title: Multiple changes in sialic acid biology during human evolution.
abstract: Humans are genetically very similar to "great apes", (chimpanzees, bonobos, gorillas and orangutans), our closest evolutionary relatives. We have discovered multiple genetic and biochemical differences between humans and these other hominids, in relation to sialic acids and in Siglecs (Sia-recognizing Ig superfamily lectins). An inactivating mutation in the CMAH gene eliminated human expression of N-glycolylneuraminic acid (Neu5Gc) a major sialic acid in "great apes". Additional human-specific changes have been found, affecting at least 10 of the <60 genes known to be involved in the biology of sialic acids. There are potential implications for unique features of humans, as well as for human susceptibility or resistance to disease. Additionally, metabolic incorporation of Neu5Gc from animal-derived materials occurs into biotherapeutic molecules and cellular preparations--and into human tissues from dietary sources, particularly red meat and milk products. As humans also have varying and sometime high levels of circulating anti-Neu5Gc antibodies, there are implications for biotechnology products, and for some human diseases associated with chronic inflammation.
authors.affiliation: Center for Academic Research and Training in Anthropogeny, Department of Medicine, University of California, San Diego, 9500 Gilman Dr MC 0687, La Jolla, CA 92093-0687, USA. a1varki@ucsd.edu
authors.forename: Ajit
authors.initials: A
authors.lastname: Varki
mesh_terms: D000818:Animals; D005075:Biological Evolution; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D019158:N-Acetylneuraminic Acid / Q000378:metabolism*; D009438:Neuraminic Acids / Q000378:metabolism; D011971:Receptors, Immunologic / Q000378:metabolism; D063267:Sialic Acid Binding Ig-like Lectin 1; D013045:Species Specificity
chemical_list: D008562:Membrane Glycoproteins; D009438:Neuraminic Acids; D011971:Receptors, Immunologic; C571166:SIGLEC1 protein, human; D063267:Sialic Acid Binding Ig-like Lectin 1; C032592:N-glycolylneuraminic acid; D019158:N-Acetylneuraminic Acid
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