Rates of molecular evolution predict intraspecies genetic diversity

Abstract

Because the evolution of modern humans from early mammals has been a continuous process, human genetic diversity at the molecular level should reflect mammalian genetic diversity. To test this prediction, we contrasted the proportion of segregating sites, q, in human data from the 1000 Genome Project with phylogenetic trees of genes in 96 mammalian genomes ranging from human to platypus. The evolvability of a gene in the human population was found to be positively correlated with the long-term molecular evolutionary rate (r = 0.592). Further analysis of human singleton and de novo mutations suggested that natural selection begins shaping intraspecies genetic diversity soon after a mutation9s initial appearance. By introducing the rate of molecular evolution as a predictor of q, species-specific selection on genes can be detected as deviations from predicted values. We analyzed the average deviations of 10,173 disease-related gene sets and detected 33 gene sets likely to be under human species-specific selection. Among them, nine gene sets were related, with highly significant and positive t-values, to substance-related disorders, thus indicating that the accelerated evolution of the natural reward pathway is the most representative adaptation in humans. Eight gene sets were significantly related, with negative t-values, to infectious diseases. This result may reflect co-evolution between pathogens and humans or recent bottlenecks in the human population caused by pandemic infectious diseases. Our findings demonstrate the potential usefulness of this population genomics approach that incorporates the rates of long-term molecular evolution as predictors.