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

Animal husbandry and hunting has increased human exposure to pathogens. Here, the authors investigate the evolution of human host gene expression to Bacillus anthracis infection, the bacterium that causes anthrax disease. They observe recent positive selection, suggestive of human genome adaptation to anthrax disease. The advent of animal husbandry and hunting increased human exposure to zoonotic pathogens. To understand how a zoonotic disease may have influenced human evolution, we study 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 is 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 observe multiple genetic signatures consistent with recent positive selection driving a European-specific decrease in ANTXR2 expression in multiple 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.

Automated summary

The study reveals potential human genome adaptation to anthrax disease and genetic signatures indicating recent positive selection on European-specific decrease in ANTXR2 expression. This suggests that humans adapted to anthrax disease due to early ecological changes associated with hunting and scavenging, and a second period of adaptation after the rise of modern agriculture.