Conflicts with diarrheal pathogens trigger rapid evolution of an intestinal signaling axis

Clayton M. Carey; Sarah E. Apple; Zoe A. Hilbert; Michael S. Kay; Nels C. Elde

Our work reveals how genes involved in intestinal water physiology can rapidly adapt in ongoing conflict with enteric pathogens. Similar to well established conflicts between host immune defenses and pathogen effectors, the recurrent evolutionary innovation seen in the GC-C ligand-binding domain indicates that modulating interactions with bacterial toxins has been critical for survival in primates and bats. We show that this diversification in the molecular machinery of the intestine likely contributes to disease susceptibility in host species and may restrict the host range of STa producing pathogens. Our observation of remarkable diversification at the GC-C receptor-ligand interface in bats further suggests that pathogens can spark compensatory coevolution within host . CC-BY-NC-ND 4.0 International license author/funder. It is made available under a The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.29.014761 doi: bioRxiv preprint signaling pathways. Together these findings illustrate the far-reaching impacts of deadly diarrheal infections on the evolutionary history of diverse mammals.