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1. Unified modeling of gene duplication, loss, and coalescence using a locus tree

Author

Manolis Kellis, Matthew D. Rasmussen, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, and Rasmussen, Matthew D.

Subjects
Gene Transfer, Horizontal, Population, Method, Population genetics, Locus (genetics), Biology, Genome, Coalescent theory, Evolution, Molecular, Species Specificity, Phylogenetics, Gene Duplication, Yeasts, Gene duplication, Genetics, Animals, Humans, education, Phylogeny, Genetics (clinical), education.field_of_study, Models, Statistical, Models, Genetic, Phylogenetic tree, Genetic Loci, Evolutionary biology, Mutation, Algorithms, Gene Deletion
Abstract

Gene phylogenies provide a rich source of information about the way evolution shapes genomes, populations, and phenotypes. In addition to substitutions, evolutionary events such as gene duplication and loss (as well as horizontal transfer) play a major role in gene evolution, and many phylogenetic models have been developed in order to reconstruct and study these events. However, these models typically make the simplifying assumption that population-related effects such as incomplete lineage sorting (ILS) are negligible. While this assumption may have been reasonable in some settings, it has become increasingly problematic as increased genome sequencing has led to denser phylogenies, where effects such as ILS are more prominent. To address this challenge, we present a new probabilistic model, DLCoal, that defines gene duplication and loss in a population setting, such that coalescence and ILS can be directly addressed. Interestingly, this model implies that in addition to the usual gene tree and species tree, there exists a third tree, the locus tree, which will likely have many applications. Using this model, we develop the first general reconciliation method that accurately infers gene duplications and losses in the presence of ILS, and we show its improved inference of orthologs, paralogs, duplications, and losses for a variety of clades, including flies, fungi, and primates. Also, our simulations show that gene duplications increase the frequency of ILS, further illustrating the importance of a joint model. Going forward, we believe that this unified model can offer insights to questions in both phylogenetics and population genetics., National Science Foundation (U.S.) (Career award NSF 0644282)

Published
2012
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2. A high-resolution map of human evolutionary constraint using 29 mammals

Author

Kerstin, Lindblad-Toh, Manuel, Garber, Or, Zuk, Michael F, Lin, Brian J, Parker, Stefan, Washietl, Pouya, Kheradpour, Jason, Ernst, Gregory, Jordan, Evan, Mauceli, Lucas D, Ward, Craig B, Lowe, Alisha K, Holloway, Michele, Clamp, Sante, Gnerre, Jessica, Alföldi, Kathryn, Beal, Jean, Chang, Hiram, Clawson, James, Cuff, Federica, Di Palma, Stephen, Fitzgerald, Paul, Flicek, Mitchell, Guttman, Melissa J, Hubisz, David B, Jaffe, Irwin, Jungreis, W James, Kent, Dennis, Kostka, Marcia, Lara, Andre L, Martins, Tim, Massingham, Ida, Moltke, Brian J, Raney, Matthew D, Rasmussen, Jim, Robinson, Alexander, Stark, Albert J, Vilella, Jiayu, Wen, Xiaohui, Xie, Michael C, Zody, Jen, Baldwin, Toby, Bloom, Chee Whye, Chin, Dave, Heiman, Robert, Nicol, Chad, Nusbaum, Sarah, Young, Jane, Wilkinson, Kim C, Worley, Christie L, Kovar, Donna M, Muzny, Richard A, Gibbs, Andrew, Cree, Huyen H, Dihn, Gerald, Fowler, Shalili, Jhangiani, Vandita, Joshi, Sandra, Lee, Lora R, Lewis, Lynne V, Nazareth, Geoffrey, Okwuonu, Jireh, Santibanez, Wesley C, Warren, Elaine R, Mardis, George M, Weinstock, Richard K, Wilson, Kim, Delehaunty, David, Dooling, Catrina, Fronik, Lucinda, Fulton, Bob, Fulton, Tina, Graves, Patrick, Minx, Erica, Sodergren, Ewan, Birney, Elliott H, Margulies, Javier, Herrero, Eric D, Green, David, Haussler, Adam, Siepel, Nick, Goldman, Katherine S, Pollard, Jakob S, Pedersen, Eric S, Lander, Manolis, Kellis, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, Mag Washietl, Stefan, Kheradpour, Pouya, Ernst, Jason, Ward, Lucas D., Jungreis, Irwin, and Rasmussen, Matthew D.

