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Multiple stages of evolutionary change in anthrax toxin receptor expression in humans

Lauren A. Choate, Gilad Barshad, Pierce W. McMahon, Iskander Said, Edward J. Rice, Paul R. Munn, James J. Lewis, View ORCID ProfileCharles G. Danko
doi: https://doi.org/10.1101/2020.07.29.227660
Lauren A. Choate
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
2Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853
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Gilad Barshad
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Pierce W. McMahon
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Iskander Said
2Department of Molecular Biology and Genetics, Cornell University, Ithaca, NY 14853
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Edward J. Rice
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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Paul R. Munn
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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James J. Lewis
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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  • For correspondence: dankoc@gmail.com jjl336@cornell.edu
Charles G. Danko
1Baker Institute for Animal Health, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
3Department of Biomedical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853
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  • ORCID record for Charles G. Danko
  • For correspondence: dankoc@gmail.com jjl336@cornell.edu
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Abstract

The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease influenced human evolution, we studied changes in human expression of anthrax toxin receptor 2 (ANTXR2), which encodes a cell surface protein necessary for Bacillus anthracis virulence toxins to cause anthrax disease. In immune cells, ANTXR2 was 8-fold down-regulated in all available human samples compared to non-human primates, indicating regulatory changes early in the evolution of modern humans. We also observed multiple genetic signatures consistent with recent positive selection driving a European-specific decrease in ANTXR2 expression in several non-immune tissues affected by anthrax toxins. Our observations fit a model in which humans adapted to anthrax disease following early ecological changes associated with hunting and scavenging, as well as a second period of adaptation after the rise of modern agriculture.

Competing Interest Statement

The authors have declared no competing interest.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted July 30, 2020.
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Multiple stages of evolutionary change in anthrax toxin receptor expression in humans
Lauren A. Choate, Gilad Barshad, Pierce W. McMahon, Iskander Said, Edward J. Rice, Paul R. Munn, James J. Lewis, Charles G. Danko
bioRxiv 2020.07.29.227660; doi: https://doi.org/10.1101/2020.07.29.227660
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Multiple stages of evolutionary change in anthrax toxin receptor expression in humans
Lauren A. Choate, Gilad Barshad, Pierce W. McMahon, Iskander Said, Edward J. Rice, Paul R. Munn, James J. Lewis, Charles G. Danko
bioRxiv 2020.07.29.227660; doi: https://doi.org/10.1101/2020.07.29.227660

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