title: Parallel evolution of a self-signal: humans and new world monkeys independently lost the cell surface sugar Neu5Gc.
abstract: Human sialic acid biology is unusual and thought to be unique among mammals. Humans lack a functional cytidine monophosphate-N-acetylneuraminic acid hydroxylase (CMAH) protein and cannot synthesize the sugar Neu5Gc, an innate mammalian signal of self. Losing this sugar changed how humans interact with some of our deadliest pathogens: malaria, influenza, and streptococcus among others. We show that the New World monkeys, comprising the third of all primate species, have human-like sialic acid biology. They have lost Neu5Gc because of an independent CMAH inactivation ~30 million years ago (mya) (compared to ~3 mya in hominids). This parallel loss of Neu5Gc opens sialic acid biology to comparative phylogenetic analysis and reveals an unexpected conservation priority. New World monkeys risk infection by human pathogens that can recognize cells in the absence of Neu5Gc. This striking molecular convergence provides a mechanism that could explain the long-standing observation that New World monkeys are susceptible to some human diseases that cannot be transmitted to other primates.
authors.affiliation: Glycobiology Research and Training Center, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA, USA.
authors.forename: Stevan A
authors.initials: SA
authors.lastname: Springer
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Diaz
authors.forename: Pascal
authors.initials: P
authors.lastname: Gagneux
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000235:genetics*; D005075:Biological Evolution; D002241:Carbohydrates / Q000235:genetics*; D002462:Cell Membrane / Q000235:genetics*; D006801:Humans; D006899:Mixed Function Oxygenases / Q000235:genetics; D008969:Molecular Sequence Data; D019158:N-Acetylneuraminic Acid / Q000235:genetics; D010802:Phylogeny; D051078:Platyrrhini / Q000235:genetics*; D017386:Sequence Homology, Amino Acid
chemical_list: D000954:Antigens, Surface; D002241:Carbohydrates; D006899:Mixed Function Oxygenases; C074383:CMPacetylneuraminate monooxygenase; D019158:N-Acetylneuraminic Acid