Rapid evolution by positive Darwinian selection in the extracellular domain of the abundant lymphocyte protein CD45...

CD45, encoded by PTPRC in humans, is the most abundantly expressed protein on the surface of many lymphocytes. We investigated whether the extracellular region of CD45 was under positive selection in Old World primates, and whether there was differential selection across this region, particularly on exons that were involved in alternative splicing and those that were not alternatively spliced. The results show extraordinarily strong and consistent positive Darwinian selection on the extracellular part of CD45 throughout the evolution of Old World monkeys, apes and humans. Positive selection is concentrated in exons 9 and 14, which code for the previously neglected linker and fibronectin III domains. These exons have a high rate of evolution at nonsynonymous sites that is roughly twice as high as that of the intronic rate in this gene. In contrast, alternatively spliced exons 4-6, which code for the variable domains, are under weaker positive selection and are evolving more slowly than the intronic rate. These data provide a striking example of positive selection in a well-known gene that should provide an impetus for further functional studies to elucidate its species-specific function.