Mutation, selection, and quantitative genetic architecture of susceptibility to bacterial pathogens in C. elegans

Understanding the evolutionary and genetic underpinnings of susceptibility to pathogens is of fundamental importance across a wide swathe of biology. Much theoretical and empirical effort has focused on genetic variants of large effect, but pathogen susceptibility often appears to be a polygenic complex trait. Here we investigate the quantitative genetics of survival over 120 hours of exposure ("susceptibility") of C. elegans to three bacterial pathogens of varying virulence, along with the non-pathogenic OP50 strain of E. coli. We compare the genetic (co)variance input by spontaneous mutations accumulated under minimal selection to the standing genetic (co)variance in a set of ~50 wild isolates. Three conclusions emerge. First, with one exception, mutations increase susceptibility to pathogens, and susceptibility is uncorrelated with fitness in the absence of pathogens. Second, the orientation in trait space of the heritable (co)variance of wild isolates is sufficiently explained by mutation. However, pathogen susceptibility is clearly under purifying, apparently directional, selection of magnitude similar to that of competitive fitness in the MA conditions. The results provide no evidence for fitness tradeoffs between pathogen susceptibility and fitness in the absence of pathogens, nor that balancing selection is important in maintaining genetic variation for susceptibility to these bacterial pathogens.