Nothing in the Biology of Glycans Makes Sense, Except in the Light of Evolution

All cells in nature display cell surface glycans that are involved in host biological processes, and provide pathogen binding sites. Thus, glycans are trapped in evolutionary “Red Queen” effects, with long‐lived hosts evading their more rapidly evolving pathogens by changing glycan expression, without compromising intrinsic function. This helps explain glycan structural variations in nature, which contributes to biological diversity. Sometimes, one glycan type is eliminated in an evolutionary lineage, e.g., human‐specific loss of the sialic acid Neu5Gc, which affects pathogen recognition. Many human pathogens also disguise themselves with human‐like sialic acids (molecular mimicry) by convergent evolution, thus co‐opting host Siglecs normally dedicated to recognizing self. Such differences between humans and great apes involving sialic acids have implications for unusual features of human immunity. Also, incorporation of Neu5Gc into humans occurs from food, and a similar process contaminates biotherapeutic molecules and cells. As all humans have complement‐fixing anti‐Neu5Gc antibodies, this may contribute to some diseases, and reactions to biotherapeutic products. Finally, we hypothesize that such antibodies restrict transmission of enveloped viruses, and could change fertility, allowing sympatric speciation (collaboration with Pascal Gagneux).