Human-specific evolutionary changes in the biology of siglecs.
Siglecs are a family of sialic acid-recognizing immunoglobulin-like lectins that exhibit multiple human-specific and human-universal differences, including changes in binding specificity (Siglec-5, -7, -9, -11, -12 and 14); changes in expression pattern (Siglec-1, -5, -6, and -11); gene conversion (SIGLEC11); gene deletion (SIGLEC13) and pseudogenization (SIGLEC17). Human-unique pseudogenes of SIGLEC12, SIGLEC14 and SIGLEC16 are also polymorphic within human populations, suggesting ongoing selection on this family of genes. The apparently higher concentration of SIGLEC changes in the human lineage may have been selected by interactions with pathogens binding Siglecs, and/or as compensatory responses to the loss of the sialic acid N-glycolylneuraminic acid (Neu5Gc) in humans. Human-specific Siglec changes of particular interest include expression of Siglec-11 in brain microglia, expression of Siglec-6 on placental trophoblast, suppression of Siglec-5 expression on adaptive immune cells, new expression of Siglec-5 on amniotic epithelium, and elimination of Siglec-13 and -17 from innate immune cells. The Siglec-13 and -17 inactivation events fixed in the ancestral population shortly before the common ancestor of modern humans 100–200 thousand years ago, and resurrected Siglec-13 and -17 gene products bind potentially lethal pathogens of infants. While such pathogens may have contributed to population bottlenecks in human evolution, the resulting changes in sialic acid biology may also have altered multiple systems where sialic acid and Siglecs have endogenous roles. Thus, genes associated with sialic acid biology appear to be a “hot spot” of genetic and physiological change during human evolution, with implications for human origins, and for uniquely human features in health and disease.
Adv Exp Med Biol. 2015;842:1-16. doi: 10.1007/978-3-319-11280-0_1.
Departments of Medicine, and Cellular and Molecular Medicine, Glycobiology Research and Training Center, University of California San Diego, La Jolla, CA, USA, fschwarz@ucsd.edu.
