana, and D. praehensilis were closest to cultivated yams. In contrast, cultivated species were genetically less clearly defined at the intra-specific level. While D. cayenensis formed a single genetic group, D. rotundata comprised three separate groups consisting of; (1) a set of diploid individuals genetically similar to D. praehensilis, (2) a set of diploid individuals genetically similar to D. cayenensis, and (3) a set of triploid individuals. The current study demonstrates the utility of GBS for assessing yam genomic diversity. Combined with morphological and biological data, GBS provides a powerful tool for testing hypotheses regarding the evolution, domestication and breeding of guinea yams.

  10. A high density physical map of chromosome 1BL supports evolutionary studies, map-based cloning and sequencing in wheat

    PubMed Central

    2013-01-01

    Background As for other major crops, achieving a complete wheat genome sequence is essential for the application of genomics to breeding new and improved varieties. To overcome the complexities of the large, highly repetitive and hexaploid wheat genome, the International Wheat Genome Sequencing Consortium established a chromosome-based strategy that was validated by the construction of the physical map of chromosome 3B. Here, we present improved strategies for the construction of highly integrated and ordered wheat physical maps, using chromosome 1BL as a template, and illustrate their potential for evolutionary studies and map-based cloning. Results Using a combination of novel high throughput marker assays and an assembly program, we developed a high quality physical map representing 93% of wheat chromosome 1BL, anchored and ordered with 5,489 markers including 1,161 genes. Analysis of the gene space organization and evolution revealed that gene distribution and conservation along the chromosome results from the superimposition of the ancestral grass and recent wheat evolutionary patterns, leading to a peak of synteny in the central part of the chromosome arm and an increased density of non-collinear genes towards the telomere. With a density of about 11 markers per Mb, the 1BL physical map provides 916 markers, including 193 genes, for fine mapping the 40 QTLs mapped on this chromosome. Conclusions Here, we demonstrate that high marker density physical maps can be developed in complex genomes such as wheat to accelerate map-based cloning, gain new insights into genome evolution, and provide a foundation for reference sequencing. PMID:23800011

  11. Investigation of the protein osteocalcin of Camelops hesternus: Sequence, structure and phylogenetic implications

    NASA Astrophysics Data System (ADS)

    Humpula, James F.; Ostrom, Peggy H.; Gandhi, Hasand; Strahler, John R.; Walker, Angela K.; Stafford, Thomas W.; Smith, James J.; Voorhies, Michael R.; George Corner, R.; Andrews, Phillip C.

    2007-12-01

    Ancient DNA sequences offer an extraordinary opportunity to unravel the evolutionary history of ancient organisms. Protein sequences offer another reservoir of genetic information that has recently become tractable through the application of mass spectrometric techniques. The extent to which ancient protein sequences resolve phylogenetic relationships, however, has not been explored. We determined the osteocalcin amino acid sequence from the bone of an extinct Camelid (21 ka, Camelops hesternus) excavated from Isleta Cave, New Mexico and three bones of extant camelids: bactrian camel ( Camelus bactrianus); dromedary camel ( Camelus dromedarius) and guanaco ( Llama guanacoe) for a diagenetic and phylogenetic assessment. There was no difference in sequence among the four taxa. Structural attributes observed in both modern and ancient osteocalcin include a post-translation modification, Hyp 9, deamidation of Gln 35 and Gln 39, and oxidation of Met 36. Carbamylation of the N-terminus in ancient osteocalcin may result in blockage and explain previous difficulties in sequencing ancient proteins via Edman degradation. A phylogenetic analysis using osteocalcin sequences of 25 vertebrate taxa was conducted to explore osteocalcin protein evolution and the utility of osteocalcin sequences for delineating phylogenetic relationships. The maximum likelihood tree closely reflected generally recognized taxonomic relationships. For example, maximum likelihood analysis recovered rodents, birds and, within hominins, the Homo-Pan-Gorilla trichotomy. Within Artiodactyla, character state analysis showed that a substitution of Pro 4 for His 4 defines the Capra-Ovis clade within Artiodactyla. Homoplasy in our analysis indicated that osteocalcin evolution is not a perfect indicator of species evolution. Limited sequence availability prevented assigning functional significance to sequence changes. Our preliminary analysis of osteocalcin evolution represents an initial step towards a

  12. Guidelines for investigating causality of sequence variants in human disease

    PubMed Central

    MacArthur, D. G.; Manolio, T. A.; Dimmock, D. P.; Rehm, H. L.; Shendure, J.; Abecasis, G. R.; Adams, D. R.; Altman, R. B.; Antonarakis, S. E.; Ashley, E. A.; Barrett, J. C.; Biesecker, L. G.; Conrad, D. F.; Cooper, G. M.; Cox, N. J.; Daly, M. J.; Gerstein, M. B.; Goldstein, D. B.; Hirschhorn, J. N.; Leal, S. M.; Pennacchio, L. A.; Stamatoyannopoulos, J. A.; Sunyaev, S. R.; Valle, D.; Voight, B. F.; Winckler, W.; Gunter, C.

    2014-01-01

    The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. PMID:24759409

  13. Guidelines for investigating causality of sequence variants in human disease.

    PubMed

    MacArthur, D G; Manolio, T A; Dimmock, D P; Rehm, H L; Shendure, J; Abecasis, G R; Adams, D R; Altman, R B; Antonarakis, S E; Ashley, E A; Barrett, J C; Biesecker, L G; Conrad, D F; Cooper, G M; Cox, N J; Daly, M J; Gerstein, M B; Goldstein, D B; Hirschhorn, J N; Leal, S M; Pennacchio, L A; Stamatoyannopoulos, J A; Sunyaev, S R; Valle, D; Voight, B F; Winckler, W; Gunter, C

    2014-04-24

    The discovery of rare genetic variants is accelerating, and clear guidelines for distinguishing disease-causing sequence variants from the many potentially functional variants present in any human genome are urgently needed. Without rigorous standards we risk an acceleration of false-positive reports of causality, which would impede the translation of genomic research findings into the clinical diagnostic setting and hinder biological understanding of disease. Here we discuss the key challenges of assessing sequence variants in human disease, integrating both gene-level and variant-level support for causality. We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development.

  14. Direct and accelerated parameter mapping using the unscented Kalman filter.

    PubMed

    Zhao, Li; Feng, Xue; Meyer, Craig H

    2016-05-01

    To accelerate parameter mapping using a new paradigm that combines image reconstruction and model regression as a parameter state-tracking problem. In T2 mapping, the T2 map is first encoded in parameter space by multi-TE measurements and then encoded by Fourier transformation with readout/phase encoding gradients. Using a state transition function and a measurement function, the unscented Kalman filter can describe T2 mapping as a dynamic system and directly estimate the T2 map from the k-space data. The proposed method was validated with a numerical brain phantom and volunteer experiments with a multiple-contrast spin echo sequence. Its performance was compared with a conjugate-gradient nonlinear inversion method at undersampling factors of 2 to 8. An accelerated pulse sequence was developed based on this method to achieve prospective undersampling. Compared with the nonlinear inversion reconstruction, the proposed method had higher precision, improved structural similarity and reduced normalized root mean squared error, with acceleration factors up to 8 in numerical phantom and volunteer studies. This work describes a new perspective on parameter mapping by state tracking. The unscented Kalman filter provides a highly accelerated and efficient paradigm for T2 mapping. © 2015 Wiley Periodicals, Inc.

  15. Accurate modeling of the hose instability in plasma wakefield accelerators

    DOE PAGES

    Mehrling, T. J.; Benedetti, C.; Schroeder, C. B.; ...

    2018-05-20

    Hosing is a major challenge for the applicability of plasma wakefield accelerators and its modeling is therefore of fundamental importance to facilitate future stable and compact plasma-based particle accelerators. In this contribution, we present a new model for the evolution of the plasma centroid, which enables the accurate investigation of the hose instability in the nonlinear blowout regime. Lastly, it paves the road for more precise and comprehensive studies of hosing, e.g., with drive and witness beams, which were not possible with previous models.

  16. Accurate modeling of the hose instability in plasma wakefield accelerators

    NASA Astrophysics Data System (ADS)

    Mehrling, T. J.; Benedetti, C.; Schroeder, C. B.; Martinez de la Ossa, A.; Osterhoff, J.; Esarey, E.; Leemans, W. P.

    2018-05-01

    Hosing is a major challenge for the applicability of plasma wakefield accelerators and its modeling is therefore of fundamental importance to facilitate future stable and compact plasma-based particle accelerators. In this contribution, we present a new model for the evolution of the plasma centroid, which enables the accurate investigation of the hose instability in the nonlinear blowout regime. It paves the road for more precise and comprehensive studies of hosing, e.g., with drive and witness beams, which were not possible with previous models.

  17. Accurate modeling of the hose instability in plasma wakefield accelerators

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mehrling, T. J.; Benedetti, C.; Schroeder, C. B.

    Hosing is a major challenge for the applicability of plasma wakefield accelerators and its modeling is therefore of fundamental importance to facilitate future stable and compact plasma-based particle accelerators. In this contribution, we present a new model for the evolution of the plasma centroid, which enables the accurate investigation of the hose instability in the nonlinear blowout regime. Lastly, it paves the road for more precise and comprehensive studies of hosing, e.g., with drive and witness beams, which were not possible with previous models.

  18. Understanding the evolution and spread of chikungunya virus in the Americas using complete genome sequences.

    PubMed

    Sahadeo, N S D; Allicock, O M; De Salazar, P M; Auguste, A J; Widen, S; Olowokure, B; Gutierrez, C; Valadere, A M; Polson-Edwards, K; Weaver, S C; Carrington, C V F

    2017-01-01

    Local transmission of chikungunya virus (CHIKV) was first detected in the Americas in December 2013, after which it spread rapidly throughout the Caribbean islands and American mainland, causing a major chikungunya fever epidemic. Previous phylogenetic analysis of CHIKV from a limited number of countries in the Americas suggests that an Asian genotype strain was responsible, except in Brazil where both Asian and East/Central/South African (ECSA) lineage strains were detected. In this study, we sequenced thirty-three complete CHIKV genomes from viruses isolated in 2014 from fourteen Caribbean islands, the Bahamas and two mainland countries in the Americas. Phylogenetic analyses confirmed that they all belonged to the Asian genotype and clustered together with other Caribbean and mainland sequences isolated during the American outbreak, forming an 'Asian/American' lineage defined by two amino acid substitutions, E2 V368A and 6K L20M, and divided into two well-supported clades. This lineage is estimated to be evolving at a mean rate of 5 × 10 -4 substitutions per site per year (95% higher probability density, 2.9-7.9 × 10 -4 ) and to have arisen from an ancestor introduced to the Caribbean (most likely from Oceania) in about March 2013, 9 months prior to the first report of CHIKV in the Americas. Estimation of evolutionary rates for individual gene regions and selection analyses indicate that (in contrast to the Indian Ocean Lineage that emerged from the ECSA genotype followed by adaptive evolution and with a significantly higher substitution rate) the evolutionary dynamics of the Asian/American lineage are very similar to the rest of the Asian genotype and natural selection does not appear to have played a major role in its emergence. However, several codon sites with evidence of positive selection were identified within the non-structural regions of Asian genotype sequences outside of the Asian/American lineage.

  19. Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120.

    PubMed

    deCamp, Allan C; Rolland, Morgane; Edlefsen, Paul T; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A; Fiore-Gartland, Andrew J; Juraska, Michal; Carpp, Lindsay N; Karuna, Shelly T; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z; Gottardo, Raphael; Koup, Richard A; Bailer, Robert; Mascola, John R; Graham, Barney S; Roederer, Mario; O'Connell, Robert J; Michael, Nelson L; Robb, Merlin L; Adams, Elizabeth; D'Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E; Frahm, Nicole; Tomaras, Georgia D; McElrath, M Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E; Hammer, Scott M; Kim, Jerome H; Mullins, James I; Gilbert, Peter B

    2017-01-01

    Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector.

