Evolution of CEACAM1 N Domain Biologically Active Sites in Primates.

CEACAMs are involved in a variety of physiological processes including cell adhesion, regulating the immune system, serving as entry receptors for a variety of pathogens, and regulating insulin receptor levels. Earlier studies identified five peptides from the N domain of human CEACAM1 that have stimulatory activity on human neutrophils. We compared the CEACAM N domain sequences, and also the amino acid sequences of the five CEACAM1 N domain peptides with biological activity in human neutrophils, among selected primates. Close similarity of the N domains was observed in the primates examined. The CEACAM1 N domains were more similar within great apes, Old World monkeys, New World monkeys, and lemurs/tarsiers than between groups. Differences in the amino acid sequences of some active peptides were observed among species; some differences are predicted to result in a loss of activity in the human neutrophil system. One amino acid change in the CD66a-1 peptide region that results in the loss of neutrophil activating activity in humans was observed in bonobos but not in the closely related chimpanzee which inhabits the opposite side of the Congo river. The same amino acid change was found to be a very rare event in humans. Changes in the CD66a-2 and CD66a-3 peptide regions were also observed in select human populations, some of which were differentially present in the chimpanzee and bonobo, as well as others that were not found in the other primates studied. In addition, a haplotype involving SNPs resulting in amino acid changes immediately adjacent to peptides CD66a-1, 3, and 7 were found in select human populations. Since CEACAM1 serves as a receptor for multiple infectious agents, selective pressure of an unidentified pathogen could be responsible for these differences. Given the diverse activities of CEACAM1 in humans, variant alleles in these domains might also have diverse effects in different populations.