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dc.contributor.authorCavassim, Maria Izabel A
dc.contributor.authorBaker, Zachary
dc.contributor.authorHoge, Carla
dc.contributor.authorSchierup, Mikkel H
dc.contributor.authorSchumer, Molly
dc.contributor.authorPrzeworski, Molly
dc.date.accessioned2022-03-30T01:02:22Z
dc.date.available2022-03-30T01:02:22Z
dc.date.issued2022-03-01
dc.identifier.issn0027-8424
dc.identifier.other35217607
dc.identifier.otherPMC8892340
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/335499
dc.description.abstractIn most mammals and likely throughout vertebrates, the gene PRDM9 specifies the locations of meiotic double strand breaks; in mice and humans at least, it also aids in their repair. For both roles, many of the molecular partners remain unknown. Here, we take a phylogenetic approach to identify genes that may be interacting with PRDM9 by leveraging the fact that PRDM9 arose before the origin of vertebrates but was lost many times, either partially or entirely-and with it, its role in recombination. As a first step, we characterize PRDM9 domain composition across 446 vertebrate species, inferring at least 13 independent losses. We then use the interdigitation of PRDM9 orthologs across vertebrates to test whether it coevolved with any of 241 candidate genes coexpressed with PRDM9 in mice or associated with recombination phenotypes in mammals. Accounting for the phylogenetic relationship among a subsample of 189 species, we find two genes whose presence and absence is unexpectedly coincident with that of PRDM9: ZCWPW1, which was recently shown to facilitate double strand break repair, and its paralog ZCWPW2, as well as, more tentatively, TEX15 and FBXO47 ZCWPW2 is expected to be recruited to sites of PRDM9 binding; its tight coevolution with PRDM9 across vertebrates suggests that it is a key interactor within mammals and beyond, with a role either in recruiting the recombination machinery or in double strand break repair.
dc.languageeng
dc.publisherProceedings of the National Academy of Sciences
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourceessn: 1091-6490
dc.sourcenlmid: 7505876
dc.subjectGenetics
dc.subjectRecombination
dc.subjectComparative genomics
dc.subjectphylogenetics
dc.subjectPrdm9 Evolution
dc.subjectAnimals
dc.subjectHumans
dc.subjectMice
dc.subjectHistone-Lysine N-Methyltransferase
dc.subjectCell Cycle Proteins
dc.subjectSequence Analysis, RNA
dc.subjectEvolution, Molecular
dc.subjectPhylogeny
dc.subjectGene Deletion
dc.subjectRecombination, Genetic
dc.titlePRDM9 losses in vertebrates are coupled to those of paralogs ZCWPW1 and ZCWPW2.
dc.typeArticle
dc.date.updated2022-03-30T01:02:22Z
prism.issueIdentifier9
prism.publicationNameProc Natl Acad Sci U S A
prism.volume119
dc.identifier.doi10.17863/CAM.82930
dcterms.dateAccepted2022-01-16
rioxxterms.versionofrecord10.1073/pnas.2114401119
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidCavassim, Maria Izabel A [0000-0001-9726-1431]
dc.contributor.orcidBaker, Zachary [0000-0002-1540-0731]
dc.contributor.orcidHoge, Carla [0000-0001-9798-9684]
dc.contributor.orcidSchierup, Mikkel H [0000-0002-5028-1790]
dc.contributor.orcidPrzeworski, Molly [0000-0002-5369-9009]
dc.identifier.eissn1091-6490
pubs.funder-project-idNIH (1R35GM133774)
pubs.funder-project-idRO1 (GM83098)
pubs.funder-project-idNIGMS NIH HHS (R35 GM133774, R01 GM083098)
cam.issuedOnline2022-02-25


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Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International