N-glycolyl groups of nonhuman chondroitin sulfates survive in ancient fossils

We identified a glycan modification called N-glycolylated chondroitin sulfate (Gc-CS), derived from metabolic turnover of the nonhuman sialic acid N-glycolylneuraminic acid (Neu5Gc). The presence of Gc-CS could be demonstrated in species rich in Neu5Gc using chemically synthesized Gc-CS as a standard for mass spectrometry. Although humans cannot synthesize Neu5Gc due to a loss-of-function mutation, trace amounts of Gc-CS were found in humans, apparently derived from Neu5Gc-containing foods. Gc-CS was more easily detectable in animal fossils as old as 4 My, allowing indirect fossil evidence of Neu5Gc expression. These findings enable future studies to date the loss of Neu5Gc biosynthesis during human evolution and investigate this glycosaminoglycan modification in humans who consume Neu5Gc-rich foods (red meats).