Evolution of host-microbe cell adherence by receptor domain shuffling
- University of Oregon, United States
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.
Data availability
The following files contain the images, data and/or code used to perform analyses and generate figures for this work, Figure 3 - Source data 1, Figure 3 - SuppFig 1 - source data 1, Figure 5 - Source data 1, Figure 6 - Source data 1, Figure 6 - Source data 2, Figure 6 - SuppFig 3 - source data 1, Figure 6 - SuppFig 4 - source data 1.
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Macaca_fascicularis_5.0NCBI, GCF_000364345.1.
Article and author information
Author details
EmilyClare P Baker
Funding
National Institutes of Health (R35GM133652)
- Matthew F Barber
National Institutes of Health (F32AI147565)
- EmilyClare P Baker
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Copyright
© 2022, Baker et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Evolution of host-microbe cell adherence by receptor domain shuffling
eLife 11:e73330.
https://doi.org/10.7554/eLife.73330
Further reading
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