Rates and Genomic Consequences of Spontaneous Mutational Events in Drosophila melanogaster
TLDR
This work sequenced eight genomes produced by a mutation-accumulation experiment in Drosophila melanogaster to estimate genome-wide rates of large deletions and tandem duplications and reveals that point mutation and small indel rates vary significantly between the two different genetic backgrounds examined.Abstract:
Because spontaneous mutation is the source of all genetic diversity, measuring mutation rates can reveal how natural selection drives patterns of variation within and between species. We sequenced eight genomes produced by a mutation-accumulation experiment in Drosophila melanogaster. Our analysis reveals that point mutation and small indel rates vary significantly between the two different genetic backgrounds examined. We also find evidence that ∼2% of mutational events affect multiple closely spaced nucleotides. Unlike previous similar experiments, we were able to estimate genome-wide rates of large deletions and tandem duplications. These results suggest that, at least in inbred lines like those examined here, mutational pressures may result in net growth rather than contraction of the Drosophila genome. By comparing our mutation rate estimates to polymorphism data, we are able to estimate the fraction of new mutations that are eliminated by purifying selection. These results suggest that ∼99% of duplications and deletions are deleterious--making them 10 times more likely to be removed by selection than nonsynonymous mutations. Our results illuminate not only the rates of new small- and large-scale mutations, but also the selective forces that they encounter once they arise.read more
Citations
More filters
Journal Article
Copy number variation in association studies of human disease
TL;DR: In this article, the authors discuss evidence that copy-number variants affect phenotypes, directions for basic knowledge to support clinical study of CNVs, the challenge of genotyping CNPs in clinical cohorts, the use of SNPs as markers for CNPs and statistical challenges in testing CNVs for association with disease.
Journal ArticleDOI
Precise estimates of mutation rate and spectrum in yeast
TL;DR: This work sequencing the genomes of 145 diploid mutation accumulation (MA) lines of the budding yeast Saccharomyces cerevisiae identified nearly 1,000 mutations, a larger number than in any prior eukaryotic MA experiment as far as the authors are aware, and for the first time, in MA data, rates of context-dependent single-nucleotide mutations are estimated.
Journal ArticleDOI
Genetic diversity of the African malaria vector Anopheles gambiae.
Alistair Miles,Alistair Miles,Nicholas J. Harding,Giordano Bottà,Giordano Bottà,Chris S Clarkson,Chris S Clarkson,Tiago Antao,Tiago Antao,Tiago Antao,Krzysztof Kozak,Daniel R. Schrider,Andrew D. Kern,Seth Redmond,Igor V. Sharakhov,Igor V. Sharakhov,Richard D. Pearson,Richard D. Pearson,Christina M. Bergey,Michael C. Fontaine,Martin J. Donnelly,Martin J. Donnelly,Mara K. N. Lawniczak,Diego Ayala,Nora J. Besansky,Austin Burt,Beniamino Caputo,Alessandra della Torre,H. Charles J. Godfray,Matthew W. Hahn,Janet Midega,Daniel E. Neafsey,Samantha M. O’Loughlin,João Pinto,Michelle M. Riehle,Kenneth D. Vernick,David Weetman,Craig S. Wilding,Craig S. Wilding,Bradley J. White,Arlete D. Troco,Abdoulaye Diabaté,Carlo Costantini,Kyanne R. Rohatgi,Nohal Elissa,Boubacar Coulibaly,Joao Dinis,Charles M. Mbogo,Philip Bejon,Henry D. Mawejje,Jim Stalker,Kirk A. Rockett,Eleanor Drury,Daniel Mead,Anna E. Jeffreys,Christina Hubbart,Kate Rowlands,Alison T. Isaacs,Dushyanth Jyothi,Cinzia Malangone,Paul Vauterin,Ben Jeffery,Ian J. Wright,Lee Hart,Krzysztof Kluczynski,Victoria Cornelius,Bronwyn MacInnis,Christa Henrichs,Rachel Giacomantonio,Dominic P. Kwiatkowski,Dominic P. Kwiatkowski +70 more
TL;DR: These data revealed complex population structure and patterns of gene flow, with evidence of ancient expansions, recent bottlenecks, and local variation in effective population size.
