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Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour

Abstract

Heritable variation in behavioural traits generally has a complex genetic basis1, and thus naturally occurring polymorphisms that influence behaviour have been defined only in 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 responses6,7,8 and, although lacking the immunological memory of vertebrate adaptive immunity, shows 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. Neuron-specific rescue and ablation experiments and genetic interaction analysis indicate that HECW-1 functions in a pair of sensory neurons to inhibit P. aeruginosa lawn avoidance behaviour through inhibition of the neuropeptide receptor NPR-1 (ref. 10), 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.

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Figure 1: Natural variation in C. elegans hecw-1 modulates behavioural avoidance of P. aeruginosa.
Figure 2: HECW-1 functions in the OLL sensory neuron pair to negatively regulate pathogen avoidance behaviour.
Figure 3: The OLL sensory neuron pair negatively regulates pathogen avoidance behaviour.
Figure 4: Regulation of pathogen avoidance behaviour and survival by HECW-1 is dependent on NPR-1.

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Acknowledgements

We thank D. Denning and H. R. Horvitz for the csp-1b cDNA. We thank Y. Kohara for the hecw-1 and npr-1 cDNAs. We thank J. Meisel for sequencing of hecw-1 polymorphisms. We thank D. Ma for technical advice on laser ablation. We thank T. Schwartz for expert advice with the structural modeling of HECW-1. The hecw-1(ok1347) deletion allele was generated by the C. elegans Knockout Consortium and obtained, along with other strains used in this study, from the Caenorhabditis Genetics Center (CGC), which is supported by the NIH—National Center for Research Resources. This work was supported by NIH Grant GM084477 (to D.H.K.).

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H.C.C. and D.H.K. designed experiments, H.C.C. and J.P. performed experiments, H.C.C. and D.H.K. analyzed and interpreted the data, and H.C.C. and D.H.K. wrote the paper.

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Correspondence to Dennis H. Kim.

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Chang, H., Paek, J. & Kim, D. Natural polymorphisms in C. elegans HECW-1 E3 ligase affect pathogen avoidance behaviour. Nature 480, 525–529 (2011). https://doi.org/10.1038/nature10643

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