SIGLEC13 (sialic acid binding Ig-like lectin 13)
The gene for Siglec-13 was specifically deleted in humans by an Alu-mediated recombination event. The protein Siglec-13 is expressed on chimpanzee monocytes, innate immune cells that react to bacteria. Chimpanzee Siglec-13 recruits the DAP12 signaling adapter and bind sialic acids. Expression in innate immune cells alters inflammatory cytokine secretion in response to Toll-like receptor-4 stimulation. The ancestral Siglec-13 is shown to also be engaged by two potentially lethal sialylated bacterial pathogens of newborns and infants, agents with a likely impact on reproductive fitness. Neanderthal and Denisovan genomes show human-like sequences, corroborating estimates that the initial pseudogenization event occurred in the common ancestral population of these species. Sequences flanking the SIGLEC13 deletion in humans also show limited polymorphic diversity, suggesting the there were selection forces closely predating the origin of modern humans. Taken together, the data suggest that genetic elimination of Siglec-13 represents a signature of infectious and/or other inflammatory processes that may have contributed to population restrictions during hominin origins.