  20. Sieve analysis of breakthrough HIV-1 sequences in HVTN 505 identifies vaccine pressure targeting the CD4 binding site of Env-gp120

    PubMed Central

    Edlefsen, Paul T.; Sanders-Buell, Eric; Hall, Breana; Magaret, Craig A.; Fiore-Gartland, Andrew J.; Juraska, Michal; Carpp, Lindsay N.; Karuna, Shelly T.; Bose, Meera; LePore, Steven; Miller, Shana; O'Sullivan, Annemarie; Poltavee, Kultida; Bai, Hongjun; Dommaraju, Kalpana; Zhao, Hong; Wong, Kim; Chen, Lennie; Ahmed, Hasan; Goodman, Derrick; Tay, Matthew Z.; Gottardo, Raphael; Koup, Richard A.; Bailer, Robert; Mascola, John R.; Graham, Barney S.; Roederer, Mario; O’Connell, Robert J.; Michael, Nelson L.; Robb, Merlin L.; Adams, Elizabeth; D’Souza, Patricia; Kublin, James; Corey, Lawrence; Geraghty, Daniel E.; Frahm, Nicole; Tomaras, Georgia D.; McElrath, M. Juliana; Frenkel, Lisa; Styrchak, Sheila; Tovanabutra, Sodsai; Sobieszczyk, Magdalena E.; Hammer, Scott M.; Kim, Jerome H.; Mullins, James I.; Gilbert, Peter B.

    2017-01-01

    Although the HVTN 505 DNA/recombinant adenovirus type 5 vector HIV-1 vaccine trial showed no overall efficacy, analysis of breakthrough HIV-1 sequences in participants can help determine whether vaccine-induced immune responses impacted viruses that caused infection. We analyzed 480 HIV-1 genomes sampled from 27 vaccine and 20 placebo recipients and found that intra-host HIV-1 diversity was significantly lower in vaccine recipients (P ≤ 0.04, Q-values ≤ 0.09) in Gag, Pol, Vif and envelope glycoprotein gp120 (Env-gp120). Furthermore, Env-gp120 sequences from vaccine recipients were significantly more distant from the subtype B vaccine insert than sequences from placebo recipients (P = 0.01, Q-value = 0.12). These vaccine effects were associated with signatures mapping to CD4 binding site and CD4-induced monoclonal antibody footprints. These results suggest either (i) no vaccine efficacy to block acquisition of any viral genotype but vaccine-accelerated Env evolution post-acquisition; or (ii) vaccine efficacy against HIV-1s with Env sequences closest to the vaccine insert combined with increased acquisition due to other factors, potentially including the vaccine vector. PMID:29149197

  1. The evolution of massive stars and their spectra. I. A non-rotating 60 M⊙ star from the zero-age main sequence to the pre-supernova stage

    NASA Astrophysics Data System (ADS)

    Groh, Jose H.; Meynet, Georges; Ekström, Sylvia; Georgy, Cyril

    2014-04-01

    For the first time, the interior and spectroscopic evolution of a massive star is analyzed from the zero-age main sequence (ZAMS) to the pre-supernova (SN) stage. For this purpose, we combined stellar evolution models using the Geneva code and stellar atmospheric/wind models using CMFGEN. With our approach, we were able to produce observables, such as a synthetic high-resolution spectrum and photometry, thereby aiding the comparison between evolution models and observed data. Here we analyze the evolution of a non-rotating 60 M⊙ star and its spectrum throughout its lifetime. Interestingly, the star has a supergiant appearance (luminosity class I) even at the ZAMS. We find the following evolutionary sequence of spectral types: O3 I (at the ZAMS), O4 I (middle of the H-core burning phase), B supergiant (BSG), B hypergiant (BHG), hot luminous blue variable (LBV; end of H-core burning), cool LBV (H-shell burning through the beginning of the He-core burning phase), rapid evolution through late WN and early WN, early WC (middle of He-core burning), and WO (end of He-core burning until core collapse). We find the following spectroscopic phase lifetimes: 3.22 × 106 yr for the O-type, 0.34 × 105 yr (BSG), 0.79 × 105 yr (BHG), 2.35 × 105 yr (LBV), 1.05 × 105 yr (WN), 2.57 × 105 yr (WC), and 3.80 × 104 yr (WO). Compared to previous studies, we find a much longer (shorter) duration for the early WN (late WN) phase, as well as a long-lived LBV phase. We show that LBVs arise naturally in single-star evolution models at the end of the MS when the mass-loss rate increases as a consequence of crossing the bistability limit. We discuss the evolution of the spectra, magnitudes, colors, and ionizing flux across the star's lifetime, and the way they are related to the evolution of the interior. We find that the absolute magnitude of the star typically changes by ~6 mag in optical filters across the evolution, with the star becoming significantly fainter in optical filters at

  2. The evolution processes of DNA sequences, languages and carols

    NASA Astrophysics Data System (ADS)

    Hauck, Jürgen; Henkel, Dorothea; Mika, Klaus

    2001-04-01

    The sequences of bases A, T, C and G of about 100 enolase, secA and cytochrome DNA were analyzed for attractive or repulsive interactions by the numbers T 1,T 2,T 3; r of nearest, next-nearest and third neighbor bases of the same kind and the concentration r=other bases/analyzed base. The area of possible T1, T2 values is limited by the linear borders T 2=2T 1-2, T 2=0 or T1=0 for clustering, attractive or repulsive interactions and the border T2=-2 T1+2(2- r) for a variation from repulsive to attractive interactions at r⩽2. Clustering is preferred by most bases in sequences of enolases and secA’ s. Major deviations with repulsive interactions of some bases are observed for archaea bacteria in secA and for highly developed animals and the human species in enolase sequences. The borders of the structure map for enthalpy stabilized structures with maximum interactions are approached in few cases. Most letters of the natural languages and some music notes are at the borders of the structure map.

  3. Insights into the evolution of Darwin’s finches from comparative analysis of the Geospiza magnirostris genome sequence

    PubMed Central

    2013-01-01

    Background A classical example of repeated speciation coupled with ecological diversification is the evolution of 14 closely related species of Darwin’s (Galápagos) finches (Thraupidae, Passeriformes). Their adaptive radiation in the Galápagos archipelago took place in the last 2–3 million years and some of the molecular mechanisms that led to their diversification are now being elucidated. Here we report evolutionary analyses of genome of the large ground finch, Geospiza magnirostris. Results 13,291 protein-coding genes were predicted from a 991.0 Mb G. magnirostris genome assembly. We then defined gene orthology relationships and constructed whole genome alignments between the G. magnirostris and other vertebrate genomes. We estimate that 15% of genomic sequence is functionally constrained between G. magnirostris and zebra finch. Genic evolutionary rate comparisons indicate that similar selective pressures acted along the G. magnirostris and zebra finch lineages suggesting that historical effective population size values have been similar in both lineages. 21 otherwise highly conserved genes were identified that each show evidence for positive selection on amino acid changes in the Darwin's finch lineage. Two of these genes (Igf2r and Pou1f1) have been implicated in beak morphology changes in Darwin’s finches. Five of 47 genes showing evidence of positive selection in early passerine evolution have cilia related functions, and may be examples of adaptively evolving reproductive proteins. Conclusions These results provide insights into past evolutionary processes that have shaped G. magnirostris genes and its genome, and provide the necessary foundation upon which to build population genomics resources that will shed light on more contemporaneous adaptive and non-adaptive processes that have contributed to the evolution of the Darwin’s finches. PMID:23402223

  4. Evolution and advection of solar mesogranulation

    NASA Technical Reports Server (NTRS)

    Muller, Richard; Auffret, Herve; Roudier, Thierry; Vigneau, Jean; Simon, George W.; Frank, Zoe; Shine, Richard A.; Title, Alan M.

    1992-01-01

    A three-hour sequence of observations at the Pic du Midi observatory has been obtained which shows the evolution of solar mesogranules from appearance to disappearance with unprecedented clarity. It is seen that the supergranules, which are known to advect the granules with their convective motion, also advect the mesogranules to their boundaries. This process controls the evolution and disappearance of mesogranules.

  5. Improvisation in evolution of genes and genomes: whose structure is it anyway?

    PubMed

    Shakhnovich, Boris E; Shakhnovich, Eugene I

    2008-06-01

    Significant progress has been made in recent years in a variety of seemingly unrelated fields such as sequencing, protein structure prediction, and high-throughput transcriptomics and metabolomics. At the same time, new microscopic models have been developed that made it possible to analyze the evolution of genes and genomes from first principles. The results from these efforts enable, for the first time, a comprehensive insight into the evolution of complex systems and organisms on all scales--from sequences to organisms and populations. Every newly sequenced genome uncovers new genes, families, and folds. Where do these new genes come from? How do gene duplication and subsequent divergence of sequence and structure affect the fitness of the organism? What role does regulation play in the evolution of proteins and folds? Emerging synergism between data and modeling provides first robust answers to these questions.

  6. The acceleration of charged particles in interplanetary shock waves

    NASA Technical Reports Server (NTRS)

    Pesses, M. E.; Decker, R. B.; Armstrong, T. P.

    1982-01-01

    Consideration of the theoretical and observational literature on energetic ion acceleration in interplanetary shock waves is the basis for the present discussion of the shock acceleration of the solar wind plasma and particle transport effects. It is suggested that ISEE data be used to construct data sets for shock events that extend continuously from solar wind to galactic cosmic ray energies, including data for electrons, protons, alphas and ions with Z values greater than 2.0, and that the temporal and spatial evolution of two- and three-dimensional particle distribution functions be studied by means of two or more spacecraft.

  7. Interspecific Plastome Recombination Reflects Ancient Reticulate Evolution in Picea (Pinaceae).

    PubMed

    Sullivan, Alexis R; Schiffthaler, Bastian; Thompson, Stacey Lee; Street, Nathaniel R; Wang, Xiao-Ru

    2017-07-01

    Plastid sequences are a cornerstone in plant systematic studies and key aspects of their evolution, such as uniparental inheritance and absent recombination, are often treated as axioms. While exceptions to these assumptions can profoundly influence evolutionary inference, detecting them can require extensive sampling, abundant sequence data, and detailed testing. Using advancements in high-throughput sequencing, we analyzed the whole plastomes of 65 accessions of Picea, a genus of ∼35 coniferous forest tree species, to test for deviations from canonical plastome evolution. Using complementary hypothesis and data-driven tests, we found evidence for chimeric plastomes generated by interspecific hybridization and recombination in the clade comprising Norway spruce (P. abies) and 10 other species. Support for interspecific recombination remained after controlling for sequence saturation, positive selection, and potential alignment artifacts. These results reconcile previous conflicting plastid-based phylogenies and strengthen the mounting evidence of reticulate evolution in Picea. Given the relatively high frequency of hybridization and biparental plastid inheritance in plants, we suggest interspecific plastome recombination may be more widespread than currently appreciated and could underlie reported cases of discordant plastid phylogenies. © The Author 2017. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution.

  8. Relaxed evolution in the tyrosine aminotransferase gene tat in old world fruit bats (Chiroptera: Pteropodidae).

    PubMed

    Shen, Bin; Fang, Tao; Yang, Tianxiao; Jones, Gareth; Irwin, David M; Zhang, Shuyi

    2014-01-01

    Frugivorous and nectarivorous bats fuel their metabolism mostly by using carbohydrates and allocate the restricted amounts of ingested proteins mainly for anabolic protein syntheses rather than for catabolic energy production. Thus, it is possible that genes involved in protein (amino acid) catabolism may have undergone relaxed evolution in these fruit- and nectar-eating bats. The tyrosine aminotransferase (TAT, encoded by the Tat gene) is the rate-limiting enzyme in the tyrosine catabolic pathway. To test whether the Tat gene has undergone relaxed evolution in the fruit- and nectar-eating bats, we obtained the Tat coding region from 20 bat species including four Old World fruit bats (Pteropodidae) and two New World fruit bats (Phyllostomidae). Phylogenetic reconstructions revealed a gene tree in which all echolocating bats (including the New World fruit bats) formed a monophyletic group. The phylogenetic conflict appears to stem from accelerated TAT protein sequence evolution in the Old World fruit bats. Our molecular evolutionary analyses confirmed a change in the selection pressure acting on Tat, which was likely caused by a relaxation of the evolutionary constraints on the Tat gene in the Old World fruit bats. Hepatic TAT activity assays showed that TAT activities in species of the Old World fruit bats are significantly lower than those of insectivorous bats and omnivorous mice, which was not caused by a change in TAT protein levels in the liver. Our study provides unambiguous evidence that the Tat gene has undergone relaxed evolution in the Old World fruit bats in response to changes in their metabolism due to the evolution of their special diet.

