Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegans
Starvation resistance is important to disease and fitness, but the genetic basis of its natural variation is unknown. Uncovering the genetic basis of complex, quantitative traits such as starvation resistance is technically challenging. We developed a synthetic-population (re)sequencing approach usi...
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2022-06-01
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| Series: | eLife |
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| Online Access: | https://elifesciences.org/articles/80204 |
| _version_ | 1818018310809190400 |
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| author | Amy K Webster Rojin Chitrakar Maya Powell Jingxian Chen Kinsey Fisher Robyn E Tanny Lewis Stevens Kathryn Evans Angela Wei Igor Antoshechkin Erik C Andersen L Ryan Baugh |
| author_facet | Amy K Webster Rojin Chitrakar Maya Powell Jingxian Chen Kinsey Fisher Robyn E Tanny Lewis Stevens Kathryn Evans Angela Wei Igor Antoshechkin Erik C Andersen L Ryan Baugh |
| author_sort | Amy K Webster |
| collection | DOAJ |
| description | Starvation resistance is important to disease and fitness, but the genetic basis of its natural variation is unknown. Uncovering the genetic basis of complex, quantitative traits such as starvation resistance is technically challenging. We developed a synthetic-population (re)sequencing approach using molecular inversion probes (MIP-seq) to measure relative fitness during and after larval starvation in Caenorhabditis elegans. We applied this competitive assay to 100 genetically diverse, sequenced, wild strains, revealing natural variation in starvation resistance. We confirmed that the most starvation-resistant strains survive and recover from starvation better than the most starvation-sensitive strains using standard assays. We performed genome-wide association (GWA) with the MIP-seq trait data and identified three quantitative trait loci (QTL) for starvation resistance, and we created near isogenic lines (NILs) to validate the effect of these QTL on the trait. These QTL contain numerous candidate genes including several members of the Insulin/EGF Receptor-L Domain (irld) family. We used genome editing to show that four different irld genes have modest effects on starvation resistance. Natural variants of irld-39 and irld-52 affect starvation resistance, and increased resistance of the irld-39; irld-52 double mutant depends on daf-16/FoxO. DAF-16/FoxO is a widely conserved transcriptional effector of insulin/IGF signaling (IIS), and these results suggest that IRLD proteins modify IIS, although they may act through other mechanisms as well. This work demonstrates efficacy of using MIP-seq to dissect a complex trait and it suggests that irld genes are natural modifiers of starvation resistance in C. elegans. |
| first_indexed | 2024-04-14T07:38:14Z |
| format | Article |
| id | doaj.art-0bf74f246fef489fb08c88cf69117c1d |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-14T07:38:14Z |
| publishDate | 2022-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-0bf74f246fef489fb08c88cf69117c1d2022-12-22T02:05:37ZengeLife Sciences Publications LtdeLife2050-084X2022-06-011110.7554/eLife.80204Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegansAmy K Webster0https://orcid.org/0000-0003-4302-8102Rojin Chitrakar1Maya Powell2Jingxian Chen3Kinsey Fisher4Robyn E Tanny5Lewis Stevens6Kathryn Evans7Angela Wei8Igor Antoshechkin9Erik C Andersen10https://orcid.org/0000-0003-0229-9651L Ryan Baugh11https://orcid.org/0000-0003-2148-5492Department of Biology, Duke University, Durham, United StatesDepartment of Biology, Duke University, Durham, United StatesDepartment of Biology, Duke University, Durham, United StatesDepartment of Biology, Duke University, Durham, United StatesDepartment of Biology, Duke University, Durham, United StatesDepartment of Molecular Biosciences, Northwestern University, Evanston, United StatesDepartment of Molecular Biosciences, Northwestern University, Evanston, United StatesDepartment of Molecular Biosciences, Northwestern University, Evanston, United StatesDepartment of Biology, Duke University, Durham, United StatesDivision of Biology, California Institute of Technology, Pasadena, United StatesDepartment of Molecular Biosciences, Northwestern University, Evanston, United StatesDepartment of Biology, Duke University, Durham, United States; Center for Genomic and Computational Biology, Duke University, Durham, United StatesStarvation resistance is important to disease and fitness, but the genetic basis of its natural variation is unknown. Uncovering the genetic basis of complex, quantitative traits such as starvation resistance is technically challenging. We developed a synthetic-population (re)sequencing approach using molecular inversion probes (MIP-seq) to measure relative fitness during and after larval starvation in Caenorhabditis elegans. We applied this competitive assay to 100 genetically diverse, sequenced, wild strains, revealing natural variation in starvation resistance. We confirmed that the most starvation-resistant strains survive and recover from starvation better than the most starvation-sensitive strains using standard assays. We performed genome-wide association (GWA) with the MIP-seq trait data and identified three quantitative trait loci (QTL) for starvation resistance, and we created near isogenic lines (NILs) to validate the effect of these QTL on the trait. These QTL contain numerous candidate genes including several members of the Insulin/EGF Receptor-L Domain (irld) family. We used genome editing to show that four different irld genes have modest effects on starvation resistance. Natural variants of irld-39 and irld-52 affect starvation resistance, and increased resistance of the irld-39; irld-52 double mutant depends on daf-16/FoxO. DAF-16/FoxO is a widely conserved transcriptional effector of insulin/IGF signaling (IIS), and these results suggest that IRLD proteins modify IIS, although they may act through other mechanisms as well. This work demonstrates efficacy of using MIP-seq to dissect a complex trait and it suggests that irld genes are natural modifiers of starvation resistance in C. elegans.https://elifesciences.org/articles/80204L1 arrestdiapausestarvationirldinsulinmolecular inversion probe |
| spellingShingle | Amy K Webster Rojin Chitrakar Maya Powell Jingxian Chen Kinsey Fisher Robyn E Tanny Lewis Stevens Kathryn Evans Angela Wei Igor Antoshechkin Erik C Andersen L Ryan Baugh Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegans eLife L1 arrest diapause starvation irld insulin molecular inversion probe |
| title | Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegans |
| title_full | Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegans |
| title_fullStr | Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegans |
| title_full_unstemmed | Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegans |
| title_short | Using population selection and sequencing to characterize natural variation of starvation resistance in Caenorhabditis elegans |
| title_sort | using population selection and sequencing to characterize natural variation of starvation resistance in caenorhabditis elegans |
| topic | L1 arrest diapause starvation irld insulin molecular inversion probe |
| url | https://elifesciences.org/articles/80204 |
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