The completion of the human, chimpanzee, and macaque genomes coupled with large-scale experiments to document human genetic variation provide us an unprecedented opportunity to study the evolution of our species. In collaboration with Andy Clark and Rasmus Nielsen, our group has been developing novel tools to facilitate this study as well as applying the tools to novel and interesting data sets. For example, as a joint effort between our three groups, we recently completed the first genome-wide comparison of human genetic variation within protein-coding genes to the genetic differences between humans and chimpanzees. In this experiment, our collaborators at Celera Genomics sequenced 20,362 putative genes in 39 people (19 African- Americans and 20 European-Americans) and a male chimpanzee. Using novel statistical approaches, we identified over 300 genes that show too much amino acid divergence between humans and chimpanzees and thus are likely involved in the adaptive molecular evolution of our species. Interestingly, genes involved in immunity and defense and regulation of transcription (when genes are turned on or off) show particularly high rates of adaptive molecular evolution, consistent with several previous studies.

We also identified more than 800 genes that showed plentiful amino acid variation within humans, but little divergence between humans and chimpanzees. Biological processes enriched for such genes include cytoskeletal formation, general vesicle transport, ectoderm development, alcohol metabolism, and muscle formation. Many amino acid polymorphisms in these genes are presumably mildly harmful since they reach appreciable frequencies only within local human populations and are prevented from becoming fixed between species due to their effects on reproductive fitness.