  9. Estuarine wetland evolution including sea-level rise and infrastructure effects.

    NASA Astrophysics Data System (ADS)

    Rodriguez, Jose Fernando; Trivisonno, Franco; Rojas, Steven Sandi; Riccardi, Gerardo; Stenta, Hernan; Saco, Patricia Mabel

    2015-04-01

    Estuarine wetlands are an extremely valuable resource in terms of biotic diversity, flood attenuation, storm surge protection, groundwater recharge, filtering of surface flows and carbon sequestration. On a large scale the survival of these systems depends on the slope of the land and a balance between the rates of accretion and sea-level rise, but local man-made flow disturbances can have comparable effects. Climate change predictions for most of Australia include an accelerated sea level rise, which may challenge the survival of estuarine wetlands. Furthermore, coastal infrastructure poses an additional constraint on the adaptive capacity of these ecosystems. Numerical models are increasingly being used to assess wetland dynamics and to help manage some of these situations. We present results of a wetland evolution model that is based on computed values of hydroperiod and tidal range that drive vegetation preference. Our first application simulates the long term evolution of an Australian wetland heavily constricted by infrastructure that is undergoing the effects of predicted accelerated sea level rise. The wetland presents a vegetation zonation sequence mudflats - mangrove - saltmarsh from the seaward margin and up the topographic gradient but is also affected by compartmentalization due to internal road embankments and culverts that effectively attenuates tidal input to the upstream compartments. For this reason, the evolution model includes a 2D hydrodynamic module which is able to handle man-made flow controls and spatially varying roughness. It continually simulates tidal inputs into the wetland and computes annual values of hydroperiod and tidal range to update vegetation distribution based on preference to hydrodynamic conditions of the different vegetation types. It also computes soil accretion rates and updates roughness coefficient values according to evolving vegetation types. In order to explore in more detail the magnitude of flow attenuation due to

  10. Energy Level Engineering of MoS2 by Transition-Metal Doping for Accelerating Hydrogen Evolution Reaction.

    PubMed

    Shi, Yi; Zhou, Yue; Yang, Dong-Rui; Xu, Wei-Xuan; Wang, Chen; Wang, Feng-Bin; Xu, Jing-Juan; Xia, Xing-Hua; Chen, Hong-Yuan

    2017-11-01

    Water-splitting devices for hydrogen generation through electrolysis (hydrogen evolution reaction, HER) hold great promise for clean energy. However, their practical application relies on the development of inexpensive and efficient catalysts to replace precious platinum catalysts. We previously reported that HER can be largely enhanced through finely tuning the energy level of molybdenum sulfide (MoS 2 ) by hot electron injection from plasmonic gold nanoparticles. Under this inspiration, herein, we propose a strategy to improve the HER performance of MoS 2 by engineering its energy level via direct transition-metal doping. We find that zinc-doped MoS 2 (Zn-MoS 2 ) exhibits superior electrochemical activity toward HER as evidenced by the positively shifted onset potential to -0.13 V vs RHE. A turnover of 15.44 s -1 at 300 mV overpotential is achieved, which by far exceeds the activity of MoS 2 catalysts reported. The large enhancement can be attributed to the synergistic effect of electronic effect (energy level matching) and morphological effect (rich active sites) via thermodynamic and kinetic acceleration, respectively. This design opens up further opportunities for improving electrocatalysts by incorporating promoters, which broadens the understanding toward the optimization of electrocatalytic activity of these unique materials.

  11. Biophysics of protein evolution and evolutionary protein biophysics

    PubMed Central

    Sikosek, Tobias; Chan, Hue Sun

    2014-01-01

    The study of molecular evolution at the level of protein-coding genes often entails comparing large datasets of sequences to infer their evolutionary relationships. Despite the importance of a protein's structure and conformational dynamics to its function and thus its fitness, common phylogenetic methods embody minimal biophysical knowledge of proteins. To underscore the biophysical constraints on natural selection, we survey effects of protein mutations, highlighting the physical basis for marginal stability of natural globular proteins and how requirement for kinetic stability and avoidance of misfolding and misinteractions might have affected protein evolution. The biophysical underpinnings of these effects have been addressed by models with an explicit coarse-grained spatial representation of the polypeptide chain. Sequence–structure mappings based on such models are powerful conceptual tools that rationalize mutational robustness, evolvability, epistasis, promiscuous function performed by ‘hidden’ conformational states, resolution of adaptive conflicts and conformational switches in the evolution from one protein fold to another. Recently, protein biophysics has been applied to derive more accurate evolutionary accounts of sequence data. Methods have also been developed to exploit sequence-based evolutionary information to predict biophysical behaviours of proteins. The success of these approaches demonstrates a deep synergy between the fields of protein biophysics and protein evolution. PMID:25165599

  12. Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality.

    PubMed

    Wei, Chaoling; Yang, Hua; Wang, Songbo; Zhao, Jian; Liu, Chun; Gao, Liping; Xia, Enhua; Lu, Ying; Tai, Yuling; She, Guangbiao; Sun, Jun; Cao, Haisheng; Tong, Wei; Gao, Qiang; Li, Yeyun; Deng, Weiwei; Jiang, Xiaolan; Wang, Wenzhao; Chen, Qi; Zhang, Shihua; Li, Haijing; Wu, Junlan; Wang, Ping; Li, Penghui; Shi, Chengying; Zheng, Fengya; Jian, Jianbo; Huang, Bei; Shan, Dai; Shi, Mingming; Fang, Congbing; Yue, Yi; Li, Fangdong; Li, Daxiang; Wei, Shu; Han, Bin; Jiang, Changjun; Yin, Ye; Xia, Tao; Zhang, Zhengzhu; Bennetzen, Jeffrey L; Zhao, Shancen; Wan, Xiaochun

    2018-05-01

    Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to ∼0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred ∼30 to 40 and ∼90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties. Copyright © 2018 the Author(s). Published by PNAS.

  13. Clinical Sequencing Exploratory Research Consortium: Accelerating Evidence-Based Practice of Genomic Medicine.

    PubMed

    Green, Robert C; Goddard, Katrina A B; Jarvik, Gail P; Amendola, Laura M; Appelbaum, Paul S; Berg, Jonathan S; Bernhardt, Barbara A; Biesecker, Leslie G; Biswas, Sawona; Blout, Carrie L; Bowling, Kevin M; Brothers, Kyle B; Burke, Wylie; Caga-Anan, Charlisse F; Chinnaiyan, Arul M; Chung, Wendy K; Clayton, Ellen W; Cooper, Gregory M; East, Kelly; Evans, James P; Fullerton, Stephanie M; Garraway, Levi A; Garrett, Jeremy R; Gray, Stacy W; Henderson, Gail E; Hindorff, Lucia A; Holm, Ingrid A; Lewis, Michelle Huckaby; Hutter, Carolyn M; Janne, Pasi A; Joffe, Steven; Kaufman, David; Knoppers, Bartha M; Koenig, Barbara A; Krantz, Ian D; Manolio, Teri A; McCullough, Laurence; McEwen, Jean; McGuire, Amy; Muzny, Donna; Myers, Richard M; Nickerson, Deborah A; Ou, Jeffrey; Parsons, Donald W; Petersen, Gloria M; Plon, Sharon E; Rehm, Heidi L; Roberts, J Scott; Robinson, Dan; Salama, Joseph S; Scollon, Sarah; Sharp, Richard R; Shirts, Brian; Spinner, Nancy B; Tabor, Holly K; Tarczy-Hornoch, Peter; Veenstra, David L; Wagle, Nikhil; Weck, Karen; Wilfond, Benjamin S; Wilhelmsen, Kirk; Wolf, Susan M; Wynn, Julia; Yu, Joon-Ho

    2016-06-02

    Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine. Copyright © 2016 American Society of Human Genetics. All rights reserved.

  14. Protein 3D Structure Computed from Evolutionary Sequence Variation

    PubMed Central

    Sheridan, Robert; Hopf, Thomas A.; Pagnani, Andrea; Zecchina, Riccardo; Sander, Chris

    2011-01-01

    The evolutionary trajectory of a protein through sequence space is constrained by its function. Collections of sequence homologs record the outcomes of millions of evolutionary experiments in which the protein evolves according to these constraints. Deciphering the evolutionary record held in these sequences and exploiting it for predictive and engineering purposes presents a formidable challenge. The potential benefit of solving this challenge is amplified by the advent of inexpensive high-throughput genomic sequencing. In this paper we ask whether we can infer evolutionary constraints from a set of sequence homologs of a protein. The challenge is to distinguish true co-evolution couplings from the noisy set of observed correlations. We address this challenge using a maximum entropy model of the protein sequence, constrained by the statistics of the multiple sequence alignment, to infer residue pair couplings. Surprisingly, we find that the strength of these inferred couplings is an excellent predictor of residue-residue proximity in folded structures. Indeed, the top-scoring residue couplings are sufficiently accurate and well-distributed to define the 3D protein fold with remarkable accuracy. We quantify this observation by computing, from sequence alone, all-atom 3D structures of fifteen test proteins from different fold classes, ranging in size from 50 to 260 residues., including a G-protein coupled receptor. These blinded inferences are de novo, i.e., they do not use homology modeling or sequence-similar fragments from known structures. The co-evolution signals provide sufficient information to determine accurate 3D protein structure to 2.7–4.8 Å Cα-RMSD error relative to the observed structure, over at least two-thirds of the protein (method called EVfold, details at http://EVfold.org). This discovery provides insight into essential interactions constraining protein evolution and will facilitate a comprehensive survey of the universe of protein

  15. Dynamic evolution at pericentromeres.

    PubMed

    Hall, Anne E; Kettler, Gregory C; Preuss, Daphne

    2006-03-01

    Pericentromeres are exceptional genomic regions: in animals they contain extensive segmental duplications implicated in gene creation, and in plants they sustain rearrangements and insertions uncommon in euchromatin. To examine the mechanisms and patterns of plant pericentromere evolution, we compared pericentromere sequence from four Brassicaceae species separated by <15 million years (Myr). This flowering plant family is ideal for studying relationships between genome reorganization and pericentromere evolution-its members have undergone recent polyploidization and hybridization, with close relatives changing in genome size and chromosome number. Through sequence and hybridization analyses, we examined regions from Arabidopsis arenosa, Capsella rubella, and Olimarabidopsis pumila that are homologous to Arabidopsis thaliana pericentromeres (peri-CENs) III and V, and used FISH to demonstrate they have been maintained near centromere satellite arrays in each species. Sequence analysis revealed a set of highly conserved genes, yet we discovered substantial differences in intergenic length and species-specific changes in sequence content and gene density. We discovered that A. thaliana has undergone recent, significant expansions within its pericentromeres, in some cases measuring hundreds of kilobases; these findings are in marked contrast to euchromatic segments in these species that exhibit only minor length changes. While plant pericentromeres do contain some duplications, we did not find evidence of extensive segmental duplications, as has been documented in primates. Our data support a model in which plant pericentromeres may experience selective pressures distinct from euchromatin, tolerating rapid, dynamic changes in structure and sequence content, including large insertions of mobile elements, 5S rDNA arrays and pseudogenes.