Subjects
Genome evolution, Genomics, Computational biology, Biology, Human accelerated regions, Genome, Article, Evolution, Molecular, 03 medical and health sciences, 0302 clinical medicine, Animals, Humans, Coding region, Disease, Selection, Genetic, Gene, Phylogeny, 030304 developmental biology, Mammals, Genetics, 0303 health sciences, Multidisciplinary, Genome, Human, Molecular Sequence Annotation, Exons, Sequence Analysis, DNA, 3. Good health, Health, RNA, Human genome, Mobile genetic elements, Sequence Alignment, 030217 neurology & neurosurgery
Abstract

The comparison of related genomes has emerged as a powerful lens for genome interpretation. Here we report the sequencing and comparative analysis of 29 eutherian genomes. We confirm that at least 5.5% of the human genome has undergone purifying selection, and locate constrained elements covering ~4.2% of the genome. We use evolutionary signatures and comparisons with experimental data sets to suggest candidate functions for ~60% of constrained bases. These elements reveal a small number of new coding exons, candidate stop codon readthrough events and over 10,000 regions of overlapping synonymous constraint within protein-coding exons. We find 220 candidate RNA structural families, and nearly a million elements overlapping potential promoter, enhancer and insulator regions. We report specific amino acid residues that have undergone positive selection, 280,000 non-coding elements exapted from mobile elements and more than 1,000 primate- and human-accelerated elements. Overlap with disease-associated variants indicates that our findings will be relevant for studies of human biology, health and disease., National Human Genome Research Institute (U.S.), National Institute of General Medical Sciences (U.S.) (Grant number GM82901), National Science Foundation (U.S.). Postdoctural Fellowship (Award 0905968), National Science Foundation (U.S.). Career (0644282), National Institutes of Health (U.S.) (R01-HG004037), Alfred P. Sloan Foundation., Austrian Science Fund. Erwin Schrodinger Fellowship

Published
2011
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3. A Bayesian Approach for Fast and Accurate Gene Tree Reconstruction

Author

Matthew D. Rasmussen, Manolis Kellis, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Kellis, Manolis, and Rasmussen, Matthew D.

Subjects
0106 biological sciences, Genes, Fungal, Bayesian probability, Genes, Insect, Context (language use), Computational biology, Biology, species tree, Bayesian, 010603 evolutionary biology, 01 natural sciences, Genome, Evolution, Molecular, 03 medical and health sciences, Bayes' theorem, Phylogenetics, Gene Duplication, Gene duplication, Genetics, Animals, Humans, Clade, Molecular Biology, Research Articles, Phylogeny, Ecology, Evolution, Behavior and Systematics, 030304 developmental biology, 0303 health sciences, Models, Genetic, gene duplication and loss, Computational Biology, Bayes Theorem, phylogenetics, Tree (data structure), gene tree, reconciliation, Algorithms
Abstract

Supplementary tables S1, sections 2.1–2.3, and figures S1–S11 are available at Molecular Biology and Evolution online (http://www.mbe.oxfordjournals.org/)., Recent sequencing and computing advances have enabled phylogenetic analyses to expand to both entire genomes and large clades, thus requiring more efficient and accurate methods designed specifically for the phylogenomic context. Here, we present SPIMAP, an efficient Bayesian method for reconstructing gene trees in the presence of a known species tree. We observe many improvements in reconstruction accuracy, achieved by modeling multiple aspects of evolution, including gene duplication and loss (DL) rates, speciation times, and correlated substitution rate variation across both species and loci. We have implemented and applied this method on two clades of fully sequenced species, 12 Drosophila and 16 fungal genomes as well as simulated phylogenies and find dramatic improvements in reconstruction accuracy as compared with the most popular existing methods, including those that take the species tree into account. We find that reconstruction inaccuracies of traditional phylogenetic methods overestimate the number of DL events by as much as 2–3-fold, whereas our method achieves significantly higher accuracy. We feel that the results and methods presented here will have many important implications for future investigations of gene evolution., National Science Foundation (U.S.) (CAREER award NSF 0644282)

Published
2010
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4. Evolution of pathogenicity and sexual reproduction in eight Candida genomes

Author

Marek S. Skrzypek, Piet W. J. de Groot, Mary E. Logue, Steven Bates, David Harris, Neil A. R. Gow, Christina A. Cuomo, Joseph Heitman, Michael A. Quail, Lois L. Hoyer, Michael P. H. Stumpf, Manfred Grabherr, Matthew Berriman, Gavin Sherlock, Bernhard Hube, Esther Rheinbay, Bruce W. Birren, Kevin A. T. Silverstein, Michael C. Lorenz, David R. Soll, Alistair J. P. Brown, Michael F. Lin, Sascha Brunke, Jennifer L. Reedy, Maria C. Santos, Geraldine Butler, Anja Forche, Aaron M. Neiman, Sharadha Sakthikumar, Janet Quinn, Ronny Martin, Manuel A. S. Santos, Carol A. Munro, Martha B. Arnaud, Rodney Staggs, Thyagarajan Srikantha, Florian F. Schmitzberger, Frans M. Klis, Peter E. Sudbery, Elissavet Nikolaou, Chinnappa D. Kodira, Maria C. Costanzo, Manolis Kellis, Judith Berman, Nicola Lennard, Ian Stansfield, David A. Fitzpatrick, Prachi Shah, Qiandong Zeng, Matthew D. Rasmussen, Ino Agrafioti, Molecular Biology and Microbial Food Safety (SILS, FNWI), and Mass Spectrometry of Biomacromolecules (SILS, FNWI)

