A Potential Molecular Mechanism for the Speciation of Genus Homo

Session Date: 
Feb 5, 2016

The human species underwent a watershed change in the biochemical composition of its cell surfaces, via a genetic event estimated to have occurred ~2-3 million years ago, which is also the apparent period of the emergence of the genus Homo. A loss-of function mutation occurred in CMAH (responsible for transforming the cell surface sialic acid Neu5Ac into its derivative Neu5Gc), a change affecting many millions of molecules per cell, altering diverse biological functions. Analyses of fossil sialic acids confirm that Neanderthals also lacked Neu5Gc. Early Homo became a top predator and increased its exposure to pathogens from a broad prey basis. The initial CMAH mutation would have conveyed a strong survival advantage to homozygous individuals by providing resistance to pathogens using Neu5Gc as a target receptor in other animals. But how did the mutation become fixed, i.e. carried in two copies by every living individual of our ancestral population?  Using mice with a human-like Cmah defect, we have shown that such a mutation can come under strong sexual selection, due to female immunity against sperm carrying the mismatched sialic acid. The radical makeover of cell surfaces in early Homo would thus have brought about a mismatch between females lacking, and males still expressing Neu5Gc, essentially providing a mechanism for reproductive isolation and speciation.  Improved glycan biochemistry of African fossils may eventually help to differentiate contemporaneous lineages of the relevant period into two groups, and the ones deficient in CMAH products are most likely to have contributed to the origins of the genus Homo.

File 2016_02_05_07_Gagneux-Web.mp472.7 MB