The distribution of fitness effects of new deleterious amino acid mutations in humans

Eyre-Walker, Adam, Woolfit, Megan and Phelps, Ted (2006) The distribution of fitness effects of new deleterious amino acid mutations in humans. Genetics, 173 2: 891-900. doi:10.1534/genetics.106.057570

Author Eyre-Walker, Adam
Woolfit, Megan
Phelps, Ted
Title The distribution of fitness effects of new deleterious amino acid mutations in humans
Journal name Genetics   Check publisher's open access policy
ISSN 0016-6731
Publication date 2006-06
Sub-type Article (original research)
DOI 10.1534/genetics.106.057570
Volume 173
Issue 2
Start page 891
End page 900
Total pages 10
Place of publication Bethesda, MD, United States
Publisher Genetics Society of America.
Language eng
Subject 060409 Molecular Evolution
0604 Genetics
Formatted abstract
The distribution of fitness effects of new mutations is a fundamental parameter in genetics. Here we present a new method by which the distribution can be estimated. The method is fairly robust to changes in population size and admixture, and it can be corrected for any residual effects if a model of the demography is available. We apply the method to extensively sampled single-nucleotide polymorphism data from humans and estimate the distribution of fitness effects for amino acid changing mutations. We show that a gamma distribution with a shape parameter of 0.23 provides a good fit to the data and we estimate that >50% of mutations are likely to have mild effects, such that they reduce fitness by between one one-thousandth and one-tenth. We also infer that <15% of new mutations are likely to have strongly deleterious effects. We estimate that on average a nonsynonymous mutation reduces fitness by a few percent and that the average strength of selection acting against a nonsynonymous polymorphism is ~9 × 10-5. We argue that the relaxation of natural selection due to modern medicine and reduced variance in family size is not likely to lead to a rapid decline in genetic quality, but that it will be very difficult to locate most of the genes involved in complex genetic diseases.
Keyword Mutation
Population genetics
Genetic disorders
Evolutionary biology
Amino acids
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
School of Biological Sciences Publications
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Created: Fri, 19 Dec 2008, 16:03:09 EST by Diana Guillemin on behalf of School of Biological Sciences