Subjects
Conserved sequence, Origin and function of meiosis, Mating type, Genes, Fungal, Locus (genetics), Biology, Genome, Article, Evolution, Molecular, 03 medical and health sciences, Saccharomyces, Candida albicans, Codon, Gene, Conserved Sequence, 030304 developmental biology, Genomic organization, Candida, Genetics, 0303 health sciences, Multidisciplinary, Polymorphism, Genetic, Virulence, 030306 microbiology, Reproduction, biology.organism_classification, Diploidy, Sexual reproduction, Meiosis, Genome, Fungal
Abstract

Candida species are the most common cause of opportunistic fungal infection worldwide. Here we report the genome sequences of six Candida species and compare these and related pathogens and non-pathogens. There are significant expansions of cell wall, secreted and transporter gene families in pathogenic species, suggesting adaptations associated with virulence. Large genomic tracts are homozygous in three diploid species, possibly resulting from recent recombination events. Surprisingly, key components of the mating and meiosis pathways are missing from several species. These include major differences at the mating-type loci (MTL); Lodderomyces elongisporus lacks MTL, and components of the a1/2 cell identity determinant were lost in other species, raising questions about how mating and cell types are controlled. Analysis of the CUG leucine-to-serine genetic-code change reveals that 99% of ancestral CUG codons were erased and new ones arose elsewhere. Lastly, we revise the Candida albicans gene catalogue, identifying many new genes. published

Published
2009

5. Accurate gene-tree reconstruction by learning gene- and species-specific substitution rates across multiple complete genomes

Author

Manolis Kellis and Matthew D. Rasmussen

Subjects
Genes, Fungal, Genes, Insect, Genomics, Context (language use), Computational biology, Biology, Synteny, Genome, Heterotachy, Evolution, Molecular, Species Specificity, Artificial Intelligence, Phylogenetics, Genetics, Animals, Phylogeny, Genetics (clinical), Comparative genomics, Models, Genetic, Phylogenetic tree, Phylogenetic network, 12 Drosophila Genomes/Methods, Drosophila, Sequence Alignment
Abstract

Comparative genomics provides a general methodology for discovering functional DNA elements and understanding their evolution. The availability of many related genomes enables more powerful analyses, but requires rigorous phylogenetic methods to resolve orthologous genes and regions. Here, we use 12 recently sequenced Drosophila genomes and nine fungal genomes to address the problem of accurate gene-tree reconstruction across many complete genomes. We show that existing phylogenetic methods that treat each gene tree in isolation show large-scale inaccuracies, largely due to insufficient phylogenetic information in individual genes. However, we find that gene trees exhibit common properties that can be exploited for evolutionary studies and accurate phylogenetic reconstruction. Evolutionary rates can be decoupled into gene-specific and species-specific components, which can be learned across complete genomes. We develop a phylogenetic reconstruction methodology that exploits these properties and achieves significantly higher accuracy, addressing the species-level heterotachy and enabling studies of gene evolution in the context of species evolution.

Published
2007
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6. A comparative encyclopedia of DNA elements in the mouse genome

Author

Ting Wang, Matthew D. Rasmussen, Dana N. Levasseur, Thomas A. Reh, Fidencio Neri, Tanya Kutyavin, Peter J. Good, Katrina Learned, Kate R. Rosenbloom, Lei Hoon See, Cedric Notredame, Ross C. Hardison, Chris Zaleski, Gerd A. Blobel, Dmitri D. Pervouchine, Shane Neph, Ali Mortazavi, Tamer Kahveci, Arthur I. Skoultchi, Peter J. Sabo, Jorg Drenkow, Alex Reynolds, Rebecca F. Lowdon, Marella F. T. R. de Bruijn, John A. Stamatoyannopoulos, Yin Shen, Richard Humbert, Anthony Kirilusha, Sherman M. Weissman, Roderic Guigó, James Taylor, Paul Flicek, Kristen Lee, Shinny Vong, Xiaoyi Cao, Douglas Dunn, Alessandra Breschi, Elise A. Feingold, Michael A. Beer, Piper M. Treuting, Igor Antoshechkin, Thomas R. Gingeras, Georgi K. Marinov, Tyrone Ryba, Jin Lian, Christine M. Disteche, Javier Herrero, Eric Rynes, Sheng Zhong, Weisheng Wu, Richard Sandstrom, Gilberto DeSalvo, Michael Snyder, Meagan Fastuca, Miguel Pignatelli, Mark Groudine, Sarah Djebali, Nergiz Dogan, Rajinder Kaul, Giovanni Bussotti, Henry Amrhein, Daniel Bates, Matthew S. Wilken, Alexander Dobin, Manolis Kellis, Licia Selleri, Diane Trout, Morgan Diegel, David M. Gilbert, Zhihai Ma, Jeff Vierstra, Xiao Qiao Zhou, Theresa K. Canfield, Venkat S. Malladi, Zhen Ye, Anthony Shafer, Tejaswini Mishra, Yiing Lin, Samantha Kuan, Anshul Kundaje, Thalia Papayannopoulou, Pablo Prieto, Robert E. Thurman, Long Pham, Cricket A. Sloan, Olgert Denas, Kathryn Beal, Erika Giste, Andrea Tanzer, Katherine I. Fisher-Aylor, Shin Lin, M. A. Bender, Stuart H. Orkin, Carrie A. Davis, Benjamin D. Pope, Rachel Byron, Srikanta Gosh, Beatriz Lacerda de Sousa, R. Scott Hansen, Brian A. Williams, Yong Cheng, Kanwei Li, Dongwon Lee, Yanli Wang, Evan E. Eichler, Camden Jansen, Feng Yue, Deepti Jain, Miaohua Zhang, David McCleary, W. James Kent, Melissa S. Cline, Kai Hsin Chang, Leslie B. Adams, Robert S. Harris, Ghia Euskirchen, Christapher S. Morrissey, Alexander Y. Rudensky, Philip Cayting, Drew T. Erickson, Eric Haugen, Michael J. Pazin, Vanessa M. Kirkup, Yi-Chieh Wu, Trupti Kawli, Mukul S. Bansal, Cheryl A. Keller, Lee Edsall, Robert M. Samstein, Bing Ren, Miguel Santos, Steven Z. Josefowicz, Barbara J. Wold, Julien Lagarde, Alan P. Boyle, Mitchell J. Weiss, Audra K. Johnson, Massachusetts Institute of Technology. Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science, Wu, Yi-Chieh, Rasmussen, Matthew D., Bansal, Mukul S., and Kellis, Manolis