  16. Single-cell sequencing reveals karyotype heterogeneity in murine and human malignancies.

    PubMed

    Bakker, Bjorn; Taudt, Aaron; Belderbos, Mirjam E; Porubsky, David; Spierings, Diana C J; de Jong, Tristan V; Halsema, Nancy; Kazemier, Hinke G; Hoekstra-Wakker, Karina; Bradley, Allan; de Bont, Eveline S J M; van den Berg, Anke; Guryev, Victor; Lansdorp, Peter M; Colomé-Tatché, Maria; Foijer, Floris

    2016-05-31

    Chromosome instability leads to aneuploidy, a state in which cells have abnormal numbers of chromosomes, and is found in two out of three cancers. In a chromosomal instable p53 deficient mouse model with accelerated lymphomagenesis, we previously observed whole chromosome copy number changes affecting all lymphoma cells. This suggests that chromosome instability is somehow suppressed in the aneuploid lymphomas or that selection for frequently lost/gained chromosomes out-competes the CIN-imposed mis-segregation. To distinguish between these explanations and to examine karyotype dynamics in chromosome instable lymphoma, we use a newly developed single-cell whole genome sequencing (scWGS) platform that provides a complete and unbiased overview of copy number variations (CNV) in individual cells. To analyse these scWGS data, we develop AneuFinder, which allows annotation of copy number changes in a fully automated fashion and quantification of CNV heterogeneity between cells. Single-cell sequencing and AneuFinder analysis reveals high levels of copy number heterogeneity in chromosome instability-driven murine T-cell lymphoma samples, indicating ongoing chromosome instability. Application of this technology to human B cell leukaemias reveals different levels of karyotype heterogeneity in these cancers. Our data show that even though aneuploid tumours select for particular and recurring chromosome combinations, single-cell analysis using AneuFinder reveals copy number heterogeneity. This suggests ongoing chromosome instability that other platforms fail to detect. As chromosome instability might drive tumour evolution, karyotype analysis using single-cell sequencing technology could become an essential tool for cancer treatment stratification.

  17. Rewriting evolution--"been there, done that".

    PubMed

    Penny, David

    2013-01-01

    A recent paper by a science journalist in Nature shows major errors in understanding phylogenies, in this case of placental mammals. The underlying unrooted tree is probably correct, but the placement of the root just reflects a well-known error from the acceleration in the rate of evolution among some myomorph rodents.

  18. Whole-genome sequencing of staphylococcus haemolyticus uncovers the extreme plasticity of its genome and the evolution of human-colonizing staphylococcal species.

    PubMed

    Takeuchi, Fumihiko; Watanabe, Shinya; Baba, Tadashi; Yuzawa, Harumi; Ito, Teruyo; Morimoto, Yuh; Kuroda, Makoto; Cui, Longzhu; Takahashi, Mikio; Ankai, Akiho; Baba, Shin-ichi; Fukui, Shigehiro; Lee, Jean C; Hiramatsu, Keiichi

    2005-11-01

    Staphylococcus haemolyticus is an opportunistic bacterial pathogen that colonizes human skin and is remarkable for its highly antibiotic-resistant phenotype. We determined the complete genome sequence of S.haemolyticus to better understand its pathogenicity and evolutionary relatedness to the other staphylococcal species. A large proportion of the open reading frames in the genomes of S.haemolyticus, Staphylococcus aureus, and Staphylococcus epidermidis were conserved in their sequence and order on the chromosome. We identified a region of the bacterial chromosome just downstream of the origin of replication that showed little homology among the species but was conserved among strains within a species. This novel region, designated the "oriC environ," likely contributes to the evolution and differentiation of the staphylococcal species, since it was enriched for species-specific nonessential genes that contribute to the biological features of each staphylococcal species. A comparative analysis of the genomes of S.haemolyticus, S.aureus, and S.epidermidis elucidated differences in their biological and genetic characteristics and pathogenic potentials. We identified as many as 82 insertion sequences in the S.haemolyticus chromosome that probably mediated frequent genomic rearrangements, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its acquisition of antibiotic resistance.

  19. Whole-Genome Sequencing of Staphylococcus haemolyticus Uncovers the Extreme Plasticity of Its Genome and the Evolution of Human-Colonizing Staphylococcal Species

    PubMed Central

    Takeuchi, Fumihiko; Watanabe, Shinya; Baba, Tadashi; Yuzawa, Harumi; Ito, Teruyo; Morimoto, Yuh; Kuroda, Makoto; Cui, Longzhu; Takahashi, Mikio; Ankai, Akiho; Baba, Shin-ichi; Fukui, Shigehiro; Lee, Jean C.; Hiramatsu, Keiichi

    2005-01-01

    Staphylococcus haemolyticus is an opportunistic bacterial pathogen that colonizes human skin and is remarkable for its highly antibiotic-resistant phenotype. We determined the complete genome sequence of S.haemolyticus to better understand its pathogenicity and evolutionary relatedness to the other staphylococcal species. A large proportion of the open reading frames in the genomes of S.haemolyticus, Staphylococcus aureus, and Staphylococcus epidermidis were conserved in their sequence and order on the chromosome. We identified a region of the bacterial chromosome just downstream of the origin of replication that showed little homology among the species but was conserved among strains within a species. This novel region, designated the “oriC environ,” likely contributes to the evolution and differentiation of the staphylococcal species, since it was enriched for species-specific nonessential genes that contribute to the biological features of each staphylococcal species. A comparative analysis of the genomes of S.haemolyticus, S.aureus, and S.epidermidis elucidated differences in their biological and genetic characteristics and pathogenic potentials. We identified as many as 82 insertion sequences in the S.haemolyticus chromosome that probably mediated frequent genomic rearrangements, resulting in phenotypic diversification of the strain. Such rearrangements could have brought genomic plasticity to this species and contributed to its acquisition of antibiotic resistance. PMID:16237012

  20. Evolution models of helium white dwarf-main-sequence star merger remnants: the mass distribution of single low-mass white dwarfs

    NASA Astrophysics Data System (ADS)

    Zhang, Xianfei; Hall, Philip D.; Jeffery, C. Simon; Bi, Shaolan

    2018-02-01

    It is not known how single white dwarfs with masses less than 0.5Msolar -- low-mass white dwarfs -- are formed. One way in which such a white dwarf might be formed is after the merger of a helium-core white dwarf with a main-sequence star that produces a red giant branch star and fails to ignite helium. We use a stellar-evolution code to compute models of the remnants of these mergers and find a relation between the pre-merger masses and the final white dwarf mass. Combining our results with a model population, we predict that the mass distribution of single low-mass white dwarfs formed through this channel spans the range 0.37 to 0.5Msolar and peaks between 0.45 and 0.46Msolar. Helium white dwarf--main-sequence star mergers can also lead to the formation of single helium white dwarfs with masses up to 0.51Msolar. In our model the Galactic formation rate of single low-mass white dwarfs through this channel is about 8.7X10^-3yr^-1. Comparing our models with observations, we find that the majority of single low-mass white dwarfs (<0.5Msolar) are formed from helium white dwarf--main-sequence star mergers, at a rate which is about $2$ per cent of the total white dwarf formation rate.

  1. Sequence space and the ongoing expansion of the protein universe.

    PubMed

    Povolotskaya, Inna S; Kondrashov, Fyodor A

    2010-06-17

    The need to maintain the structural and functional integrity of an evolving protein severely restricts the repertoire of acceptable amino-acid substitutions. However, it is not known whether these restrictions impose a global limit on how far homologous protein sequences can diverge from each other. Here we explore the limits of protein evolution using sequence divergence data. We formulate a computational approach to study the rate of divergence of distant protein sequences and measure this rate for ancient proteins, those that were present in the last universal common ancestor. We show that ancient proteins are still diverging from each other, indicating an ongoing expansion of the protein sequence universe. The slow rate of this divergence is imposed by the sparseness of functional protein sequences in sequence space and the ruggedness of the protein fitness landscape: approximately 98 per cent of sites cannot accept an amino-acid substitution at any given moment but a vast majority of all sites may eventually be permitted to evolve when other, compensatory, changes occur. Thus, approximately 3.5 x 10(9) yr has not been enough to reach the limit of divergent evolution of proteins, and for most proteins the limit of sequence similarity imposed by common function may not exceed that of random sequences.

  2. Ultra-deep mutant spectrum profiling: improving sequencing accuracy using overlapping read pairs.

    PubMed

    Chen-Harris, Haiyin; Borucki, Monica K; Torres, Clinton; Slezak, Tom R; Allen, Jonathan E

    2013-02-12

    High throughput sequencing is beginning to make a transformative impact in the area of viral evolution. Deep sequencing has the potential to reveal the mutant spectrum within a viral sample at high resolution, thus enabling the close examination of viral mutational dynamics both within- and between-hosts. The challenge however, is to accurately model the errors in the sequencing data and differentiate real viral mutations, particularly those that exist at low frequencies, from sequencing errors. We demonstrate that overlapping read pairs (ORP) -- generated by combining short fragment sequencing libraries and longer sequencing reads -- significantly reduce sequencing error rates and improve rare variant detection accuracy. Using this sequencing protocol and an error model optimized for variant detection, we are able to capture a large number of genetic mutations present within a viral population at ultra-low frequency levels (<0.05%). Our rare variant detection strategies have important implications beyond viral evolution and can be applied to any basic and clinical research area that requires the identification of rare mutations.

  3. Inferring the evolution of the major histocompatibility complex of wild pigs and peccaries using hybridisation DNA capture-based sequencing.

    PubMed

    Lee, Carol; Moroldo, Marco; Perdomo-Sabogal, Alvaro; Mach, Núria; Marthey, Sylvain; Lecardonnel, Jérôme; Wahlberg, Per; Chong, Amanda Y; Estellé, Jordi; Ho, Simon Y W; Rogel-Gaillard, Claire; Gongora, Jaime

    2018-06-01

    The major histocompatibility complex (MHC) is a key genomic model region for understanding the evolution of gene families and the co-evolution between host and pathogen. To date, MHC studies have mostly focused on species from major vertebrate lineages. The evolution of MHC classical (Ia) and non-classical (Ib) genes in pigs has attracted interest because of their antigen presentation roles as part of the adaptive immune system. The pig family Suidae comprises over 18 extant species (mostly wild), but only the domestic pig has been extensively sequenced and annotated. To address this, we used a DNA-capture approach, with probes designed from the domestic pig genome, to generate MHC data for 11 wild species of pigs and their closest living family, Tayassuidae. The approach showed good efficiency for wild pigs (~80% reads mapped, ~87× coverage), compared to tayassuids (~12% reads mapped, ~4× coverage). We retrieved 145 MHC loci across both families. Phylogenetic analyses show that the class Ia and Ib genes underwent multiple duplications and diversifications before suids and tayassuids diverged from their common ancestor. The histocompatibility genes mostly form orthologous groups and there is genetic differentiation for most of these genes between Eurasian and sub-Saharan African wild pigs. Tests of selection showed that the peptide-binding region of class Ib genes was under positive selection. These findings contribute to better understanding of the evolutionary history of the MHC, specifically, the class I genes, and provide useful data for investigating the immune response of wild populations against pathogens.

  4. Delayed Gratification Habitable Zones (DG-HZs): When Deep Outer Solar System Regions Become Balmy During Post-Main Sequence Stellar Evolution

    NASA Astrophysics Data System (ADS)

    Stern, S. A.

    2002-09-01

    Late in the Sun's evolution it, like all low and moderate mass stars, it will burn as a red giant, generating 1000s of solar luminosities for a few tens of millions of years. A dozen years ago this stage of stellar evolution was predicted to create observable sublimation signatures in systems where Kuiper Belts (KBs) are extant (Stern et al. 1990, Nature, 345, 305); recently, the SWAS spacecraft detected such systems (Melnick et al. 2001, 412, 160). During the red giant phase, the habitable zone of our solar system will lie in the region where Triton, Pluto-Charon, and KBOs orbit. Compared to the 1 AU habitable zone where Earth resided early in the solar system's history, this "delayed gratification habitable zone (DG-HZ)" will enjoy a far less biologically hazardous environment-- with far lower harmful UV radiation levels from the Sun, and a far quieter collisional environment. Objects like Triton, Pluto-Charon, and KBOs, which are known to be rich in both water and organics, will then become possible sites for biochemical and perhaps even biological evolution. The Sun's DG-HZ may only be of academic interest owing to its great separation from us in time. However, several 108 approximately solar-type Milky Way stars burn as luminous red giants today. Thus, if icy-organic objects are common in the 20-50 AU zones of these stars, as they are in our solar system (and as inferred in numerous main sequence stellar disk systems), then DG-HZs form a kind of niche habitable zone that is likely to be numerically common in the galaxy. I will show the calculated temporal evolution of DG-HZs around various stellar types using modern stellar evolution luminosity tracks, and then discuss various aspects of DG-HZs, including the effects of stellar pulsations and mass loss winds. This work was supported by NASA's Origins of Solar Systems Program.