Journal ArticleDOI
Estimation of the spontaneous mutation rate per nucleotide site in a Drosophila melanogaster full-sib family
TL;DR: Deep genome sequencing of two parents and 12 of their offspring to estimate the mutation rate per site per generation in a full-sib family of Drosophila melanogaster recently sampled from a natural population suggests an effective population size for the species of ∼1.4 × 106.9 million.
Journal ArticleDOI
Evolution of Resistance Against CRISPR/Cas9 Gene Drive.
TL;DR: It is shown that resistance to standard CGD approaches should evolve almost inevitably in most natural populations, unless repair of CGD-induced cleavage via NHEJ can be effectively suppressed, or resistance costs are on par with those of the driver.
References
More filters
Journal ArticleDOI
The Sequence Alignment/Map format and SAMtools
Heng Li,Bob Handsaker,Alec Wysoker,T. J. Fennell,Jue Ruan,Nils Homer,Gabor T. Marth,Gonçalo R. Abecasis,Richard Durbin +8 more
TL;DR: SAMtools as discussed by the authors implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments.
Journal ArticleDOI
Fast and accurate short read alignment with Burrows–Wheeler transform
Heng Li,Richard Durbin +1 more
TL;DR: Burrows-Wheeler Alignment tool (BWA) is implemented, a new read alignment package that is based on backward search with Burrows–Wheeler Transform (BWT), to efficiently align short sequencing reads against a large reference sequence such as the human genome, allowing mismatches and gaps.
Book ChapterDOI
Primer3 on the WWW for general users and for biologist programmers.
Steve Rozen,Helen Skaletsky +1 more
TL;DR: This chapter assumes acquaintance with the principles and practice of PCR, as outlined in, for example, refs.
Journal ArticleDOI
The genome sequence of Drosophila melanogaster
Mark Raymond Adams,Susan E. Celniker,Robert A. Holt,Cheryl A. Evans,Jeannine D. Gocayne,Peter Amanatides,Steve Scherer,Peter W. Li,Roger A. Hoskins,R. Galle,Reed A. George,Suzanna E. Lewis,Stephen Richards,Michael Ashburner,Scott Henderson,Granger G. Sutton,Jennifer R. Wortman,Mark Yandell,Qing Zhang,Lin Chen,Rhonda C. Brandon,Yu-Hui Rogers,R. Blazej,Mark Champe,Barret D. Pfeiffer,Kenneth H. Wan,Colleen Doyle,E. G. Baxter,Gregg Helt,Catherine R. Nelson,G. L. Gabor Miklos,Josep F. Abril,A. Agbayani,Huijin An,C. Andrews-Pfannkoch,Danita Baldwin,Richard M. Ballew,Anand Basu,James Baxendale,Leyla Bayraktaroglu,Ellen M. Beasley,Karen Beeson,Panayiotis V. Benos,Benjamin P. Berman,D. Bhandari,Slava Bolshakov,Dana Borkova,Michael R. Botchan,John Bouck,Peter Brokstein,Philippe Brottier,Kenneth C. Burtis,Dana A. Busam,Heather Butler,Edouard Cadieu,I. Chandra,J. Michael Cherry,Simon Cawley,Carl Dahlke,Lionel Davenport,P. Davies,B. de Pablos,Arthur L. Delcher,Zuoming Deng,A. Deslattes Mays,Ian M. Dew,Susanne Dietz,Kristina Dodson,Lisa