Journal ArticleDOI
Hearing silence: non-neutral evolution at synonymous sites in mammals
TLDR
New evidence indicates that even some synonymous mutations are subject to constraint, often because they affect splicing and/or mRNA stability, which has implications for understanding disease, optimizing transgene design, detecting positive selection and estimating the mutation rate.Abstract:
Although the assumption of the neutral theory of molecular evolution - that some classes of mutation have too small an effect on fitness to be affected by natural selection - seems intuitively reasonable, over the past few decades the theory has been in retreat. At least in species with large populations, even synonymous mutations in exons are not neutral. By contrast, in mammals, neutrality of these mutations is still commonly assumed. However, new evidence indicates that even some synonymous mutations are subject to constraint, often because they affect splicing and/or mRNA stability. This has implications for understanding disease, optimizing transgene design, detecting positive selection and estimating the mutation rate.read more
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PatentDOI
Genomic landscapes of human breast and colorectal cancers
Laura D. Wood,Williams D. Parsons,Sian Jones,Jimmy Lin,Tobias Sjöblom,Thomas D. Barber,Giovanni Parmigiani,Victor E. Velculescu,Kenneth W. Kinzler,Bert Vogelstein +9 more
TL;DR: Based on analysis of exons representing 20,857 transcripts from 18,191 genes, the authors concluded that the genomic landscapes of breast and colorectal cancers are composed of a handful of commonly mutated gene "mountains" and a much larger number of gene "hills" that are mutated at low frequency.
Journal ArticleDOI
Synonymous but not the same: the causes and consequences of codon bias.
Joshua B. Plotkin,Grzegorz Kudla +1 more
TL;DR: Ongoing work to quantify the dynamics of initiation and elongation is as important for understanding natural synonymous variation as it is for designing transgenes in applied contexts.
Journal ArticleDOI
The rise of regulatory RNA.
Kevin V. Morris,John S. Mattick +1 more
TL;DR: A central role for RNA in human evolution and ontogeny is suggested and the emergence of the previously unsuspected world of regulatory RNA from a historical perspective is reviewed.
Journal ArticleDOI
Mistranslation-Induced Protein Misfolding as a Dominant Constraint on Coding-Sequence Evolution
D. Allan Drummond,Claus O. Wilke +1 more
TL;DR: In this article, the authors demonstrate conserved patterns of simple covariation between sequence evolution, codon usage, and mRNA level in E. coli, yeast, worm, fly, mouse, and human that suggest that all observed trends stem largely from a unified underlying selective pressure.
Journal ArticleDOI
Understanding the contribution of synonymous mutations to human disease.
TL;DR: Current understanding of the extent to which synonymous mutations influence disease, the various molecular mechanisms that underlie these effects and the implications for future research and biomedical applications are reviewed.
References
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TL;DR: The results of an international collaboration to produce and make freely available a draft sequence of the human genome are reported and an initial analysis is presented, describing some of the insights that can be gleaned from the sequence.
Journal ArticleDOI
Evolutionary Rate at the Molecular Level
TL;DR: Calculating the rate of evolution in terms of nucleotide substitutions seems to give a value so high that many of the mutations involved must be neutral ones.
Book
The Genetic Basis of Evolutionary Change
TL;DR: A new book that many people really want to read will you be one of them? Of course, you should be as discussed by the authors, even some people think that reading is a hard to do, you must be sure that you can do it.
Journal ArticleDOI
Initial sequence of the chimpanzee genome and comparison with the human genome
Tarjei S. Mikkelsen,LaDeana W. Hillier,Evan E. Eichler,Michael C. Zody,David B. Jaffe,Shiaw-Pyng Yang,Wolfgang Enard,Ines Hellmann,Kerstin Lindblad-Toh,Tasha K. Altheide,Nicoletta Archidiacono,Peer Bork,Jonathan Butler,Jean L. Chang,Ze Cheng,Asif T. Chinwalla,Pieter J. de Jong,Kimberley D. Delehaunty,Catrina Fronick,Lucinda L. Fulton,Yoav Gilad,Gustavo Glusman,Sante Gnerre,Tina Graves,Toshiyuki Hayakawa,Karen E. Hayden,Xiaoqiu Huang,Hongkai Ji,W. James Kent,Mary Claire King,Edward J. Kulbokasl,Ming K. Lee,Ge Liu,Carlos López-Otín,Kateryna D. Makova,Orna Man,Elaine R. Mardis,Evan Mauceli,Tracie L. Miner,William E. Nash,Joanne O. Nelson,Svante Pääbo,Nick Patterson,Craig Pohl,Katherine S. Pollard,Kay Prüfer,Xose S. Puente,David Reich,Mariano Rocchi,Kate R. Rosenbloom,Maryellen Ruvolo,Daniel J. Richter,Stephen F. Schaffner,Arian F.A. Smit,Scott M. Smith,Mikita Suyama,James E. Taylor,David Torrents,Eray Tüzün,Ajit Varki,Gloria Velasco,Mario Ventura,John W. Wallis,Michael C. Wendl,Richard K. Wilson,Eric S. Lander,Robert H. Waterston +66 more
TL;DR: It is found that the patterns of evolution in human and chimpanzee protein-coding genes are highly correlated and dominated by the fixation of neutral and slightly deleterious alleles.
Journal ArticleDOI
Listening to silence and understanding nonsense: exonic mutations that affect splicing
TL;DR: As the splicing mechanisms that depend on exonic signals are elucidated, new therapeutic approaches to treating certain genetic diseases can begin to be explored.
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