PT  - JOURNAL ARTICLE
AU  - Choate, Lauren A.
AU  - Barshad, Gilad
AU  - McMahon, Pierce W.
AU  - Said, Iskander
AU  - Rice, Edward J.
AU  - Munn, Paul R.
AU  - Lewis, James J.
AU  - Danko, Charles G.
TI  - Multiple stages of evolutionary change in anthrax toxin receptor expression in humans
AID  - 10.1101/2020.07.29.227660
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.07.29.227660
4099  - http://biorxiv.org/content/early/2020/07/30/2020.07.29.227660.short
4100  - http://biorxiv.org/content/early/2020/07/30/2020.07.29.227660.full
AB  - 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 StatementThe authors have declared no competing interest.