SIGLEC14 (sialic acid binding Ig-like lectin 14)

Siglec-14 is a sialic acid-recognizing activatory receptor found on certain immune cells types that is undergoing concerted evolution with the gene for Siglec-5 (an inhibitory receptor) via ongoing gene conversion of exons encoding amino-terminal V-set lg-like domains. The result is that the two molecules have similar binding properties for sialic acids. However surprisingly, a critical arginine residue required for sialic acid recognition has been mutated in the corresponding molecules from the chimpanzee, gorilla and orangutan. It appears that this may be the ancestral condition, and that the human molecules have restored the arginine residue required for sialic acid recognition. It is unclear what the evolutionary significance of this adjustment is, and further studies are needed. An unusual fusion event between SIGLEC14 and SIGLEC14 results in an allele that is functionally SIGLEC5, but under the control of the SIGLEC14 promoter.  This allele is unique to humans and polymorphic in all human populations studied to date.  Possible selection pressures include the interaction with sialic acid-expressing pathogens and general control of innate immune responses.