Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 104, Issue 10, Pages 3907-3912Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0605565104
Keywords
amino acid substitution; deleterious mutation; positive selection; selective constraint
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Funding
- NIGMS NIH HHS [GM 076036, R01 GM076036] Funding Source: Medline
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The selective forces acting on amino acid substitutions may be different in the two phases of molecular evolution: polymorphism and fixation. Negative selection and genetic drift may dominate the first phase, whereas positive selection may become much more significant in the second phase. However, the conventional dichotomy of synonymous vs. nonsynonymous changes does not off er the resolution needed to study the dynamics of these two phases. Following previously published methods, we separated amino acid changes into 75 elementary types (1-bp substitution between their respective codons). The likelihood of each type of amino acid change becoming polymorphic (PI, which stands for polymorphic index), relative to synonymous changes, can then be calculated. Similarly, the likelihood of fixation (FI, for fixation index), conditional on common polymorphisms, is also calculated. Using Perlegen and HapMap data on human polymorphisms and the chimpanzee sequences as the outgroup, we compared the evolutionary dynamics of the 75 elementary changes in the two phases. We found a strong L-shaped negative correlation (P < 0.001) between FI and PI. Only those changes with low Pls show FI > 1, which is often a signature of adaptive evolution. These patterns suggest that negative and positive selection operate more effectively on the same set of amino acid changes and that approximate to 10-13% of amino acid substitutions between humans and chimpanzee may be adaptive.
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