A second uniquely human mutation affecting sialic acid biology
Siglecs are immunoglobulin superfamily member lectins that selectively recognize different types and linkages of sialic acids, which are major components of cell surface and secreted glycoconjugates. We report here a human Siglec-like molecule (Siglec-L1) that lacks a conserved arginine residue known to be essential for optimal sialic acid recognition by previously known Siglecs. Loss of the arginine from an ancestral molecule was caused by a single nucleotide substitution that occurred after the common ancestor of humans with the great apes but before the origin of modern humans. The chimpanzee Siglec-L1 ortholog remains fully functional and preferentially recognizes N-glycolylneuraminic acid, which is a common sialic acid in great apes and other mammals. Reintroducing the ancestral arginine into the human molecule regenerates the same properties. Thus, the single base pair mutation that replaced the arginine on human Siglec-L1 is likely to be evolutionarily related to the previously reported loss of N-glycolylneuraminic acid expression in the human lineage. Siglec-L1 and its chimpanzee Siglec ortholog also have a different expression pattern from previously reported Siglecs because they are found on the lumenal edge of epithelial cell surfaces. Notably, the human genome contains several Siglec-like pseudogenes that have independent mutations that would have replaced the arginine residue required for optimal sialic acid recognition. Thus, additional changes in the biology of sialic acids may have taken place during human evolution.
J Biol Chem. 2001 Oct 26;276(43):40282-7. Epub 2001 Aug 23
Glycobiology Research and Training Center, Department of Medicine, University of California at San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0687, USA.