Subjects
Epigenomics, DNA Replication, Biology, Regulatory Sequences, Nucleic Acid, ENCODE, Genome, Article, Mice, Species Specificity, Animals, Deoxyribonuclease I, Humans, Cell Lineage, Gene Regulatory Networks, Scaffold/matrix attachment region, Gene, ChIA-PET, Conserved Sequence, Genetics, Multidisciplinary, Mouse genome, Molecular Sequence Annotation, Genomics, Chromatin, Gene Expression Regulation, RNA, Human genome, Transcriptome, Genome-Wide Association Study, Transcription Factors
Abstract

The laboratory mouse shares the majority of its protein-coding genes with humans, making it the premier model organism in biomedical research, yet the two mammals differ in significant ways. To gain greater insights into both shared and species-specific transcriptional and cellular regulatory programs in the mouse, the Mouse ENCODE Consortium has mapped transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications and replication domains throughout the mouse genome in diverse cell and tissue types. By comparing with the human genome, we not only confirm substantial conservation in the newly annotated potential functional sequences, but also find a large degree of divergence of sequences involved in transcriptional regulation, chromatin state and higher order chromatin organization. Our results illuminate the wide range of evolutionary forces acting on genes and their regulatory regions, and provide a general resource for research into mammalian biology and mechanisms of human diseases. This work is funded by grants R01HG003991 (B.R.), 1U54HG007004 (T.R.G.), 3RC2HG005602 (M.P.S.), GM083337 and GM085354 (D.M.G.), F31CA165863 (B.D.P.), RC2HG005573 and R01DK065806 (R.C.H.) from the National Institutes of Health, and BIO2011-26205 from the Spanish Plan Nacional and ERC 294653 (to R.G.). J.V. is supported by a National Science Foundation Graduate Research Fellowship under grant no. DGE-071824. K.B., M.P., J.H. and P.F. acknowledge the Wellcome Trust (grant number 095908), the NHGRI (grant number U01HG004695) and the European Molecular Biology Laboratory. We thank G. Hon for helping the analysis of high-throughput enhancer validation. L.S. is supported by R01HD043997-09. S.L. was supported by grants F32HL110473 and K99HL119617.

Published
2014

7. Performance and Scalability of Discriminative Metrics for Comparative Gene Identification in 12 Drosophila Genomes

Author

Matthew D. Rasmussen, Ameya N. Deoras, Manolis Kellis, and Michael F. Lin

Subjects
Molecular Sequence Data, Genomics, Sequence alignment, Computational biology, Computational Biology/Comparative Sequence Analysis, Biology, Genome, Sensitivity and Specificity, Cellular and Molecular Neuroscience, Open Reading Frames, Discriminative model, Species Specificity, Genetics, Animals, Drosophila Proteins, lcsh:QH301-705.5, Molecular Biology, Ecology, Evolution, Behavior and Systematics, Comparative genomics, Ecology, Base Sequence, Chromosome Mapping, Discriminant Analysis, Genetic Variation, Reproducibility of Results, Genome project, Sequence Analysis, DNA, Linear discriminant analysis, Computational Biology/Evolutionary Modeling, lcsh:Biology (General), Computational Theory and Mathematics, Modeling and Simulation, Pairwise comparison, Drosophila, Research Article, Computational Biology/Genomics
Abstract

