Evolution of host-microbe cell adherence by receptor domain shuffling

Abstract

Stable adherence to epithelial surfaces is required for colonization by diverse host-associated microbes. Successful attachment of pathogenic microbes to host cells via adhesin molecules is also the first step in many devastating infections. Despite the primacy of epithelial adherence in establishing host-microbe associations, the evolutionary processes that shape this crucial interface remain enigmatic. Carcinoembryonic antigen associated cell adhesion molecules (CEACAMs) encompass a multifunctional family of vertebrate cell surface proteins which are recurrent targets of bacterial adhesins at epithelial barriers. Here we show that multiple members of the primate CEACAM family exhibit evidence of repeated natural selection at protein surfaces targeted by bacteria, consistent with pathogen-driven evolution. Divergence of CEACAM proteins between even closely related great apes is sufficient to control molecular interactions with a range of bacterial adhesins. Phylogenetic analyses further reveal that repeated gene conversion of CEACAM extracellular domains during primate divergence plays a key role in limiting bacterial adhesin host tropism. Moreover, we demonstrate that gene conversion has continued to shape CEACAM diversity within human populations, with abundant human CEACAM1 variants mediating evasion of adhesins from pathogenic Neisseria. Together this work reveals a mechanism by which gene conversion shapes first contact between microbes and animal hosts.

Host-derived CEACAM-laden vesicles engage enterotoxigenicE. colifor elimination and toxin neutralization

“…On the one hand, a diverse group of pathogens have evolved a variety of adhesins to engage these molecules as receptors. In contrast, under selective pressure of these pathogens, the host may deploy divergent or variant CEACAMs 43 to minimize adhesin engagement and mitigate host tropism, or to target pathogens for destruction [43][44][45][46] .…”

Interactions of pathogenic Escherichia coli with CEACAMs

“…CEACAMs are among the most rapidly evolving proteins in humans. As the extracellular regions of these proteins serve as receptors for a number of important human pathogens, they appear to be under considerable adaptive pressure ( 5 – 7 ) driving CEACAM polymorphisms as well as species-specific diversity ( 5 ). Pathogenic E. coli are among the pathogens known to target CEACAM domains exposed on mucosal surfaces.…”

Specialization restricts the evolutionary paths available to yeast sugar transporters

“…Many key evolutionary innovations arise from changes to protein sequences that alter their function (Cheng 1998;Zhang et al 2002;Clark et al 2003;Dorus et al 2004;Lunzer et al 2005;Nielsen et al 2005;Hoekstra et al 2006;Christin et al 2007;Yokoyama et al 2008;Voordeckers et al 2012;Projecto-Garcia et al 2013;Kaltenbach et al 2018;Jabłońska and Tawfik 2022). Occasionally, these changes stem from dramatic mutational events, including the creation of highly novel coding sequences by gene conversion or ectopic recombination resulting in chimeric proteins (Long and Langley 1993;Nurminsky et al 1998;Wang et al 2000;Long et al 2003;Patthy 2003;Zhang et al 2004;Ciccarelli et al 2005;Arguello et al 2006;Rogers et al 2010;Rogers and Hartl 2012;Leffler et al 2017;Méheust et al 2018;Baker and Hittinger 2019;Smithers et al 2019;Baker et al 2022). While gene conversion can theoretically accelerate the rate of evolution (or even enable adaptation altogether) by bypassing deleterious intermediates, this effect is primarily attributable to the presence of a rugged fitness landscape (Kauffman and Levin 1987;HANSEN et al 2000;Cui et al 2002;Bittihn and Tsimring 2017).…”