  5. MySSP: Non-stationary evolutionary sequence simulation, including indels

    PubMed Central

    Rosenberg, Michael S.

    2007-01-01

    MySSP is a new program for the simulation of DNA sequence evolution across a phylogenetic tree. Although many programs are available for sequence simulation, MySSP is unique in its inclusion of indels, flexibility in allowing for non-stationary patterns, and output of ancestral sequences. Some of these features can individually be found in existing programs, but have not all have been previously available in a single package. PMID:19325855

  6. Anchoring genome sequence to chromosomes of the central bearded dragon (Pogona vitticeps) enables reconstruction of ancestral squamate macrochromosomes and identifies sequence content of the Z chromosome.

    PubMed

    Deakin, Janine E; Edwards, Melanie J; Patel, Hardip; O'Meally, Denis; Lian, Jinmin; Stenhouse, Rachael; Ryan, Sam; Livernois, Alexandra M; Azad, Bhumika; Holleley, Clare E; Li, Qiye; Georges, Arthur

    2016-06-10

    Squamates (lizards and snakes) are a speciose lineage of reptiles displaying considerable karyotypic diversity, particularly among lizards. Understanding the evolution of this diversity requires comparison of genome organisation between species. Although the genomes of several squamate species have now been sequenced, only the green anole lizard has any sequence anchored to chromosomes. There is only limited gene mapping data available for five other squamates. This makes it difficult to reconstruct the events that have led to extant squamate karyotypic diversity. The purpose of this study was to anchor the recently sequenced central bearded dragon (Pogona vitticeps) genome to chromosomes to trace the evolution of squamate chromosomes. Assigning sequence to sex chromosomes was of particular interest for identifying candidate sex determining genes. By using two different approaches to map conserved blocks of genes, we were able to anchor approximately 42 % of the dragon genome sequence to chromosomes. We constructed detailed comparative maps between dragon, anole and chicken genomes, and where possible, made broader comparisons across Squamata using cytogenetic mapping information for five other species. We show that squamate macrochromosomes are relatively well conserved between species, supporting findings from previous molecular cytogenetic studies. Macrochromosome diversity between members of the Toxicofera clade has been generated by intrachromosomal, and a small number of interchromosomal, rearrangements. We reconstructed the ancestral squamate macrochromosomes by drawing upon comparative cytogenetic mapping data from seven squamate species and propose the events leading to the arrangements observed in representative species. In addition, we assigned over 8 Mbp of sequence containing 219 genes to the Z chromosome, providing a list of genes to begin testing as candidate sex determining genes. Anchoring of the dragon genome has provided substantial insight into

  7. Protein Science by DNA Sequencing: How Advances in Molecular Biology Are Accelerating Biochemistry.

    PubMed

    Higgins, Sean A; Savage, David F

    2018-01-09

    A fundamental goal of protein biochemistry is to determine the sequence-function relationship, but the vastness of sequence space makes comprehensive evaluation of this landscape difficult. However, advances in DNA synthesis and sequencing now allow researchers to assess the functional impact of every single mutation in many proteins, but challenges remain in library construction and the development of general assays applicable to a diverse range of protein functions. This Perspective briefly outlines the technical innovations in DNA manipulation that allow massively parallel protein biochemistry and then summarizes the methods currently available for library construction and the functional assays of protein variants. Areas in need of future innovation are highlighted with a particular focus on assay development and the use of computational analysis with machine learning to effectively traverse the sequence-function landscape. Finally, applications in the fundamentals of protein biochemistry, disease prediction, and protein engineering are presented.

  8. The evolution of vertebrate Toll-like receptors

    USGS Publications Warehouse

    Roach, J.C.; Glusman, G.; Rowen, L.; Kaur, A.; Purcell, M.K.; Smith, K.D.; Hood, L.E.; Aderem, A.

    2005-01-01

    The complete sequences of Takifugu Toll-like receptor (TLR) loci and gene predictions from many draft genomes enable comprehensive molecular phylogenetic analysis. Strong selective pressure for recognition of and response to pathogen-associated molecular patterns has maintained a largely unchanging TLR recognition in all vertebrates. There are six major families of vertebrate TLRs. This repertoire is distinct from that of invertebrates. TLRs within a family recognize a general class of pathogen-associated molecular patterns. Most vertebrates have exactly one gene ortholog for each TLR family. The family including TLR1 has more species-specific adaptations than other families. A major family including TLR11 is represented in humans only by a pseudogene. Coincidental evolution plays a minor role in TLR evolution. The sequencing phase of this study produced finished genomic sequences for the 12 Takifugu rubripes TLRs. In addition, we have produced > 70 gene models, including sequences from the opossum, chicken, frog, dog, sea urchin, and sea squirt. ?? 2005 by The National Academy of Sciences of the USA.

  9. An experimental and computational evolution-based method to study a mode of co-evolution of overlapping open reading frames in the AAV2 viral genome.

    PubMed

    Kawano, Yasuhiro; Neeley, Shane; Adachi, Kei; Nakai, Hiroyuki

    2013-01-01

    Overlapping open reading frames (ORFs) in viral genomes undergo co-evolution; however, how individual amino acids coded by overlapping ORFs are structurally, functionally, and co-evolutionarily constrained remains difficult to address by conventional homologous sequence alignment approaches. We report here a new experimental and computational evolution-based methodology to address this question and report its preliminary application to elucidating a mode of co-evolution of the frame-shifted overlapping ORFs in the adeno-associated virus (AAV) serotype 2 viral genome. These ORFs encode both capsid VP protein and non-structural assembly-activating protein (AAP). To show proof of principle of the new method, we focused on the evolutionarily conserved QVKEVTQ and KSKRSRR motifs, a pair of overlapping heptapeptides in VP and AAP, respectively. In the new method, we first identified a large number of capsid-forming VP3 mutants and functionally competent AAP mutants of these motifs from mutant libraries by experimental directed evolution under no co-evolutionary constraints. We used Illumina sequencing to obtain a large dataset and then statistically assessed the viability of VP and AAP heptapeptide mutants. The obtained heptapeptide information was then integrated into an evolutionary algorithm, with which VP and AAP were co-evolved from random or native nucleotide sequences in silico. As a result, we demonstrate that these two heptapeptide motifs could exhibit high degeneracy if coded by separate nucleotide sequences, and elucidate how overlap-evoked co-evolutionary constraints play a role in making the VP and AAP heptapeptide sequences into the present shape. Specifically, we demonstrate that two valine (V) residues and β-strand propensity in QVKEVTQ are structurally important, the strongly negative and hydrophilic nature of KSKRSRR is functionally important, and overlap-evoked co-evolution imposes strong constraints on serine (S) residues in KSKRSRR, despite high

  10. Nondegenerative Evolution in Ancient Heritable Bacterial Endosymbionts of Fungi.

    PubMed

    Mondo, Stephen J; Salvioli, Alessandra; Bonfante, Paola; Morton, Joseph B; Pawlowska, Teresa E

    2016-09-01

    Bacterial endosymbionts are critical to the existence of many eukaryotes. Among them, vertically transmitted endobacteria are uniquely typified by reduced genomes and molecular evolution rate acceleration relative to free-living taxa. These patterns are attributable to genetic drift-dominated degenerative processes associated with reproductive dependence on the host. The degenerative evolution scenario is well supported in endobacteria with strict vertical transmission, such as essential mutualists of insects. In contrast, heritable endosymbionts that are nonessential to their hosts and engage occasionally in horizontal transmission are expected to display deviations from the degenerative evolution model. To explore evolution patterns in such nonessential endobacteria, we focused on Candidatus Glomeribacter gigasporarum ancient heritable mutualists of fungi. Using a collection of genomes, we estimated in Glomeribacter mutation rate at 2.03 × 10(-9) substitutions per site per year and effective population size at 1.44 × 10(8) Both fall within the range of values observed in free-living bacteria. To assess the ability of Glomeribacter to purge slightly deleterious mutations, we examined genome-wide dN/dS values and distribution patterns. We found that these dN/dS profiles cluster Glomeribacter with free-living bacteria as well as with other nonessential endosymbionts, while distinguishing it from essential heritable mutualists of insects. Finally, our evolutionary simulations revealed that the molecular evolution rate acceleration in Glomeribacter is caused by limited recombination in a largely clonal population rather than by increased fixation of slightly deleterious mutations. Based on these patterns, we propose that genome evolution in Glomeribacter is nondegenerative and exemplifies a departure from the model of degenerative evolution in heritable endosymbionts. © The Author 2016. Published by Oxford University Press on behalf of the Society for

  11. AIR-MRF: Accelerated iterative reconstruction for magnetic resonance fingerprinting.

    PubMed

    Cline, Christopher C; Chen, Xiao; Mailhe, Boris; Wang, Qiu; Pfeuffer, Josef; Nittka, Mathias; Griswold, Mark A; Speier, Peter; Nadar, Mariappan S

    2017-09-01

    Existing approaches for reconstruction of multiparametric maps with magnetic resonance fingerprinting (MRF) are currently limited by their estimation accuracy and reconstruction time. We aimed to address these issues with a novel combination of iterative reconstruction, fingerprint compression, additional regularization, and accelerated dictionary search methods. The pipeline described here, accelerated iterative reconstruction for magnetic resonance fingerprinting (AIR-MRF), was evaluated with simulations as well as phantom and in vivo scans. We found that the AIR-MRF pipeline provided reduced parameter estimation errors compared to non-iterative and other iterative methods, particularly at shorter sequence lengths. Accelerated dictionary search methods incorporated into the iterative pipeline reduced the reconstruction time at little cost of quality. Copyright © 2017 Elsevier Inc. All rights reserved.

  12. Comparative analysis of complete chloroplast genome sequence and inversion variation in Lasthenia burkei (Madieae, Asteraceae).

    PubMed

    Walker, Joseph F; Zanis, Michael J; Emery, Nancy C

    2014-04-01

    Complete chloroplast genome studies can help resolve relationships among large, complex plant lineages such as Asteraceae. We present the first whole plastome from the Madieae tribe and compare its sequence variation to other chloroplast genomes in Asteraceae. We used high throughput sequencing to obtain the Lasthenia burkei chloroplast genome. We compared sequence structure and rates of molecular evolution in the small single copy (SSC), large single copy (LSC), and inverted repeat (IR) regions to those for eight Asteraceae accessions and one Solanaceae accession. The chloroplast sequence of L. burkei is 150 746 bp and contains 81 unique protein coding genes and 4 coding ribosomal RNA sequences. We identified three major inversions in the L. burkei chloroplast, all of which have been found in other Asteraceae lineages, and a previously unreported inversion in Lactuca sativa. Regions flanking inversions contained tRNA sequences, but did not have particularly high G + C content. Substitution rates varied among the SSC, LSC, and IR regions, and rates of evolution within each region varied among species. Some observed differences in rates of molecular evolution may be explained by the relative proportion of coding to noncoding sequence within regions. Rates of molecular evolution vary substantially within and among chloroplast genomes, and major inversion events may be promoted by the presence of tRNAs. Collectively, these results provide insight into different mechanisms that may promote intramolecular recombination and the inversion of large genomic regions in the plastome.

