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

Patterns of positive selection were remarkably widespread in bats and strongly supported by all phylogenetic tests. Examination of bat GC-C sequences revealed 35 codon positions with significantly elevated dN/dS values mapping exclusively to the GC-C ligand-binding domain ( Figure 1B , Table S3 ). Sequence comparisons of bat GC-C and NPR2 ligand-binding domains revealed extensive diversification in GC-C relative to the closely related paralog ( Figure S3 ). Although the structural basis of the interaction between GC-C and STa has not yet been determined, a putative ligand-binding pocket was proposed in a membrane-proximal region between residues 411-416 (ref 13 ). A cluster of seven sites with elevated dN/dS values among bats is in close proximity to this region, in addition to one site identified in our analysis of GC-C in primates ( Figure S2 ).