Jun 3, 2008

Assessing the evolutionary impact of amino acid mutations in the human genome

PLoS Genetics
Adam R BoykoCarlos D Bustamante

Abstract

Quantifying the distribution of fitness effects among newly arising mutations in the human genome is key to resolving important debates in medical and evolutionary genetics. Here, we present a method for inferring this distribution using Single Nucleotide Polymorphism (SNP) data from a population with non-stationary demographic history (such as that of modern humans). Application of our method to 47,576 coding SNPs found by direct resequencing of 11,404 protein coding-genes in 35 individuals (20 European Americans and 15 African Americans) allows us to assess the relative contribution of demographic and selective effects to patterning amino acid variation in the human genome. We find evidence of an ancient population expansion in the sample with African ancestry and a relatively recent bottleneck in the sample with European ancestry. After accounting for these demographic effects, we find strong evidence for great variability in the selective effects of new amino acid replacing mutations. In both populations, the patterns of variation are consistent with a leptokurtic distribution of selection coefficients (e.g., gamma or log-normal) peaked near neutrality. Specifically, we predict 27-29% of amino acid changing (nonsynonymous) ...Continue Reading

  • References48
  • Citations292

References

  • References48
  • Citations292

Citations

Mentioned in this Paper

Computer Software
MBNL1 gene
Patterns
RCHY1 gene
Epoch
European American
Exons
Genome
Likelihood Functions
African Continental Ancestry Group

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