Molecular evolution of WDR62, a gene that regulates neocorticogenesis.

Human brain evolution is characterized by dramatic expansion in cerebral cortex size. WDR62 (WD repeat domain 62) is one of the important gene in controlling human cortical development. Mutations in WDR62 lead to primary microcephaly, a neurodevelopmental disease characterized by three to four fold reduction in cerebral cortex size of affected individuals. This study analyzes comparative protein evolutionary rate to provide a useful insight into the molecular evolution of WDR62 and hence pinpointed human specific amino acid replacements. Comparative analysis of human WDR62 with two archaic humans (Neanderthals and Denisovans) and modern human populations revealed that five hominin specific amino acid residues (human specific amino acids shared with two archaic humans) might have been accumulated in the common ancestor of extinct archaic humans and modern humans about 550,000-765,000 years ago. Collectively, the data demonstrates an acceleration of WDR62 sequence evolution in hominin lineage and suggests that the ability of WDR62 protein to mediate the neurogenesis has been altered in the course of hominin evolution.