Comparative genomics of multiple related species is a powerful methodology for the discovery of functional genomic elements, and its power should increase with the number of species compared. Here, we use 12 Drosophila genomes to study the power of comparative genomics metrics to distinguish between protein-coding and non-coding regions. First, we study the relative power of different comparative metrics and their relationship to single-species metrics. We find that even relatively simple multi-species metrics robustly outperform advanced single-species metrics, especially for shorter exons (≤240 nt), which are common in animal genomes. Moreover, the two capture largely independent features of protein-coding genes, with different sensitivity/specificity trade-offs, such that their combinations lead to even greater discriminatory power. In addition, we study how discovery power scales with the number and phylogenetic distance of the genomes compared. We find that species at a broad range of distances are comparably effective informants for pairwise comparative gene identification, but that these are surpassed by multi-species comparisons at similar evolutionary divergence. In particular, while pairwise discovery power plateaued at larger distances and never outperformed the most advanced single-species metrics, multi-species comparisons continued to benefit even from the most distant species with no apparent saturation. Last, we find that genes in functional categories typically considered fast-evolving can nonetheless be recovered at very high rates using comparative methods. Our results have implications for comparative genomics analyses in any species, including the human., Author Summary Comparing the genomes of related species is a powerful approach to the discovery of functional elements such as protein-coding genes. Theoretically, using more species should lead to more discovery power. Many questions remain, however, surrounding the optimal choice of species to compare and how to best use multi-species alignments. It is even possible that practical limitations in the sequencing, assembly, and alignment of genomes could effectively negate the benefit of using more species. Here, we used 12 complete fly genomes to study a variety of metrics used to identify protein-coding genes, including methods that analyze only the genome of interest and comparative methods that examine evolutionary signatures in genome alignments. We found that species over a surprisingly broad range of phylogenetic distances were effective in comparative analyses, and that discovery power continued to scale with each additional species without apparent saturation. We also examined whether comparative methods systematically miss genes considered fast-evolving, and studied how performance is influenced by genome alignment strategies. Our results can help guide species selection for future comparative studies and provide methodological guidance for a variety of gene identification tasks, including the design of future de novo gene predictors and the search for unusual gene structures.

