Comparative functional analyses of the prostate-specific KLK3 enzyme in primates reveal the impact of sexual selection.

Male reproductive proteins frequently evolve rapidly in animals, potentially due to adaptive evolution driven by sperm competition, polyspermy avoidance, or pathogen defense. Alternatively, elevated rates of protein change may be due to relaxed constraint. The prostate-specific protease KLK3 has experienced dynamic evolution since its origin stemming from a gene duplication in the ancestor of all Old World primates, with instances of rapid evolution, stasis, and pseudogenization. As we demonstrate with functional assays using recombinant proteins, these changes have resulted in a chimpanzee KLK3 ortholog with greater enzyme velocity and higher efficiency than other apes, including humans. Reduced enzyme efficiency was observed in gorillas and gibbons who both possess a chimeric KLK2/KLK3 enzyme resulting from independent genomic deletions. The relative efficiency of KLK3 homologs among these species correlates well with their presumed levels of sperm competition. Furthermore, the reconstructed protein of the human-chimpanzee last common ancestor has enzyme kinetics identical to modern humans, suggesting that the observed functional differences between humans and chimpanzees are derived in the latter and allowing us to tentatively speculate that their common ancestor did not possess a polygynandrous mating system similar to modern chimpanzees.