Inactivation of the CMAH gene and deficiency of Neu5Gc play a role in human brain evolution

During human evolution, some genes were lost or silenced from the genome of hominins. These missing genes might be the key to the evolution of humans' unique cognitive skills. An inactivation mutation in CMP-N-acetylneuraminic acid hydroxylase (CMAH) was the result of natural selection. The inactivation of CMAH protected our ancestors from some pathogens and reduced the level of N-glycolylneuraminic acid (Neu5Gc) in brain tissue. Interestingly, the low level of Neu5Gc promoted the development of brain tissue, which may have played a role in human evolution. As a xenoantigen, Neu5Gc may have been involved in brain evolution by affecting neural conduction, neuronal development, and aging.