Published
2008

8. Evolution of genes and genomes on the Drosophila phylogeny

Author

Adam M. Phillippy, Edward Grandbois, Pen MacDonald, Iain MacCallum, Laura K. Reed, Wojciech Makalowski, Tracey Honan, Tania Tassinari Rieger, Melissa J. Hubisz, Josep M. Comeron, Douglas Smith, Jennifer Godfrey, Sebastian Strempel, Amr Abdouelleil, Brenton Gravely, Harindra Arachi, Albert J. Vilella, Marc Azer, Sarah A. Teichmann, Roger A. Hoskins, Corbin D. Jones, Keenan Ross, Derek Wilson, Stuart J. Newfeld, John Stalker, Thomas D. Watts, Dennis C. Friedrich, Therese A. Markow, Michael U. Mollenhauer, Tina Goode, Geneva Young, Terry Shea, Krista Lance, Karin A. Remington, Kevin A. Edwards, Lynne Aftuck, Cecil Rise, Sheridon Channer, Matthew D. Rasmussen, Nicole Stange-Thomann, Annie Lui, Robert A. Reenan, Todd Sparrow, Dave Begun, Tamrat Negash, Laura K. Sirot, Adrianne Brand, Adam Brown, Daisuke Yamamoto, Pema Phunkhang, Justin Abreu, Russell Schwartz, Ana Llopart, Abderrahim Farina, Kebede Maru, Chung-I Wu, Allen Alexander, Scott Anderson, So Jeong Lee, Jason Blye, Gary H. Karpen, Wilfried Haerty, Daniel A. Barbash, Peter Rogov, Barry O'Neill, Rachel Mittelman, Jakob Skou Pedersen, Leanne Hughes, Robert K. Bradley, Graziano Pesole, Wyatt W. Anderson, Anthony J. Greenberg, Alejandro Sánchez-Gracia, Julio Rozas, Stephen W. Schaeffer, Yama Thoulutsang, Roger K. Butlin, David H. Ardell, Stuart DeGray, Chris P. Ponting, Deborah E. Stage, Corrado Caggese, Montserrat Aguadé, Casey M. Bergman, Diallo Ferguson, Peili Zhang, Jeffrey R. Powell, Hajime Sato, Xiaohong Liu, Marta Sabariego Puig, Michael Parisi, Passang Dorje, Yoshihiko Tomimura, Adal Abebe, Carlo G. Artieri, Brian Hurhula, Filip Rege, Peter D. Keightley, Andrew Barry, Pablo Alvarez, Tsamla Tsamla, Marvin Wasserman, Santosh Jagadeeshan, Daniel L. Halligan, Chelsea D. Foley, Kim D. Delehaunty, Manfred Grabherr, Sourav Chatterji, Angela N. Brooks, James C. Costello, Mieke Citroen, James A. Yorke, Hsiao Pei Yang, Charles Chapple, Jian Lu, Carlos A. Machado, Norbu Dhargay, Tsering Wangchuk, Anat Caspi, Patrick Cahill, Tashi Bayul, Lisa Levesque, Otero L. Oyono, Atanas Mihalev, Dawa Thoulutsang, Dawn N. Abt, Sujaa Raghuraman, Manyuan Long, Maria Mendez-Lago, Charles Matthews, Kimberly Dooley, Alex Wong, Melanie A. Huntley, William R. Jeck, Ira Topping, Ben Kanga, José P. Abad, Ana Cristina Lauer Garcia, Brikti Abera, Kunsang Gyaltsen, Jonathan Butler, Alicia Franke, Michael C. Schatz, Cheewhye Chin, Charles F. Aquadro, Justin Johnson, Bryant F. McAllister, Georgia Giannoukos, M. Erii Husby, Rod A. Wing, Shangtao Liu, Jean L. Chang, Jennifer Daub, Eiko Kataoka, Leopold Parts, Rakela Lubonja, Margaret Priest, Yoshiko N. Tobari, Teena Mehta, Evgeny M. Zdobnov, Yeshi Lokyitsang, Richard Elong, Matthew J. Parisi, Louis Meneus, Eric S. Lander, Alan Filipski, Gary Gearin, Nabil Hafez, Nicholas Sisneros, David B. Jaffe, Ian Holmes, Marina Sirota, Leonid Boguslavskiy, Lisa Chuda, LaDeana W. Hillier, Meizhong Luo, Phil Batterham, Michael Kleber, Richard K. Wilson, Yama Cheshatsang, Qing Yu, Rebecca Reyes, Matthew W. Hahn, Andreas Heger, Mar Marzo, Patrick Minx, Kerstin Lindblad-Toh, Vera L. S. Valente, Adam Wilson, William C. Jordan, Mohamed A. F. Noor, Chiao-Feng Lin, Asha Kamat, Heather Ebling, Mihai Pop, Frances Letendre, Mariana F. Wolfner, Don Gilbert, Ngawang Sherpa, Riza M. Daza, Oana Mihai, Gabriel C. Wu, Aaron M. Berlin, Ewen F. Kirkness, Monika D. Huard, Robert S. Fulton, Randall H. Brown, Danni Zhong, Sharon Stavropoulos, Venky N. Iyer, Xu Mu, Christina R. Gearin, David M. Rand, Jerry A. Coyne, Dan Hultmark, Jill Falk, Christopher Patti, Montserrat Papaceit, James Meldrim, Valentine Mlenga, Muneo Matsuda, Sven Findeiß, Todd A. Schlenke, Kevin McKernan, Brian P. Walenz, Timothy B. Sackton, Leonardo Koerich, Peter An, Robert Nicol, Chuong B. Do, Dmitry Khazanovich, Carmen Segarra, Maura Costello, St Christophe Acer, Claudia Rohde, Serafim Batzoglou, Hadi Quesneville, Evan Mauceli, Andy Vo, Luciano M. Matzkin, Susan E. Celniker, Patrick M. O’Grady, William M. Gelbart, Lloyd Low, Jamal Abdulkadir, Jessica Spaulding, Brian R. Calvi, Charlotte Henson, Robert David, Jennifer L. Hall, Andrew G. Clark, Anastasia Gardiner, Susan M. Russo, Birhane Hagos, Kerri Topham, Amy Denise Reily, Eli Venter, Jerome Naylor, Sandra W. Clifton, Valer Gotea, Samuel R. Gross, Manolis Kellis, Claude Bonnet, Christopher Strader, Tashi Lokyitsang, Nyima Norbu, Jennifer Baldwin, Stephen M. Mount, Robert L. Strausberg, Shailendra Yadav, Kristipati Ravi Ram, Steven L. Salzberg, Erik Gustafson, David A. Garfield, Eva Freyhult, Arthur L. Delcher, Enrico Blanco, Granger G. Sutton, Jason M. Tsolas, Charles Robin, Angie S. Hinrichs, Christopher D. Smith, Jane Wilkinson, Brendan McKernan, Fritz Pierre, William McCusker, Brian Oliver, Barry E. Garvin, Sudhir Kumar, Peter Kisner, Kunsang Dorjee, A. Bernardo Carvalho, Anna Montmayeur, Andrew Zimmer, Diana Shih, Wei Tao, Shiaw Pyng Yang, Sante Gnerre, Sampath Settipalli, Thu Nguyen, Paolo Barsanti, Brian P. Lazzaro, Sonja J. Prohaska, J. Craig Venter, Senait Tesfaye, Susan McDonough, Kim D. Pruitt, Alexander Stark, Sergio Castrezana, Lucinda Fulton, Richard T. Lapoint, Greg Gibson, John Spieth, Boris Adryan, Georgius De Haan, Sheila Fisher, Daniel A. Pollard, Seva Kashin, Rob J. Kulathinal, Michael B. Eisen, Nathaniel Novod, Christina Demaso, Alan Dupes, Amanda M. Larracuente, Toby Bloom, Alfredo Villasante, Charles H. Langley, Rama S. Singh, Niall J. Lennon, Kristi L. Montooth, Daniel Barker, Wolfgang Stephan, David Sturgill, Ruiqiang Li, Andrew Hollinger, Boris Boukhgalter, Talene Thomson, Patrick Cooke, Zac Zwirko, Nadia D. Singh, Michael Weiand, Lior Pachter, Roderic Guigó, Yu Zhang, Jay D. Evans, Stephanie Bosak, Rosie Levine, Lu Shi, Kiyohito Yoshida, Carolyn S. McBride, Pouya Kheradpour, William Brockman, Alberto Civetta, Hiroshi Akashi, Marcia Lara, Susan Faro, Sam Griffiths-Jones, Michael R. Brent, Thomas H. Eickbush, Gane Ka-Shu Wong, Elizabeth P. Ryan, Erica Anderson, Roberta Kwok, Asif T. Chinwalla, Sahal Osman, Nga Nguyen, Damiano Porcelli, Missole Doricent, Saverio Vicario, Marc Rubenfield, Bárbara Negre, Gillian M. Halter, Erin E. Dooley, Elena R. Lozovsky, William Lee, Alville Collymore, Catherine Stone, Tanya Mihova, Jun Wang, Karsten Kristiansen, Imane Bourzgui, Michael F. Lin, Katie D'Aco, Filipe G. Vieira, Choe Norbu, Yu-Hui Rogers, Aaron L. Halpern, Eugene W. Myers, Sharleen Grewal, Robert T. Good, Alfredo Ruiz, Dave Kudrna, Joseph Graham, Alex Lipovsky, Leonidas Mulrain, Tsering Wangdi, Roman Arguello, Mira V. Han, Arjun Bhutkar, Rasmus Nielsen, David J. Saranga, Aleksey V. Zimin, Vasilia Magnisalis, Helen Vassiliev, Thomas C. Kaufman, Eva Markiewicz, Temple F. Smith, Jinlei Liu, Loryn Gadbois, Michael G. Ritchie, Lisa Zembek, Daniel Bessette, Pasang Bachantsang, Adam Navidi, Department of Molecular Biology and Genetics, Cornell University [New York], Lawrence Berkeley National Laboratory [Berkeley] (LBNL), University of California [Berkeley], University of California, Agencourt Bioscience Corporation, Partenaires INRAE, Faculty of Life Science, University of Manchester [Manchester], Laboratory of Cellular and Developmental Biology (LCDB), NIDDK, NIH, Department of Ecology and Evolutionary Biology, University of Arizona, Department of Biology, Indiana University [Bloomington], Indiana University System-Indiana University System, Massachusetts Institute of Technology (MIT), Harvard University [Cambridge], Centro de Biología Molecular Severo Ochoa [Madrid] (CBMSO), Universidad Autonoma de Madrid (UAM)-Consejo Superior de Investigaciones Científicas [Madrid] (CSIC), Brown University, Laboratory of Molecular Biology, Medical Research Council, Departament de Genetica, Universitat de Barcelona (UB), Pennsylvania State University (Penn State), Penn State System-Penn State System, Department of Genetics, University of Georgia [USA], Uppsala University, Department of Ecology and Evolution [Lausanne], Université de Lausanne (UNIL), McMaster University, School of Biology, IE University, Università degli Studi di Bari Aldo Moro, University of Melbourne, Stanford University, University of California [Davis] (UC Davis), Boston University [Boston] (BU), Centro de Regulación Genómica (CRG), Universitat Pompeu Fabra [Barcelona] (UPF), Washington University in Saint Louis (WUSTL), University of Sheffield, Syracuse University, Universidade Federal Rural do Rio de Janeiro (UFRRJ), Department of Bioengineering, Beihang University (BUAA), Tucson Stock Center, Genome Center, University of California-University of California, Genome Sequencing Center, University of Washington School of Medicine, University of Winnipeg, Iowa State University (ISU), Indiana University System, The Wellcome Trust Sanger Institute [Cambridge], Center for Bioinformatics and Computational Biology, University of Delaware [Newark], Illinois State University, University of Rochester [USA], United States Department of Agriculture (USDA), Arizona State University [Tempe] (ASU), Leipzig University, Universidade Federal do Rio Grande do Sul (UFRGS), Duke University, North Carolina State University [Raleigh] (NC State), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of Connecticut (UCONN), Computer Science Département, Université Saint-Esprit de Kaslik (USEK), Mc Master University, Indiana University, Institute of Evolutionary Biology, University of Edinburgh, J. Craig Venter Institute [La Jolla, USA] (JCVI), University of Oxford [Oxford], Center for Biomolecular Science and Engineering, Unité de Recherche Génomique Info (URGI), Institut National de la Recherche Agronomique (INRA), and Zdobnov, Evgeny

