Absence of Neu5Gc and Presence of Anti-Neu5Gc Antibodies in Humans —An Evolutionary Perspective
Conclusions and Perspectives It is interesting that watershed events, such as the loss of Neu5Gc from the glycocalyx of human cells have occurred numerous times in many mammalian and other vertebrate species. These cases of convergent evolution represent precious opportunities for increased understanding of evolutionary processes. In some respects, Neu5Gc is an ideal self-molecule as it is “private” to vertebrates and, based on current data, has yet to be successfully mimicked by microbes. Against the background of this benefit, the loss of Neu5Gc appears paradoxical and may implicate strong selective regimes, either catastrophically caused by pathogens, or under directional sexual selection via female immunity to paternal xenoglycans. Massive genetic drift, or combinations of milder selection and founder events, can also not be excluded. More information on species expected to encounter Neu5Gc in their diets, i.e., mustelids, pinnipeds, and humans, is needed to begin answering several outstanding questions in the field: For instance, what are the potential protective functions of anti-Neu5Gc antibodies in species that lack this sialic acid, especially as regards ongoing protection from cross-species infections by enveloped viruses bearing Neu5Gc on their viral envelopes? Or on the flip-side, what are the potential liabilities of anti-Neu5Gc antibodies due to autoimmunity against incorporated dietary Neu5Gc? Evolutionary events such as the ones discussed here ex...
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