Doup,Michael Downes,Shannon Dugan-Rocha,B. C. Dunkov,Patrick J. Dunn,K. J. Durbin,Carlos Evangelista,Concepcion Ferraz,Steven Ferriera,Wolfgang Fleischmann,Carl Fosler,Andrei Gabrielian,Neha Garg,William M. Gelbart,Kenneth Glasser,A. Glodek,Fangcheng Gong,J. Harley Gorrell,Zhiping Gu,Ping Guan,Michael Harris,Nomi L. Harris,Damon A. Harvey,Thomas J. Heiman,Judith Hernandez,Jarrett Houck,Damon Hostin,K. Houston,Timothy Howland,Ming-Hui Wei,Chinyere Ibegwam,M. Jalali,Francis Kalush,Gary H. Karpen,Zhaoxi Ke,James A. Kennison,K. A. Ketchum,B. E. Kimmel,Chinnappa D. Kodira,Cheryl L. Kraft,Saul A. Kravitz,David Kulp,Zhongwu Lai,Paul Lasko,Yiding Lei,Alexander Levitsky,Jun Li,Zhenya Li,Yunye Liang,Xiaoying Lin,Xiangjun Liu,B. Mattei,Tina C. McIntosh,Michael P. McLeod,D. McPherson,Gennady V. Merkulov,Natalia Milshina,Clark M. Mobarry,J. Morris,A. Moshrefi,Stephen M. Mount,Mee Moy,Brian Murphy,Lee Murphy,Donna M. Muzny,David L. Nelson,David R. Nelson,Keith Nelson,K. Nixon,Deborah R. Nusskern,Joanne Pacleb,Michael J. Palazzolo,G. S. Pittman,Sue Pan,J. Pollard,Vinita Puri,Martin G. Reese,Knut Reinert,Karin A. Remington,Robert D. C. Saunders,Robert D. C. Saunders,F. Scheeler,H. Shen,B. Christopher Shue,Inga Siden-Kiamos,Michael Simpson,Marian P. Skupski,Thomas J. Smith,Eugene G. Spier,Allan C. Spradling,Mark Stapleton,Renee Strong,E. Sun,Robert Svirskas,C. Tector,Russell Turner,Eli Venter,Aihui Wang,Xianyuan Wang,Zhen Yuan Wang,David A. Wassarman,George M. Weinstock,Jean Weissenbach,Sherita Williams,Trevor Woodage,Kim C. Worley,D. Wu,Shih-Hung Yang,Q. Alison Yao,Jane Ye,R. F. Yeh,Jayshree Zaveri,Ming Zhan,Gefei Zhang,Qi Zhao,Liansheng Zheng,Xiangqun Zheng,Fei Zhong,Wenyan Zhong,X. Zhou,Shiaoping C. Zhu,Xiancan Zhu,Hamilton O. Smith,Richard A. Gibbs,Eugene W. Myers,Gerald M. Rubin,J. Craig Venter +194 more
TL;DR: The nucleotide sequence of nearly all of the approximately 120-megabase euchromatic portion of the Drosophila genome is determined using a whole-genome shotgun sequencing strategy supported by extensive clone-based sequence and a high-quality bacterial artificial chromosome physical map.
Journal ArticleDOI
Accurate whole human genome sequencing using reversible terminator chemistry
David R. Bentley,Shankar Balasubramanian,Harold Swerdlow,Harold Swerdlow,Geoffrey Paul Smith,John Milton,John Milton,Clive Gavin Brown,Clive Gavin Brown,Kevin Hall,Dirk J. Evers,Colin Barnes,Colin Barnes,Helen Bignell,Jonathan Mark Boutell,Jason Bryant,Richard J. Carter,R. Keira Cheetham,Anthony J. Cox,Darren James Ellis,Michael R. Flatbush,Niall Anthony Gormley,Sean Humphray,Leslie J. Irving,Mirian S. Karbelashvili,Scott M. Kirk,Heng Li,Xiaohai Liu,Xiaohai Liu,Klaus Maisinger,Lisa Murray,Bojan Obradovic,Tobias William Barr Ost,Michael Lawrence Parkinson,M. R. Pratt,Isabelle Rasolonjatovo,Mark T. Reed,Roberto Rigatti,Chiara