Subjects
melanogaster genome, 0106 biological sciences, RNA, Untranslated, [SDV]Life Sciences [q-bio], Genome, Insect, RNA, Untranslated/genetics, Genes, Insect, 01 natural sciences, Genome, Genome, Insect/ genetics, Gene Order, Genome, Mitochondrial/genetics, Drosophila Proteins, Phylogeny, ddc:616, Genetics, 0303 health sciences, Multidisciplinary, biology, Reproduction, Genomics, Multigene Family/genetics, Reproduction/genetics, DNA Transposable Elements/genetics, Genes, Insect/ genetics, Multigene Family, dosage compensation, Drosophila, amino-acid substitution, Drosophila Protein, Drosophila Proteins/genetics, Synteny/genetics, fruit-fly, 010603 evolutionary biology, Synteny, Drosophila sechellia, Evolution, Molecular, 03 medical and health sciences, Phylogenetics, Molecular evolution, Codon/genetics, [SDV.BV]Life Sciences [q-bio]/Vegetal Biology, Animals, adaptive protein evolution, Codon, 030304 developmental biology, Gene Order/genetics, molecular evolution, fungi, Immunity, synonymous codon usage, Sequence Analysis, DNA, Immunity/genetics, biology.organism_classification, Drosophila mojavensis, Evolutionary biology, Genome, Mitochondrial, DNA Transposable Elements, maximum-likelihood, noncoding dna, Drosophila/ classification/ genetics/immunology/metabolism, Sequence Alignment, natural-selection, Drosophila yakuba
Abstract

