Natural variation in the irld gene family affects insulin/IGF signaling and starvation resistance
Abstract
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.
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.Attached Files
Submitted - 2021.06.07.447366v1.full.pdf
Supplemental Material - media-1.xlsx
Supplemental Material - media-2.xlsx
Supplemental Material - media-3.xlsx
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Additional details
- Eprint ID
- 109458
- Resolver ID
- CaltechAUTHORS:20210610-072409155
- R01GM117408
- NIH
- R01ES02993
- NIH
- NSF Graduate Research Fellowship
- P40 OD010440
- NIH
- Created
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2021-06-10Created from EPrint's datestamp field
- Updated
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2021-11-16Created from EPrint's last_modified field