available in PMC 2012 June 22.Heritable variation in behavioural traits generally has a complex genetic basis1, and thus naturally
occurring polymorphisms that influence behaviour have been defined in only rare instances2,3.
The isolation of wild strains of Caenorhabditis elegans has facilitated the study of natural genetic
variation in this species4 and provided insights into its diverse microbial ecology5. C. elegans
responds to bacterial infection with conserved innate immune responses6-8 and, while lacking the
immunological memory of vertebrate adaptive immunity, exhibits an aversive learning response to
pathogenic bacteria9. Here, we report the molecular characterization of naturally occurring coding
polymorphisms in a C. elegans gene encoding a conserved HECT domain-containing E3 ubiquitin
ligase, HECW-1. We show that two distinct polymorphisms in neighbouring residues of HECW-1
each affect C. elegans behavioural avoidance of a lawn of Pseudomonas aeruginosa. Neuronspecific
rescue and ablation experiments, and genetic interaction analysis suggest that HECW-1
functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through
inhibition of the neuropeptide receptor NPR-110, which we have previously shown promotes P.
aeruginosa lawn avoidance behaviour11. Our data establish a molecular basis for natural variation
in a C. elegans behaviour that may undergo adaptive changes in response to microbial pathogens.National Institutes of Health (U.S.) (NIH Grant GM084477
