Format

Send to

Choose Destination
Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):E8155-E8164. doi: 10.1073/pnas.1706306114. Epub 2017 Sep 11.

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

Author information

1
Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093.
2
Center for Academic Research and Training in Anthropogeny, University of California, San Diego, La Jolla, CA 92093.
3
Department of Pathology, University of California, San Diego, La Jolla, CA 92093.
4
Turkana Basin Institute, 00502 Nairobi, Kenya.
5
Department of Anthropology, Stony Brook University, Stony Brook, NY 11794.
6
Glycobiology Research and Training Center, University of California, San Diego, La Jolla, CA 92093; a1varki@ucsd.edu.

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 "ancient glycans" approach to dating of Neu5Gc loss during the evolution of Homo.

KEYWORDS:

evolution; glycobiology; sialic acid

PMID:
28893995
PMCID:
PMC5625913
DOI:
10.1073/pnas.1706306114
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for HighWire Icon for PubMed Central
Loading ...
Support Center