Cumulative effects of mutation and selection on susceptibility to bacterial pathogens in Caenorhabditis 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 h of exposure ("susceptibility") of Caenorhabditis elegans to three bacterial species of varying virulence, along with a fourth strain, the OP50 strain of Escherichia coli, the standard laboratory food for C. elegans. We compare the genetic (co)variance input by spontaneous mutations accumulated under minimal selection to the standing genetic (co)variance in a set of 47 wild isolates. Three conclusions emerge. First, mutations increase susceptibility to pathogens. Second, susceptibility to pathogens is uncorrelated with fitness in the absence of pathogens. Third, with the possible exception of Staphylococcus aureus, pathogen susceptibility is clearly under purifying directional selection of magnitude roughly similar to that of competitive fitness in the mutation accumulation conditions. The results provide no evidence for fitness tradeoffs between pathogen susceptibility and fitness in the absence of pathogens.