FOXP2 (forkhead box P2)

Through genetic analysis of large human family "KE", where many family members experinced language disorder, Lai et al. (2001) mapped gene responsible for language disorder as FOXP2, a fork-head domain including transcription factor protein coding gene.  Because amino acid sequence of human FOXP2 protein is different from its mouse ortholog for only 3 amino acids, this gene has some important function among all mammalian species.  In this sense, FOXP2 is not human specific, while language ability is human specific.  However,  Enerd et al. (2002) and Zhang et al. (2002) found that 2 out of 3 amino acid differences between mouse and human FOXP2 proteins occurred in human lineage, after human-chimpanzee common ancestor.  They also showed that genetic divrersity of this gene is quite low compared to typical human genomic region, suggesting positive selection on this gene in recent times (less than 100,000 years ago).  Zhang et al. (2002) also examined various mammalian species, and found that carnivores also experienced one amino acid substitution identical with human.    More recenly, Krause et al. (2007) found  FOXP2 sequence from Neandertals identical with modern humans.  This suggests that two nonsynonymous mutations causing two amino acid changes predated divergence of modern humans and Neanderthals. 

  FOXP2 human type gene was knocked-in to mice by Fujita et al. (2008), and they found ultrasonic vocalization was imparied in knocked-in mice, as well as abormal Purkinje cells. Enard et al. (2009) also made FOXP2 knock-in mice, and observed some effects to cortico-basal ganglia circuits.  It is still not clear if these two amino acid substitutions in modern human are really responsible for human language acquisition.

 Contributed by Saitou Naruya, domain leader of Genetics section.