  13. Sequencing and comparing whole mitochondrial genomes ofanimals

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Boore, Jeffrey L.; Macey, J. Robert; Medina, Monica

    2005-04-22

    Comparing complete animal mitochondrial genome sequences is becoming increasingly common for phylogenetic reconstruction and as a model for genome evolution. Not only are they much more informative than shorter sequences of individual genes for inferring evolutionary relatedness, but these data also provide sets of genome-level characters, such as the relative arrangements of genes, that can be especially powerful. We describe here the protocols commonly used for physically isolating mtDNA, for amplifying these by PCR or RCA, for cloning,sequencing, assembly, validation, and gene annotation, and for comparing both sequences and gene arrangements. On several topics, we offer general observations based onmore » our experiences to date with determining and comparing complete mtDNA sequences.« less

  14. Accelerated Gene Evolution and Subfunctionalization in thePseudotetraploid Frog Xenopus Laevis

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Hellsten, Uffe; Khokha, Mustafa K.; Grammar, Timothy C.

    2007-03-01

    Ancient whole genome duplications have been implicated in the vertebrate and teleost radiations, and in the emergence of diverse angiosperm lineages, but the evolutionary response to such a perturbation is still poorly understood. The African clawed frog Xenopus laevis experienced a relatively recent tetraploidization {approx} 40 million years ago. Analysis of the considerable amount of EST sequence available for this species together with the genome sequence of the related diploid Xenopus tropicalis provides a unique opportunity to study the genomic response to whole genome duplication.

  15. Diversity, Distribution, and Evolution of Tomato Viruses in China Uncovered by Small RNA Sequencing

    PubMed Central

    Xu, Chenxi; Taylor, Angela; Jiao, Chen; Xu, Yimin; Cai, Xiaofeng; Wang, Xiaoli; Ge, Chenhui; Pan, Guanghui; Wang, Quanxi

    2017-01-01

    ABSTRACT Tomato is a major vegetable crop that has tremendous popularity. However, viral disease is still a major factor limiting tomato production. Here, we report the tomato virome identified through sequencing small RNAs of 170 field-grown samples collected in China. A total of 22 viruses were identified, including both well-documented and newly detected viruses. The tomato viral community is dominated by a few species, and they exhibit polymorphisms and recombination in the genomes with cold spots and hot spots. Most samples were coinfected by multiple viruses, and the majority of identified viruses are positive-sense single-stranded RNA viruses. Evolutionary analysis of one of the most dominant tomato viruses, Tomato yellow leaf curl virus (TYLCV), predicts its origin and the time back to its most recent common ancestor. The broadly sampled data have enabled us to identify several unreported viruses in tomato, including a completely new virus, which has a genome of ∼13.4 kb and groups with aphid-transmitted viruses in the genus Cytorhabdovirus. Although both DNA and RNA viruses can trigger the biogenesis of virus-derived small interfering RNAs (vsiRNAs), we show that features such as length distribution, paired distance, and base selection bias of vsiRNA sequences reflect different plant Dicer-like proteins and Argonautes involved in vsiRNA biogenesis. Collectively, this study offers insights into host-virus interaction in tomato and provides valuable information to facilitate the management of viral diseases. IMPORTANCE Tomato is an important source of micronutrients in the human diet and is extensively consumed around the world. Virus is among the major constraints on tomato production. Categorizing virus species that are capable of infecting tomato and understanding their diversity and evolution are challenging due to difficulties in detecting such fast-evolving biological entities. Here, we report the landscape of the tomato virome in China, the leading

  16. Diversity, Distribution, and Evolution of Tomato Viruses in China Uncovered by Small RNA Sequencing.

    PubMed

    Xu, Chenxi; Sun, Xuepeng; Taylor, Angela; Jiao, Chen; Xu, Yimin; Cai, Xiaofeng; Wang, Xiaoli; Ge, Chenhui; Pan, Guanghui; Wang, Quanxi; Fei, Zhangjun; Wang, Quanhua

    2017-06-01

    Tomato is a major vegetable crop that has tremendous popularity. However, viral disease is still a major factor limiting tomato production. Here, we report the tomato virome identified through sequencing small RNAs of 170 field-grown samples collected in China. A total of 22 viruses were identified, including both well-documented and newly detected viruses. The tomato viral community is dominated by a few species, and they exhibit polymorphisms and recombination in the genomes with cold spots and hot spots. Most samples were coinfected by multiple viruses, and the majority of identified viruses are positive-sense single-stranded RNA viruses. Evolutionary analysis of one of the most dominant tomato viruses, Tomato yellow leaf curl virus (TYLCV), predicts its origin and the time back to its most recent common ancestor. The broadly sampled data have enabled us to identify several unreported viruses in tomato, including a completely new virus, which has a genome of ∼13.4 kb and groups with aphid-transmitted viruses in the genus Cytorhabdovirus Although both DNA and RNA viruses can trigger the biogenesis of virus-derived small interfering RNAs (vsiRNAs), we show that features such as length distribution, paired distance, and base selection bias of vsiRNA sequences reflect different plant Dicer-like proteins and Argonautes involved in vsiRNA biogenesis. Collectively, this study offers insights into host-virus interaction in tomato and provides valuable information to facilitate the management of viral diseases. IMPORTANCE Tomato is an important source of micronutrients in the human diet and is extensively consumed around the world. Virus is among the major constraints on tomato production. Categorizing virus species that are capable of infecting tomato and understanding their diversity and evolution are challenging due to difficulties in detecting such fast-evolving biological entities. Here, we report the landscape of the tomato virome in China, the leading country in

  17. Function and regulation of AUTS2, a gene implicated in autism and human evolution.

    PubMed

    Oksenberg, Nir; Stevison, Laurie; Wall, Jeffrey D; Ahituv, Nadav

    2013-01-01

    Nucleotide changes in the AUTS2 locus, some of which affect only noncoding regions, are associated with autism and other neurological disorders, including attention deficit hyperactivity disorder, epilepsy, dyslexia, motor delay, language delay, visual impairment, microcephaly, and alcohol consumption. In addition, AUTS2 contains the most significantly accelerated genomic region differentiating humans from Neanderthals, which is primarily composed of noncoding variants. However, the function and regulation of this gene remain largely unknown. To characterize auts2 function, we knocked it down in zebrafish, leading to a smaller head size, neuronal reduction, and decreased mobility. To characterize AUTS2 regulatory elements, we tested sequences for enhancer activity in zebrafish and mice. We identified 23 functional zebrafish enhancers, 10 of which were active in the brain. Our mouse enhancer assays characterized three mouse brain enhancers that overlap an ASD-associated deletion and four mouse enhancers that reside in regions implicated in human evolution, two of which are active in the brain. Combined, our results show that AUTS2 is important for neurodevelopment and expose candidate enhancer sequences in which nucleotide variation could lead to neurological disease and human-specific traits.

  18. Dynamics of actin evolution in dinoflagellates.

    PubMed

    Kim, Sunju; Bachvaroff, Tsvetan R; Handy, Sara M; Delwiche, Charles F

    2011-04-01

    Dinoflagellates have unique nuclei and intriguing genome characteristics with very high DNA content making complete genome sequencing difficult. In dinoflagellates, many genes are found in multicopy gene families, but the processes involved in the establishment and maintenance of these gene families are poorly understood. Understanding the dynamics of gene family evolution in dinoflagellates requires comparisons at different evolutionary scales. Studies of closely related species provide fine-scale information relative to species divergence, whereas comparisons of more distantly related species provides broad context. We selected the actin gene family as a highly expressed conserved gene previously studied in dinoflagellates. Of the 142 sequences determined in this study, 103 were from the two closely related species, Dinophysis acuminata and D. caudata, including full length and partial cDNA sequences as well as partial genomic amplicons. For these two Dinophysis species, at least three types of sequences could be identified. Most copies (79%) were relatively similar and in nucleotide trees, the sequences formed two bushy clades corresponding to the two species. In comparisons within species, only eight to ten nucleotide differences were found between these copies. The two remaining types formed clades containing sequences from both species. One type included the most similar sequences in between-species comparisons with as few as 12 nucleotide differences between species. The second type included the most divergent sequences in comparisons between and within species with up to 93 nucleotide differences between sequences. In all the sequences, most variation occurred in synonymous sites or the 5' UnTranslated Region (UTR), although there was still limited amino acid variation between most sequences. Several potential pseudogenes were found (approximately 10% of all sequences depending on species) with incomplete open reading frames due to frameshifts or early stop

  19. The challenges of sequencing by synthesis.

    PubMed

    Fuller, Carl W; Middendorf, Lyle R; Benner, Steven A; Church, George M; Harris, Timothy; Huang, Xiaohua; Jovanovich, Stevan B; Nelson, John R; Schloss, Jeffery A; Schwartz, David C; Vezenov, Dmitri V

    2009-11-01

    DNA sequencing-by-synthesis (SBS) technology, using a polymerase or ligase enzyme as its core biochemistry, has already been incorporated in several second-generation DNA sequencing systems with significant performance. Notwithstanding the substantial success of these SBS platforms, challenges continue to limit the ability to reduce the cost of sequencing a human genome to $100,000 or less. Achieving dramatically reduced cost with enhanced throughput and quality will require the seamless integration of scientific and technological effort across disciplines within biochemistry, chemistry, physics and engineering. The challenges include sample preparation, surface chemistry, fluorescent labels, optimizing the enzyme-substrate system, optics, instrumentation, understanding tradeoffs of throughput versus accuracy, and read-length/phasing limitations. By framing these challenges in a manner accessible to a broad community of scientists and engineers, we hope to solicit input from the broader research community on means of accelerating the advancement of genome sequencing technology.

  20. EventThread: Visual Summarization and Stage Analysis of Event Sequence Data.

    PubMed

    Guo, Shunan; Xu, Ke; Zhao, Rongwen; Gotz, David; Zha, Hongyuan; Cao, Nan

    2018-01-01

    Event sequence data such as electronic health records, a person's academic records, or car service records, are ordered series of events which have occurred over a period of time. Analyzing collections of event sequences can reveal common or semantically important sequential patterns. For example, event sequence analysis might reveal frequently used care plans for treating a disease, typical publishing patterns of professors, and the patterns of service that result in a well-maintained car. It is challenging, however, to visually explore large numbers of event sequences, or sequences with large numbers of event types. Existing methods focus on extracting explicitly matching patterns of events using statistical analysis to create stages of event progression over time. However, these methods fail to capture latent clusters of similar but not identical evolutions of event sequences. In this paper, we introduce a novel visualization system named EventThread which clusters event sequences into threads based on tensor analysis and visualizes the latent stage categories and evolution patterns by interactively grouping the threads by similarity into time-specific clusters. We demonstrate the effectiveness of EventThread through usage scenarios in three different application domains and via interviews with an expert user.

  1. Chemoresistance Evolution in Triple-Negative Breast Cancer Delineated by Single-Cell Sequencing.

    PubMed

    Kim, Charissa; Gao, Ruli; Sei, Emi; Brandt, Rachel; Hartman, Johan; Hatschek, Thomas; Crosetto, Nicola; Foukakis, Theodoros; Navin, Nicholas E

    2018-05-03

    Triple-negative breast cancer (TNBC) is an aggressive subtype that frequently develops resistance to chemotherapy. An unresolved question is whether resistance is caused by the selection of rare pre-existing clones or alternatively through the acquisition of new genomic aberrations. To investigate this question, we applied single-cell DNA and RNA sequencing in addition to bulk exome sequencing to profile longitudinal samples from 20 TNBC patients during neoadjuvant chemotherapy (NAC). Deep-exome sequencing identified 10 patients in which NAC led to clonal extinction and 10 patients in which clones persisted after treatment. In 8 patients, we performed a more detailed study using single-cell DNA sequencing to analyze 900 cells and single-cell RNA sequencing to analyze 6,862 cells. Our data showed that resistant genotypes were pre-existing and adaptively selected by NAC, while transcriptional profiles were acquired by reprogramming in response to chemotherapy in TNBC patients. Copyright © 2018 Elsevier Inc. All rights reserved.

  2. Sequence Memory Constraints Give Rise to Language-Like Structure through Iterated Learning

    PubMed Central

    Cornish, Hannah; Dale, Rick; Kirby, Simon; Christiansen, Morten H.