Affiliations des auteurs : cf page 216 de l'article; International audience; Comparative analysis of multiple genomes in a phylogenetic framework dramatically improves the precision and sensitivity of evolutionary inference, producing more robust results than single-genome analyses can provide. The genomes of 12 Drosophila species, ten of which are presented here for the first time (sechellia, simulans, yakuba, erecta, ananassae, persimilis, willistoni, mojavensis, virilis and grimshawi), illustrate how rates and patterns of sequence divergence across taxa can illuminate evolutionary processes on a genomic scale. These genome sequences augment the formidable genetic tools that have made Drosophila melanogaster a pre-eminent model for animal genetics, and will further catalyse fundamental research on mechanisms of development, cell biology, genetics, disease, neurobiology, behaviour, physiology and evolution. Despite remarkable similarities among these Drosophila species, we identified many putatively non-neutral changes in protein-coding genes, non-coding RNA genes, and cis-regulatory regions. These may prove to underlie differences in the ecology and behaviour of these diverse species.

Published
2007
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9. Discovery of functional elements in 12 Drosophila genomes using evolutionary signatures

Author

Matthew W. Hahn, Angie S. Hinrichs, Benedict Paten, Colin N. Dewey, Stein Aerts, Jacques van Helden, Yongkyu Park, Madeline A. Crosby, Seung-Won Park, J. Graham Ruby, Alexander Stark, Sushmita Roy, Emily Hodges, David P. Bartel, Pouya Kheradpour, Michael B. Eisen, Gregory J. Hannon, Julius Brennecke, Michael P. Weir, Morgan L. Maeder, Lior Pachter, Benjamin J. Polansky, Jakob Skou Pedersen, Eric C. Lai, Bryanne E. Robson, Anat Caspi, Douglas Smith, David Haussler, W. James Kent, Andrew G. Clark, Susan E. Celniker, Deborah Eastman, Michael F. Lin, Mira V. Han, Ameya N. Deoras, Donald G. Gilbert, Thomas C. Kaufman, Joseph W. Carlson, Bassem A. Hassan, Matthew D. Rasmussen, Michael D. Rice, William M. Gelbart, Manolis Kellis, and Leopold Parts

Subjects
Sequence analysis, Genome, Insect, Molecular Sequence Data, Genomics, Genes, Insect, Computational biology, Biology, Genome, Article, Evolution, Molecular, Phylogenetics, Molecular evolution, Untranslated Regions, Animals, Drosophila Proteins, Gene, Conserved Sequence, Phylogeny, Comparative genomics, Genetics, Multidisciplinary, Binding Sites, Base Sequence, Exons, MicroRNAs, Gene Expression Regulation, Organ Specificity, Drosophila, Drosophila Protein
Abstract

Sequencing of multiple related species followed by comparative genomics analysis constitutes a powerful approach for the systematic understanding of any genome. Here, we use the genomes of 12 Drosophila species for the de novo discovery of functional elements in the fly. Each type of functional element shows characteristic patterns of change, or 'evolutionary signatures', dictated by its precise selective constraints. Such signatures enable recognition of new protein-coding genes and exons, spurious and incorrect gene annotations, and numerous unusual gene structures, including abundant stop-codon readthrough. Similarly, we predict non-protein-coding RNA genes and structures, and new microRNA (miRNA) genes. We provide evidence of miRNA processing and functionality from both hairpin arms and both DNA strands. We identify several classes of pre- and post-transcriptional regulatory motifs, and predict individual motif instances with high confidence. We also study how discovery power scales with the divergence and number of species compared, and we provide general guidelines for comparative studies.

Published
2007
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