141W Poster - Evolutionary Genetics
Wednesday June 08, 9:15 PM - 10:00 PM

Authors:
EmilyClare Baker ¹; Ryan Sayegh ^1,2; Kristin Kohler ¹; Wyatt Borman ¹; Matthew Barber ¹

Affiliations:
1) Institute of Ecology and Evolution, University of Oregon, Eugene, OR; 2) Department of Molecular, Cellular & Developmental Biology, University of Colorado Boulder, Boulder, CO

Keywords:
Other (host-pathogen interactions)

Epithelial cells are often the first point of contact between microbes and their animal hosts. As such, epithelial interactions with pathogenic microbes play a key role in determining successful microbial colonization or clearance. Pathogens may therefore be an important source of selective pressure for proteins on epithelial surfaces. While the pathogen binding surfaces of dedicated immune proteins may have significant evolutionary flexibility, pressure to maintain critical cellular functions could constrain the evolution of other epithelial proteins in response to pathogen antagonism. Despite the importance of epithelial surface proteins in establishing host-microbe associations, how these interactions evolve over time remains largely undefined.

Bacterial adhesins are a diverse class of surface proteins that mediate binding and attachment to host epithelia. A common target of bacterial adhesins are CEACAM proteins, a multifunctional vertebrate family of cell adhesion molecules that play important roles in development and tissue homeostasis. CEACAM proteins are widely expressed across epithelia, with some also expressed on neutrophils. Here we show that a subset of primate CEACAM proteins are evolving rapidly with high levels of divergence in the extracellular N domain. The CEACAM N domain is critical for CEACAM protein function, but it is also the binding site for bacterial adhesins. We observe that diversification of the N domain has been accelerated by recurrent gene conversion among bacterially antagonized CEACAM orthologs. Furthermore, gene conversion events in this domain appear to make up the majority of human polymorphisms for the bacterially targeted CEACAM proteins, CEACAM1, CEACAM3, and CEACAM5 (CEA). Using biochemical protein binding experiments, we show that both between and within species diversity determines recognition by a panel of bacterial adhesins from the human pathogens Helicobacter pylori and Neisseria gonorrhoeae. Collectively our study suggests that gene conversion is an important mechanism by which multifunctional proteins can evolve in response to pathogen antagonism.