    2017-01-01

    Human language is composed of sequences of reusable elements. The origins of the sequential structure of language is a hotly debated topic in evolutionary linguistics. In this paper, we show that sets of sequences with language-like statistical properties can emerge from a process of cultural evolution under pressure from chunk-based memory constraints. We employ a novel experimental task that is non-linguistic and non-communicative in nature, in which participants are trained on and later asked to recall a set of sequences one-by-one. Recalled sequences from one participant become training data for the next participant. In this way, we simulate cultural evolution in the laboratory. Our results show a cumulative increase in structure, and by comparing this structure to data from existing linguistic corpora, we demonstrate a close parallel between the sets of sequences that emerge in our experiment and those seen in natural language. PMID:28118370

  3. Sequence Memory Constraints Give Rise to Language-Like Structure through Iterated Learning.

    PubMed

    Cornish, Hannah; Dale, Rick; Kirby, Simon; Christiansen, Morten H

    2017-01-01

    Human language is composed of sequences of reusable elements. The origins of the sequential structure of language is a hotly debated topic in evolutionary linguistics. In this paper, we show that sets of sequences with language-like statistical properties can emerge from a process of cultural evolution under pressure from chunk-based memory constraints. We employ a novel experimental task that is non-linguistic and non-communicative in nature, in which participants are trained on and later asked to recall a set of sequences one-by-one. Recalled sequences from one participant become training data for the next participant. In this way, we simulate cultural evolution in the laboratory. Our results show a cumulative increase in structure, and by comparing this structure to data from existing linguistic corpora, we demonstrate a close parallel between the sets of sequences that emerge in our experiment and those seen in natural language.

  4. Different evolutionary patterns of SNPs between domains and unassigned regions in human protein-coding sequences.

    PubMed

    Pang, Erli; Wu, Xiaomei; Lin, Kui

    2016-06-01

    Protein evolution plays an important role in the evolution of each genome. Because of their functional nature, in general, most of their parts or sites are differently constrained selectively, particularly by purifying selection. Most previous studies on protein evolution considered individual proteins in their entirety or compared protein-coding sequences with non-coding sequences. Less attention has been paid to the evolution of different parts within each protein of a given genome. To this end, based on PfamA annotation of all human proteins, each protein sequence can be split into two parts: domains or unassigned regions. Using this rationale, single nucleotide polymorphisms (SNPs) in protein-coding sequences from the 1000 Genomes Project were mapped according to two classifications: SNPs occurring within protein domains and those within unassigned regions. With these classifications, we found: the density of synonymous SNPs within domains is significantly greater than that of synonymous SNPs within unassigned regions; however, the density of non-synonymous SNPs shows the opposite pattern. We also found there are signatures of purifying selection on both the domain and unassigned regions. Furthermore, the selective strength on domains is significantly greater than that on unassigned regions. In addition, among all of the human protein sequences, there are 117 PfamA domains in which no SNPs are found. Our results highlight an important aspect of protein domains and may contribute to our understanding of protein evolution.

  5. DNA barcodes for ecology, evolution, and conservation.

    PubMed

    Kress, W John; García-Robledo, Carlos; Uriarte, Maria; Erickson, David L

    2015-01-01

    The use of DNA barcodes, which are short gene sequences taken from a standardized portion of the genome and used to identify species, is entering a new phase of application as more and more investigations employ these genetic markers to address questions relating to the ecology and evolution of natural systems. The suite of DNA barcode markers now applied to specific taxonomic groups of organisms are proving invaluable for understanding species boundaries, community ecology, functional trait evolution, trophic interactions, and the conservation of biodiversity. The application of next-generation sequencing (NGS) technology will greatly expand the versatility of DNA barcodes across the Tree of Life, habitats, and geographies as new methodologies are explored and developed. Published by Elsevier Ltd.

  6. Detecting Selection on Protein Stability through Statistical Mechanical Models of Folding and Evolution

    PubMed Central

    Bastolla, Ugo

    2014-01-01

    The properties of biomolecules depend both on physics and on the evolutionary process that formed them. These two points of view produce a powerful synergism. Physics sets the stage and the constraints that molecular evolution has to obey, and evolutionary theory helps in rationalizing the physical properties of biomolecules, including protein folding thermodynamics. To complete the parallelism, protein thermodynamics is founded on the statistical mechanics in the space of protein structures, and molecular evolution can be viewed as statistical mechanics in the space of protein sequences. In this review, we will integrate both points of view, applying them to detecting selection on the stability of the folded state of proteins. We will start discussing positive design, which strengthens the stability of the folded against the unfolded state of proteins. Positive design justifies why statistical potentials for protein folding can be obtained from the frequencies of structural motifs. Stability against unfolding is easier to achieve for longer proteins. On the contrary, negative design, which consists in destabilizing frequently formed misfolded conformations, is more difficult to achieve for longer proteins. The folding rate can be enhanced by strengthening short-range native interactions, but this requirement contrasts with negative design, and evolution has to trade-off between them. Finally, selection can accelerate functional movements by favoring low frequency normal modes of the dynamics of the native state that strongly correlate with the functional conformation change. PMID:24970217

  7. Mean-state acceleration of cloud-resolving models and large eddy simulations

    DOE PAGES

    Jones, C. R.; Bretherton, C. S.; Pritchard, M. S.

    2015-10-29

    In this study, large eddy simulations and cloud-resolving models (CRMs) are routinely used to simulate boundary layer and deep convective cloud processes, aid in the development of moist physical parameterization for global models, study cloud-climate feedbacks and cloud-aerosol interaction, and as the heart of superparameterized climate models. These models are computationally demanding, placing practical constraints on their use in these applications, especially for long, climate-relevant simulations. In many situations, the horizontal-mean atmospheric structure evolves slowly compared to the turnover time of the most energetic turbulent eddies. We develop a simple scheme to reduce this time scale separation to accelerate themore » evolution of the mean state. Using this approach we are able to accelerate the model evolution by a factor of 2–16 or more in idealized stratocumulus, shallow and deep cumulus convection without substantial loss of accuracy in simulating mean cloud statistics and their sensitivity to climate change perturbations. As a culminating test, we apply this technique to accelerate the embedded CRMs in the Superparameterized Community Atmosphere Model by a factor of 2, thereby showing that the method is robust and stable to realistic perturbations across spatial and temporal scales typical in a GCM.« less

  8. Shedding new light on opsin evolution

    PubMed Central

    Porter, Megan L.; Blasic, Joseph R.; Bok, Michael J.; Cameron, Evan G.; Pringle, Thomas; Cronin, Thomas W.; Robinson, Phyllis R.

    2012-01-01

    Opsin proteins are essential molecules in mediating the ability of animals to detect and use light for diverse biological functions. Therefore, understanding the evolutionary history of opsins is key to understanding the evolution of light detection and photoreception in animals. As genomic data have appeared and rapidly expanded in quantity, it has become possible to analyse opsins that functionally and histologically are less well characterized, and thus to examine opsin evolution strictly from a genetic perspective. We have incorporated these new data into a large-scale, genome-based analysis of opsin evolution. We use an extensive phylogeny of currently known opsin sequence diversity as a foundation for examining the evolutionary distributions of key functional features within the opsin clade. This new analysis illustrates the lability of opsin protein-expression patterns, site-specific functionality (i.e. counterion position) and G-protein binding interactions. Further, it demonstrates the limitations of current model organisms, and highlights the need for further characterization of many of the opsin sequence groups with unknown function. PMID:22012981

  9. Solar wind conditions leading to efficient radiation belt electron acceleration: A superposed epoch analysis

    DOE PAGES

    Li, W.; Thorne, R. M.; Bortnik, J.; ...

    2015-09-07

    In this study by determining preferential solar wind conditions leading to efficient radiation belt electron acceleration is crucial for predicting radiation belt electron dynamics. Using Van Allen Probes electron observations (>1 MeV) from 2012 to 2015, we identify a number of efficient and inefficient acceleration events separately to perform a superposed epoch analysis of the corresponding solar wind parameters and geomagnetic indices. By directly comparing efficient and inefficient acceleration events, we clearly show that prolonged southward Bz, high solar wind speed, and low dynamic pressure are critical for electron acceleration to >1 MeV energies in the heart of the outermore » radiation belt. We also evaluate chorus wave evolution using the superposed epoch analysis for the identified efficient and inefficient acceleration events and find that chorus wave intensity is much stronger and lasts longer during efficient electron acceleration events, supporting the scenario that chorus waves play a key role in MeV electron acceleration.« less

  10. Relaxed Evolution in the Tyrosine Aminotransferase Gene Tat in Old World Fruit Bats (Chiroptera: Pteropodidae)

    PubMed Central

    Shen, Bin; Fang, Tao; Yang, Tianxiao; Jones, Gareth; Irwin, David M.; Zhang, Shuyi

    2014-01-01

    Frugivorous and nectarivorous bats fuel their metabolism mostly by using carbohydrates and allocate the restricted amounts of ingested proteins mainly for anabolic protein syntheses rather than for catabolic energy production. Thus, it is possible that genes involved in protein (amino acid) catabolism may have undergone relaxed evolution in these fruit- and nectar-eating bats. The tyrosine aminotransferase (TAT, encoded by the Tat gene) is the rate-limiting enzyme in the tyrosine catabolic pathway. To test whether the Tat gene has undergone relaxed evolution in the fruit- and nectar-eating bats, we obtained the Tat coding region from 20 bat species including four Old World fruit bats (Pteropodidae) and two New World fruit bats (Phyllostomidae). Phylogenetic reconstructions revealed a gene tree in which all echolocating bats (including the New World fruit bats) formed a monophyletic group. The phylogenetic conflict appears to stem from accelerated TAT protein sequence evolution in the Old World fruit bats. Our molecular evolutionary analyses confirmed a change in the selection pressure acting on Tat, which was likely caused by a relaxation of the evolutionary constraints on the Tat gene in the Old World fruit bats. Hepatic TAT activity assays showed that TAT activities in species of the Old World fruit bats are significantly lower than those of insectivorous bats and omnivorous mice, which was not caused by a change in TAT protein levels in the liver. Our study provides unambiguous evidence that the Tat gene has undergone relaxed evolution in the Old World fruit bats in response to changes in their metabolism due to the evolution of their special diet. PMID:24824435

  11. Evolution of prokaryote and eukaryote lines inferred from sequence evidence

    NASA Technical Reports Server (NTRS)

    Hunt, L. T.; George, D. G.; Yeh, L.-S.; Dayhoff, M. O.

    1984-01-01

    This paper describes the evolution of prokaryotes and early eukaryotes, including their symbiotic relationships, as inferred from phylogenetic trees of bacterial ferredoxin, 5S ribosomal RNA, ribulose-1,5-biphosphate carboxylase large chain, and mitochondrial cytochrome oxidase polypeptide II.

  12. Time Recovery for a Complex Process Using Accelerated Dynamics.

    PubMed

    Paz, S Alexis; Leiva, Ezequiel P M

    2015-04-14

    The hyperdynamics method (HD) developed by Voter (J. Chem. Phys. 1996, 106, 4665) sets the theoretical basis to construct an accelerated simulation scheme that holds the time scale information. Since HD is based on transition state theory, pseudoequilibrium conditions (PEC) must be satisfied before any system in a trapped state may be accelerated. As the system evolves, many trapped states may appear, and the PEC must be assumed in each one to accelerate the escape. However, since the system evolution is a priori unknown, the PEC cannot be permanently assumed to be true. Furthermore, the different parameters of the bias function used may need drastic recalibration during this evolution. To overcome these problems, we present a general scheme to switch between HD and conventional molecular dynamics (MD) in an automatic fashion during the simulation. To decide when HD should start and finish, criteria based on the energetic properties of the system are introduced. On the other hand, a very simple bias function is proposed, leading to a straightforward on-the-fly set up of the required parameters. A way to measure the quality of the simulation is suggested. The efficiency of the present hybrid HD-MD method is tested for a two-dimensional model potential and for the coalescence process of two nanoparticles. In spite of the important complexity of the latter system (165 degrees of freedoms), some relevant mechanistic properties were recovered within the present method.

  13. Epistasis in protein evolution

    PubMed Central

    Starr, Tyler N.

