MBE Advance Access published online on December 19, 2007
Molecular Biology and Evolution, doi:10.1093/molbev/msm281
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Research Article |
Mammalian Nonsynonymous Sites are not Overdispersed: Comparative Genomic Analysis of Index of Dispersion of Mammalian Proteins
School of Biology, Georgia Institute of Technology, 310 Ferst Drive, Atlanta, GA 30332, USA
* Corresponding author TEL 404-385-6084, FAX 404-894-2295, email: soojinyi{at}gatech.edu
Received for publication September 5, 2007. Revision received November 28, 2007. Revision received December 12, 2007. Accepted for publication December 13, 2007.
It is often stated that patterns of nonsynonymous rate variation among mammalian lineages are more irregular than expected, or ‘overdispersed’ under the neutral model, whereas synonymous sites conform to the neutral model. Here we re-examined genome-wide patterns of the variance to mean ratio, or index of dispersion (R), of substitutions in proteins from human, mouse and dog. Contrary to the prevailing notion, we found that the mean index of dispersion for nonsynonymous sites of mammalian proteins is not significantly different from 1. We propose that earlier analyses were biased because the data included disproportionately more protein hormones, which tend to be more dispersed than genes in other functional categories. Synonymous sites exhibit greater degree of dispersion than nonsynonymous sites, although similar to earlier estimates and potentially due to errors associated with correction for multiple hits. Overall, our analyses identify strong genome-wide generation time effect and natural selection as important determinants of among-lineage variation of protein evolutionary rates. Furthermore, patterns of lineage specific selective constraint are consistent with the nearly neutral model of molecular evolution.
Key Words: Index of Dispersion • lineage effects • neutral theory • nearly neutral theory • comparative genomics • gene ontology
Current Address: Division of Biostatistics, School of Medicine, Indiana University, 1050 Wishard Boulevard, RG 4101, Indianapolis, IN 46202-2872
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