cam.issuedOnline	2018-08-02
dc.contributor.author	Frézal, Lise
dc.contributor.author	Demoinet, Emilie
dc.contributor.author	Braendle, Christian
dc.contributor.author	Miska, Eric
dc.contributor.author	Félix, Marie-Anne
dc.contributor.orcid	Miska, Eric [0000-0002-4450-576X]
dc.date.accessioned	2018-09-21T15:22:18Z
dc.date.available	2018-09-21T15:22:18Z
dc.date.issued	2018-08-20
dc.description.abstract	Although heredity mostly relies on the transmission of DNA sequence, additional molecular and cellular features are heritable across several generations. In the nematode Caenorhabditis elegans, insights into such unconventional inheritance result from two lines of work. First, the mortal germline (Mrt) phenotype was defined as a multigenerational phenotype whereby a selfing lineage becomes sterile after several generations, implying multigenerational memory [1, 2]. Second, certain RNAi effects are heritable over several generations in the absence of the initial trigger [3-5]. Both lines of work converged when the subset of Mrt mutants that are heat sensitive were found to closely correspond to mutants defective in the RNAi-inheritance machinery, including histone modifiers [6-9]. Here, we report the surprising finding that several C. elegans wild isolates display a heat-sensitive mortal germline phenotype in laboratory conditions: upon chronic exposure to higher temperatures, such as 25°C, lines reproducibly become sterile after several generations. This phenomenon is reversible, as it can be suppressed by temperature alternations at each generation, suggesting a non-genetic basis for the sterility. We tested whether natural variation in the temperature-induced Mrt phenotype was of genetic nature by building recombinant inbred lines between the isolates MY10 (Mrt) and JU1395 (non-Mrt). Using bulk segregant analysis, we detected two quantitative trait loci. After further recombinant mapping and genome editing, we identified the major causal locus as a polymorphism in the set-24 gene, encoding a SET- and SPK-domain protein. We conclude that C. elegans natural populations may harbor natural genetic variation in epigenetic inheritance phenomena.
dc.format.medium	Print-Electronic
dc.identifier.doi	10.17863/CAM.28012
dc.identifier.eissn	1879-0445
dc.identifier.issn	0960-9822
dc.identifier.uri	https://www.repository.cam.ac.uk/handle/1810/280646
dc.language	eng
dc.language.iso	eng
dc.publisher	Elsevier BV
dc.publisher.url	http://dx.doi.org/10.1016/j.cub.2018.05.091
dc.subject	C. elegans
dc.subject	epigenetic inheritance
dc.subject	evolution
dc.subject	mortal germline
dc.subject	quantitative genetics
dc.subject	set-24
dc.subject	Animals
dc.subject	Caenorhabditis elegans
dc.subject	Epigenesis, Genetic
dc.subject	Fertility
dc.subject	Genetic Variation
dc.subject	Hot Temperature
dc.subject	Phenotype
dc.subject	Quantitative Trait Loci
dc.title	Natural Genetic Variation in a Multigenerational Phenotype in C. elegans.
dc.type	Article
dcterms.dateAccepted	2018-05-31
prism.endingPage	2596.e8
prism.issueIdentifier	16
prism.publicationDate	2018
prism.publicationName	Curr Biol
prism.startingPage	2588
prism.volume	28
pubs.funder-project-id	Wellcome Trust (104640/Z/14/Z)
pubs.funder-project-id	Cancer Research UK (18583)
pubs.funder-project-id	Wellcome Trust (092096/Z/10/Z)
pubs.funder-project-id	Cancer Research Uk (None)
pubs.funder-project-id	Wellcome Trust (203144/Z/16/Z)
rioxxterms.licenseref.startdate	2018-08-02
rioxxterms.licenseref.uri	http://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.type	Journal Article/Review
rioxxterms.version	AM
rioxxterms.versionofrecord	10.1016/j.cub.2018.05.091

Natural Genetic Variation in a Multigenerational Phenotype in C. elegans.

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