    2016-01-01

    Abstract The structure, function, and evolution of proteins depend on physical and genetic interactions among amino acids. Recent studies have used new strategies to explore the prevalence, biochemical mechanisms, and evolutionary implications of these interactions—called epistasis—within proteins. Here we describe an emerging picture of pervasive epistasis in which the physical and biological effects of mutations change over the course of evolution in a lineage‐specific fashion. Epistasis can restrict the trajectories available to an evolving protein or open new paths to sequences and functions that would otherwise have been inaccessible. We describe two broad classes of epistatic interactions, which arise from different physical mechanisms and have different effects on evolutionary processes. Specific epistasis—in which one mutation influences the phenotypic effect of few other mutations—is caused by direct and indirect physical interactions between mutations, which nonadditively change the protein's physical properties, such as conformation, stability, or affinity for ligands. In contrast, nonspecific epistasis describes mutations that modify the effect of many others; these typically behave additively with respect to the physical properties of a protein but exhibit epistasis because of a nonlinear relationship between the physical properties and their biological effects, such as function or fitness. Both types of interaction are rampant, but specific epistasis has stronger effects on the rate and outcomes of evolution, because it imposes stricter constraints and modulates evolutionary potential more dramatically; it therefore makes evolution more contingent on low‐probability historical events and leaves stronger marks on the sequences, structures, and functions of protein families. PMID:26833806

  14. Faster-X evolution of gene expression is driven by recessive adaptive cis-regulatory variation in Drosophila.

    PubMed

    Llopart, Ana

    2018-05-01

    The hemizygosity of the X (Z) chromosome fully exposes the fitness effects of mutations on that chromosome and has evolutionary consequences on the relative rates of evolution of X and autosomes. Specifically, several population genetics models predict increased rates of evolution in X-linked loci relative to autosomal loci. This prediction of faster-X evolution has been evaluated and confirmed for both protein coding sequences and gene expression. In the case of faster-X evolution for gene expression divergence, it is often assumed that variation in 5' noncoding sequences is associated with variation in transcript abundance between species but a formal, genomewide test of this hypothesis is still missing. Here, I use whole genome sequence data in Drosophila yakuba and D. santomea to evaluate this hypothesis and report positive correlations between sequence divergence at 5' noncoding sequences and gene expression divergence. I also examine polymorphism and divergence in 9,279 noncoding sequences located at the 5' end of annotated genes and detected multiple signals of positive selection. Notably, I used the traditional synonymous sites as neutral reference to test for adaptive evolution, but I also used bases 8-30 of introns <65 bp, which have been proposed to be a better neutral choice. X-linked genes with high degree of male-biased expression show the most extreme adaptive pattern at 5' noncoding regions, in agreement with faster-X evolution for gene expression divergence and a higher incidence of positively selected recessive mutations. © 2018 The Authors. Molecular Ecology Published by John Wiley & Sons Ltd.

  15. The organization and evolution of the Responder satellite in species of the Drosophila melanogaster group: dynamic evolution of a target of meiotic drive.

    PubMed

    Larracuente, Amanda M

    2014-11-25

    Satellite DNA can make up a substantial fraction of eukaryotic genomes and has roles in genome structure and chromosome segregation. The rapid evolution of satellite DNA can contribute to genomic instability and genetic incompatibilities between species. Despite its ubiquity and its contribution to genome evolution, we currently know little about the dynamics of satellite DNA evolution. The Responder (Rsp) satellite DNA family is found in the pericentric heterochromatin of chromosome 2 of Drosophila melanogaster. Rsp is well-known for being the target of Segregation Distorter (SD)- an autosomal meiotic drive system in D. melanogaster. I present an evolutionary genetic analysis of the Rsp family of repeats in D. melanogaster and its closely-related species in the melanogaster group (D. simulans, D. sechellia, D. mauritiana, D. erecta, and D. yakuba) using a combination of available BAC sequences, whole genome shotgun Sanger reads, Illumina short read deep sequencing, and fluorescence in situ hybridization. I show that Rsp repeats have euchromatic locations throughout the D. melanogaster genome, that Rsp arrays show evidence for concerted evolution, and that Rsp repeats exist outside of D. melanogaster, in the melanogaster group. The repeats in these species are considerably diverged at the sequence level compared to D. melanogaster, and have a strikingly different genomic distribution, even between closely-related sister taxa. The genomic organization of the Rsp repeat in the D. melanogaster genome is complex-it exists of large blocks of tandem repeats in the heterochromatin and small blocks of tandem repeats in the euchromatin. My discovery of heterochromatic Rsp-like sequences outside of D. melanogaster suggests that SD evolved after its target satellite and that the evolution of the Rsp satellite family is highly dynamic over a short evolutionary time scale (<240,000 years).

  16. Dynamics of tandemly repeated DNA sequences during evolution of diploid and tetraploid botiid loaches (Teleostei: Cobitoidea: Botiidae)

    PubMed Central

    Bohlen, Jörg; Šlechtová, Vendula; Altmanová, Marie; Pelikánová, Šárka; Ráb, Petr

    2018-01-01

    Polyploidization has played an important role in the evolution of vertebrates, particularly at the base of Teleostei–an enormously successful ray-finned fish group with additional genome doublings on lower taxonomic levels. The investigation of post-polyploid genome dynamics might provide important clues about the evolution and ecology of respective species and can help to decipher the role of polyploidy per se on speciation. Few studies have attempted to investigate the dynamics of repetitive DNA sequences in the post-polyploid genome using molecular cytogenetic tools in fishes, though recent efforts demonstrated their usefulness. The demonstrably monophyletic freshwater loach family Botiidae, branching to evolutionary diploid and tetraploid lineages separated >25 Mya, offers a suited model group for comparing the long-term repetitive DNA evolution. For this, we integrated phylogenetic analyses with cytogenetical survey involving Giemsa- and Chromomycin A3 (CMA3)/DAPI stainings and fluorescence in situ hybridization with 5S/45S rDNA, U2 snDNA and telomeric probes in representative sample of 12 botiid species. The karyotypes of all diploids were composed of 2n = 50 chromosomes, while majority of tetraploids had 2n = 4x = 100, with only subtle interspecific karyotype differences. The exceptional karyotype of Botia dario (2n = 4x = 96) suggested centric fusions behind the 2n reduction. Variable patterns of FISH signals revealed cases of intraspecific polymorphisms, rDNA amplification, variable degree of correspondence with CMA3+ sites and almost no phylogenetic signal. In tetraploids, either additivity or loci gain/loss was recorded. Despite absence of classical interstitial telomeric sites, large blocks of interspersed rDNA/telomeric regions were found in diploids only. We uncovered different molecular drives of studied repetitive DNA classes within botiid genomes as well as the advanced stage of the re-diploidization process in tetraploids. Our results may

  17. Advances in Cryptococcus genomics: insights into the evolution of pathogenesis.

    PubMed

    Cuomo, Christina A; Rhodes, Johanna; Desjardins, Christopher A

    2018-01-01

    Cryptococcus species are the causative agents of cryptococcal meningitis, a significant source of mortality in immunocompromised individuals. Initial work on the molecular epidemiology of this fungal pathogen utilized genotyping approaches to describe the genetic diversity and biogeography of two species, Cryptococcus neoformans and Cryptococcus gattii. Whole genome sequencing of representatives of both species resulted in reference assemblies enabling a wide array of downstream studies and genomic resources. With the increasing availability of whole genome sequencing, both species have now had hundreds of individual isolates sequenced, providing fine-scale insight into the evolution and diversification of Cryptococcus and allowing for the first genome-wide association studies to identify genetic variants associated with human virulence. Sequencing has also begun to examine the microevolution of isolates during prolonged infection and to identify variants specific to outbreak lineages, highlighting the potential role of hyper-mutation in evolving within short time scales. We can anticipate that further advances in sequencing technology and sequencing microbial genomes at scale, including metagenomics approaches, will continue to refine our view of how the evolution of Cryptococcus drives its success as a pathogen.

  18. Image encryption using random sequence generated from generalized information domain

    NASA Astrophysics Data System (ADS)

    Xia-Yan, Zhang; Guo-Ji, Zhang; Xuan, Li; Ya-Zhou, Ren; Jie-Hua, Wu

    2016-05-01

    A novel image encryption method based on the random sequence generated from the generalized information domain and permutation-diffusion architecture is proposed. The random sequence is generated by reconstruction from the generalized information file and discrete trajectory extraction from the data stream. The trajectory address sequence is used to generate a P-box to shuffle the plain image while random sequences are treated as keystreams. A new factor called drift factor is employed to accelerate and enhance the performance of the random sequence generator. An initial value is introduced to make the encryption method an approximately one-time pad. Experimental results show that the random sequences pass the NIST statistical test with a high ratio and extensive analysis demonstrates that the new encryption scheme has superior security.

  19. MMS Multipoint Analysis of the Dynamics, Evolution, and Particle Acceleration Mechanisms Inside FTEs at Earth's Subsolar Magnetopause

    NASA Astrophysics Data System (ADS)

    Akhavan-Tafti, M.; Slavin, J. A.; Eastwood, J. P.; Cassak, P.; Gershman, D. J.; Zhao, C.

    2017-12-01

    Flux Transfer Events (FTEs) are transient signatures of magnetic reconnection at the dayside magnetopause and play significant roles in determining the rate of reconnection and accelerating particles. This study investigates the magnetohydrodynamic forces inside and outside FTEs to infer the process through which these structures become force-free and uses electron dynamics to study the mechanisms for particle acceleration within the FTE. Akhavan-Tafti et al. [2017] demonstrated that ion-scale FTEs contain regions of elevated plasma density which greatly contribute to plasma pressure forces inside FTEs. It is shown that as FTEs evolve, the plasma is evacuated as the core magnetic field strengthens, hence becoming more force-free. The neighboring ion-scale FTEs formed at the subsolar magnetopause due to multiple X-line reconnection are forced to interact, and likely coalesce. Entropy is invoked to motivate the discussion on the essential role of coalescence in reconfiguring magnetic fields and current density distributions inside FTEs to allow for the adiabatic growth of these structures. Here, we present observational evidence which shows that, in the absence of coalescence, FTEs can become less force free. Local electron kinematics is studied to compare the contributions of parallel electric field, Fermi acceleration, and betatron acceleration mechanisms to particle heating. Acceleration due to parallel electric fields are shown to be dominant in the vicinity of the reconnection site while betatron acceleration controls perpendicular heating inside the FTE in the presence of magnetic pressure gradients. In the downstream of the reconnection site, the `freshly' reconnected field lines start to straighten due to the magnetic curvature force. Straightening field lines accelerate trapped electrons parallel to the local magnetic field (i.e., first-order Fermi acceleration). These acceleration mechanisms are shown to explain the observed anisotropic pitch angle

  20. Phylogeny and character evolution of the coprinoid mushroom genus Parasola as inferred from LSU and ITS nrDNA sequence data.

    PubMed

    Nagy, L G; Kocsubé, S; Papp, T; Vágvölgyi, C

    2009-06-01

    Phylogenetic relationships, species concepts and morphological evolution of the coprinoid mushroom genus Parasola were studied. A combined dataset of nuclear ribosomal ITS and LSU sequences was used to infer phylogenetic relationships of Parasola species and several outgroup taxa. Clades recovered in the phylogenetic analyses corresponded well to morphologically discernable species, although in the case of P. leiocephala, P. lilatincta and P. plicatilis amended concepts proved necessary. Parasola galericuliformis and P. hemerobia are shown to be synonymous with P. leiocephala and P. plicatilis, respectively. By mapping morphological characters on the phylogeny, it is shown that the emergence of deliquescent Parasola taxa was accompanied by the development of pleurocystidia, brachybasidia and a plicate pileus. Spore shape and the position of the germ pore on the spores showed definite evolutionary trends within the group: from ellipsoid the former becomes more voluminous and heart-shaped, the latter evolves from central to eccentric in taxa referred to as 'crown' Parasola species. The results are discussed and compared to other Coprinus s.l. and Psathyrella taxa. Homoplasy and phylogenetic significance of various morphological characters, as well as indels in ITS and LSU sequences, are also evaluated.