Rodighiero,Mark T. Ross,Andrea Sabot,Subramanian V. Sankar,Aylwyn Scally,Gary P. Schroth,Mark Smith,Vincent Peter Smith,Anastassia Spiridou,Peta E. Torrance,Svilen S. Tzonev,Eric Vermaas,Klaudia Walter,Wu Xiaolin,Lu Zhang,Mohammed D. Alam,Carole Anastasi,Ify C. Aniebo,David Mark Dunstan Bailey,Iain R. Bancarz,Saibal Banerjee,Selena G. Barbour,Primo Baybayan,Vincent A. Benoit,Kevin Benson,Claire Bevis,Phillip J. Black,Asha Boodhun,Joe S. Brennan,John Bridgham,Rob C. Brown,Andrew A. Brown,Dale Buermann,Abass A. Bundu,James C. Burrows,Nigel P. Carter,Nestor Castillo,Maria Chiara E. Catenazzi,Simon Chang,R. Neil Cooley,Natasha R. Crake,Olubunmi O. Dada,Konstantinos D. Diakoumakos,Belen Dominguez-Fernandez,David James Earnshaw,David James Earnshaw,Ugonna C. Egbujor,David W. Elmore,Sergey Etchin,Mark R. Ewan,Milan Fedurco,Louise Fraser,Karin Fuentes Fajardo,W. Scott Furey,David George,Kimberley J. Gietzen,Colin P. Goddard,George Stefan Golda,Philip A. Granieri,David E. Green,David L. Gustafson,Nancy F. Hansen,Kevin Harnish,Christian D. Haudenschild,Narinder I. Heyer,Matthew M. Hims,Johnny T. Ho,Adrian Horgan,Katya Hoschler,Steve Hurwitz,Denis V. Ivanov,Maria Q. Johnson,Terena James,T. A. Huw Jones,Gyoung-Dong Kang,Tzvetana H. Kerelska,Alan D. Kersey,Irina Khrebtukova,Alex P. Kindwall,Zoya Kingsbury,Paula Kokko-Gonzales,Anil Kumar,Marc Laurent,Cindy Lawley,Sarah E. Lee,Xavier Lee,Arnold Liao,Jennifer A. Loch,Mitch Lok,Shujun Luo,Radhika M. Mammen,John W. Martin,Patrick Mccauley,Paul McNitt,Parul Mehta,Keith W. Moon,Joe W. Mullens,Taksina Newington,Zemin Ning,Bee Ling Ng,Sonia M. Novo,Michael J. O'Neill,Mark A. Osborne,Mark A. Osborne,Andrew Osnowski,Omead Ostadan,Lambros L. Paraschos,Lea Pickering,Andrew C. Pike,Alger C. Pike,D. Chris Pinkard,Daniel P. Pliskin,Joe Podhasky,Victor J. Quijano,Come Raczy,Vicki H. Rae,Stephen Rawlings,Ana Chiva Rodriguez,Phyllida M. Roe,John Rogers,Maria Candelaria Rogert Bacigalupo,Nikolai Romanov,Anthony Romieu,Rithy K. Roth,Natalie J. Rourke,Silke Ruediger,Eli Rusman,Raquel Maria Sanches-Kuiper,Martin R. Schenker,Josefina M. Seoane,Richard Shaw,Mitch K. Shiver,Steven W. Short,Ning Sizto,Johannes P. Sluis,Melanie Anne Smith,Jean Ernest Sohna Sohna,Eric J. Spence,Kim B. Stevens,Neil Sutton,Lukasz Szajkowski,Carolyn Tregidgo,Gerardo Turcatti,Stephanie Vandevondele,Yuli Verhovsky,Selene M. Virk,Suzanne Wakelin,Gregory C. Walcott,Jingwen Wang,Graham John Worsley,Juying Yan,Ling Yau,Mike Zuerlein,Jane Rogers,James C. Mullikin,Matthew E. Hurles,Nick J. McCooke,Nick J. McCooke,John Stephen West,Frank L. Oaks,Peter Lundberg,David Klenerman,Richard Durbin,Anthony J. Smith +201 more
TL;DR: An approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost is reported, effective for accurate, rapid and economical whole-genome re-sequencing and many other biomedical applications.