1. Diarrheal pathogens trigger rapid evolution of the guanylate cyclase-C signaling axis in bats
- Author
-
Nels C. Elde, Sarah E. Apple, Clayton M. Carey, Michael S. Kay, and Zoe A. Hilbert
- Subjects
Diarrhea ,Sodium-Hydrogen Exchangers ,Bacterial Toxins ,Cystic Fibrosis Transmembrane Conductance Regulator ,Receptors, Enterotoxin ,Cyclic GMP-Dependent Protein Kinase Type II ,Enterotoxin ,Biology ,Microbiology ,Article ,Pathogenesis ,Enterotoxins ,chemistry.chemical_compound ,Chiroptera ,Virology ,Genetic variation ,Animals ,Enterotoxigenic Escherichia coli ,Natriuretic Peptides ,Receptor ,Cyclic GMP ,Vibrio cholerae ,Genetics ,Phylogenetic tree ,Host (biology) ,biology.organism_classification ,Enterocytes ,chemistry ,Guanylate Cyclase ,Parasitology ,Bacteria ,Protein Binding ,Signal Transduction ,Uroguanylin - Abstract
The pathogenesis of infectious diarrheal diseases is largely attributed to enterotoxins that cause dehydration by disrupting intestinal water absorption. We investigated patterns of genetic variation in mammalian guanylate cyclase-C (GC-C), an intestinal receptor targeted by bacterially encoded heat-stable enterotoxins (STa), to determine how host species adapt in response to diarrheal infections. Our phylogenetic and functional analysis of GC-C supports long-standing evolutionary conflict with diarrheal bacteria in primates and bats, with highly variable susceptibility to STa across species. In bats, we further show that GC-C diversification has sparked compensatory mutations in the endogenous uroguanylin ligand, suggesting an unusual scenario of pathogen-driven evolution of an entire signaling axis. Together, these findings suggest that conflicts with diarrheal pathogens have had far-reaching impacts on the evolution of mammalian gut physiology.
- Published
- 2021