January 16, 2009

Selection on human mtDNA from ratio of nonsynonymous to synonymous mutations

Molecular Biology and Evolution, doi:10.1093/molbev/msp005

Temporal trails of natural selection in human mitogenomes

Sankar Subramanian


Mildly deleterious mutations initially contribute to the diversity of a population but later they are selected against at high frequency and are eliminated eventually. Using over 1500 complete human mitochondrial genomes along with those of Neanderthal and Chimpanzee, I provide empirical evidence for this prediction by tracing the footprints of natural selection over time. The results show a highly significant inverse relationship between the ratio of nonsynonymous- to synonymous divergence (dN/dS) and the age of human haplogroups. Furthermore this study suggests that slightly deleterious mutations constitute up to 80% of the mitochondrial amino acid replacement mutations detected in human populations and that over the last 500,000 years these mutations have been gradually removed.