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Natural variation in the irld gene family affects insulin/IGF signaling and starvation resistance

Webster, Amy K. and Chitrakar, Rojin and Powell, Maya and Chen, Jingxian and Fisher, Kinsey and Tanny, Robyn and Stevens, Lewis and Evans, Kathryn and Antoshechkin, Igor and Andersen, Erik C. and Baugh, L. Ryan (2021) Natural variation in the irld gene family affects insulin/IGF signaling and starvation resistance. . (Unpublished)

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Starvation resistance is a fundamental, disease-relevant trait, but the genetic basis of its natural variation is unknown. We developed a synthetic population-sequencing approach to measure starvation resistance for many wild C. elegans strains simultaneously. We identified three quantitative trait loci with variants in 16 insulin/EGF receptor-like domain (irld) family members. We show that four irld genes affect starvation resistance by regulating insulin/IGF signaling. We propose that IRLD proteins bind insulin-like peptides to modify signaling in the sensory nervous system thereby affecting organismal physiology. This work demonstrates efficacy of using population sequencing to dissect a complex trait, identifies irld genes that regulate insulin/IGF signaling, and shows that an expanded gene family modifies a deeply conserved signaling pathway to affect a fitness-proximal trait.

Item Type:Report or Paper (Discussion Paper)
Related URLs:
URLURL TypeDescription Paper
Webster, Amy K.0000-0003-4302-8102
Andersen, Erik C.0000-0003-0229-9651
Additional Information:The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. This version posted June 7, 2021. We thank Oliver Hobert for providing OH16024 daf-16(ot971[daf-16::GFP]), Jon Hibshman for sharing a starvation survival curve-fitting script, Chelsea Shoben for help passaging wild isolates, Clay Dilks for CRISPR advice, and Jim Jordan for helpful discussions. Funding was provided by the NIH (R01GM117408 to LRB and R01ES02993 to ECA and LRB). AKW was supported by an NSF Graduate Research Fellowship. Some strains were provided by the CGC, which is funded by NIH Office of Research Infrastructure Programs (P40 OD010440). We would also like to thank WormBase. Author contributions: Conceptualization: AKW, LRB. Investigation: AKW, RC, MP, JC, KF, RT. Formal analysis: AKW, LS, KE, IA. Visualization: AKW. Funding acquisition: LRB, ECA. Supervision: LRB, ECA. Writing – original draft: AKW, LRB. Writing – review & editing: AKW, LRB, ECA, RC, KE, IA. The authors have declared no competing interest.
Funding AgencyGrant Number
NSF Graduate Research FellowshipUNSPECIFIED
NIHP40 OD010440
Record Number:CaltechAUTHORS:20210610-072409155
Persistent URL:
Official Citation:Natural variation in the irld gene family affects insulin/IGF signaling and starvation resistance. Amy K. Webster, Rojin Chitrakar, Maya Powell, Jingxian Chen, Kinsey Fisher, Robyn Tanny, Lewis Stevens, Kathryn Evans, Igor Antoshechkin, Erik C. Andersen, L. Ryan Baugh. bioRxiv 2021.06.07.447366; doi:
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:109458
Deposited By: Tony Diaz
Deposited On:10 Jun 2021 16:49
Last Modified:16 Nov 2021 19:36

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