Evolution of host-microbe cell adherence by receptor domain shuffling

Abstract
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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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https://www.ncbi.nlm.nih.gov/assembly/GCF_000151905.2/
1. University of Washington
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NCBI, GCA_002880775.3.

https://www.ncbi.nlm.nih.gov/assembly/GCF_002880775.1
1. Vervet Genomics Consortium
(2014) Chlorocebus_sabeus 1.1
NCBI, GCF_000409795.2.

https://www.ncbi.nlm.nih.gov/assembly/GCF_000409795.2
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1. Laboratory for conservation and utilization of Bio-resource
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NCBI, GCF_000364345.1.

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NCBI, GCA_000952055.2 .

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Article and author information

Author details

EmilyClare P Baker

Institute of Ecology and Evolution, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0002-7875-2144
Ryan Sayegh

Institute of Ecology and Evolution, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
Kristin M Kohler

Institute of Ecology and Evolution, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
Wyatt Borman

Institute of Ecology and Evolution, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
Claire K Goodfellow

Institute of Ecology and Evolution, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
Eden R Brush

Institute of Ecology and Evolution, University of Oregon, Eugene, United States

Competing interests
The authors declare that no competing interests exist.
Matthew F Barber

Department of Biology, University of Oregon, Eugene, United States

For correspondence
mfbarber@uoregon.edu

Competing interests
The authors declare that no competing interests exist.

"This ORCID iD identifies the author of this article:" 0000-0003-2008-2165

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

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.