The Evolution of Human-Specific Genes by Duplication

Huxley and Darwin were among the first to appreciate the close evolutionary relationship of humans and other African great apes but also to ponder what genetic changes might make us human. Initial comparisons of human and chimpanzee genes, however, showed little difference (>99% identical) despite the numerous adaptations that must have occurred on the human lineage. Recent studies of more complex regions of our genome have revealed hotspots of rapid and dramatic evolutionary change. Embedded within these regions are hundreds of new duplicate genes, several of which appear to be important in unique human-specific neuroanatomical adaptations, including the expansion of the neocortex and increase in synaptic connectivity. Paradoxically, this genetic complexity has led to a high background rate of copy number mutations causing childhood diseases (e.g., autism, intellectual disability, and epilepsy) suggesting that human-specific genes and increased disease burden are tightly linked.