RT Journal Article
SR Electronic
T1 Multiple stages of evolutionary change in anthrax toxin receptor expression in humans
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2020.07.29.227660
DO 10.1101/2020.07.29.227660
A1 Choate, Lauren A.
A1 Barshad, Gilad
A1 McMahon, Pierce W.
A1 Said, Iskander
A1 Rice, Edward J.
A1 Munn, Paul R.
A1 Lewis, James J.
A1 Danko, Charles G.
YR 2020
UL http://biorxiv.org/content/early/2020/07/30/2020.07.29.227660.abstract
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.