@article {314879, title = {N-glycolyl groups of nonhuman chondroitin sulfates survive in ancient fossils}, journal = {PNAS}, year = {2017}, month = {09/2017}, abstract = {

Biosynthesis of the common mammalian sialic acid\ N-glycolylneuraminic acid (Neu5Gc) was lost during human evolution due to inactivation of the\ CMAH\ gene, possibly expediting divergence of the\ Homo\ lineage, due to a partial fertility barrier. Neu5Gc catabolism generates\ N-glycolylhexosamines, which are potential precursors for glycoconjugate biosynthesis. We carried out metabolic labeling experiments and studies of mice with human-like Neu5Gc deficiency to show that Neu5Gc degradation is the metabolic source of UDP-GlcNGc and UDP-GalNGc and the latter allows an unexpectedly selective incorporation of\ N-glycolyl groups into chondroitin sulfate (CS) over other potential glycoconjugate products. Partially\ N-glycolylated-CS was chemically synthesized as a standard for mass spectrometry to confirm its natural occurrence. Much lower amounts of GalNGc in human CS can apparently be derived from Neu5Gc-containing foods, a finding confirmed by feeding Neu5Gc-rich chow to human-like Neu5Gc-deficient mice. Unlike the case with Neu5Gc,\ N-glycolyl-CS was also stable enough to be detectable in animal fossils as old as 4 My. This work opens the door for investigating the biological and immunological significance of this glycosaminoglycan modification and for an {\textquotedblleft}ancient glycans{\textquotedblright} approach to dating of Neu5Gc loss during the evolution of\ Homo.

}, doi = {10.1073/pnas.1706306114}, url = {http://www.pnas.org/content/early/2017/09/05/1706306114}, author = {Bergfeld, Anne K. and Lawrence, Roger and Diaz, Sandra L. and Pearce, Oliver M. T. and Ghaderi, Darius and Gagneux, Pascal and Leakey, Meave G. and Ajit Varki} }