Endocytic CEACAM receptor loss and lack of positive selection in CEACAM1 of birds and snakes indicate absence of pathogen-CEACAM1 interactions in some reptiles

Abstract The CEACAM gene family is among the fastest evolving in vertebrates. It likely originated from an ancestral CEACAM1 -like gene encoding an inhibitory receptor. In mammals, CEACAM1 is expressed on epithelial cells and can regulate leukocyte activation. Thus, several bacterial pathogens exploit it for host entry and immune suppression. Probably this threat selected for the evolution of decoy receptors with CEACAM1-like pathogen-binding domains. In humans, the granulocyte-specific decoy receptor CEACAM3 can redirect CEACAM1-binding pathogens to neutrophils, promoting their uptake and destruction via its endocytic motif. Whether this evolutionary pattern occurs across all vertebrate clades remains unclear. Here, we identified CEACAM families in more than 100 reptile and 244 bird species. Non-avian reptiles such as turtles and crocodiles possessed expanded CEACAM gene families. Alongside the conserved CEACAM19 , found in nearly all mammals, all non-avian reptiles carried CEACAM1 and variable numbers of CEACAM1 -related genes, mostly encoding transmembrane CEACAMs with endocytic ITAM motifs. Notably, snakes lacked these members. In contrast, some bird clades contained only a single CEACAM gene ( CEACAM1 ), while others lacked CEACAM genes entirely. The absence of both decoy receptors and positive selection of CEACAM1 in birds and snakes suggests these clades may lack CEACAM1-binding pathogens.