Evolution of CEACAM pathogen decoy receptors in primates.

Area of Science:

• Evolutionary biology
• Immunology
• Genomics

Background:

• The CEACAM1 protein on leukocytes regulates immune responses, but pathogens exploit it for host entry.
• Decoy receptors evolved to counteract pathogen binding to CEACAM1.
• Human CEACAM3 acts as an endocytic receptor for CEACAM1-binding pathogens, while CEACAM5 and CEACAM6 roles are less understood.

Purpose of the Study:

• To investigate the evolutionary selection of CEACAMs in primates.
• To determine if CEACAM5 and CEACAM6 function as decoy receptors.

Main Methods:

• Analysis of CEACAM gene selection across 148 primate species.
• Examination of nonsynonymous to synonymous substitution rates (dN/dS) in CEACAM N-domain exons.
• Identification of polymorphisms in human CEACAM5.

Main Results:

• Functional CEACAM3 genes are absent in gibbons and New World monkeys.
• CEACAM6 in these primates shows high dN/dS ratios in pathogen-binding domains, similar to CEACAM1.
• CEACAM5 also exhibits selection for diversification in its pathogen-binding regions across most primates, with specific polymorphisms observed in African populations.

Conclusions:

• CEACAM5 and CEACAM6 are under evolutionary selection to mimic the pathogen receptor CEACAM1.
• These proteins likely function as decoy receptors in most primate species.
• This provides a mechanism to maintain defense against pathogens in the absence of CEACAM3.