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Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans

Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms...

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Autores principales: Vedanayagam, Jeffrey, Herbette, Marion, Mudgett, Holly, Lin, Ching-Jung, Lai, Chun-Ming, McDonough-Goldstein, Caitlin, Dorus, Stephen, Loppin, Benjamin, Meiklejohn, Colin, Dubruille, Raphaëlle, Lai, Eric C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292708/
https://www.ncbi.nlm.nih.gov/pubmed/37289846
http://dx.doi.org/10.1371/journal.pbio.3002136
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author Vedanayagam, Jeffrey
Herbette, Marion
Mudgett, Holly
Lin, Ching-Jung
Lai, Chun-Ming
McDonough-Goldstein, Caitlin
Dorus, Stephen
Loppin, Benjamin
Meiklejohn, Colin
Dubruille, Raphaëlle
Lai, Eric C.
author_facet Vedanayagam, Jeffrey
Herbette, Marion
Mudgett, Holly
Lin, Ching-Jung
Lai, Chun-Ming
McDonough-Goldstein, Caitlin
Dorus, Stephen
Loppin, Benjamin
Meiklejohn, Colin
Dubruille, Raphaëlle
Lai, Eric C.
author_sort Vedanayagam, Jeffrey
collection PubMed
description Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms that can suppress their activity. Here, we present data from the fruitfly Drosophila simulans that address these questions. We show that a family of de novo, protamine-derived X-linked selfish genes (the Dox gene family) is silenced by a pair of newly emerged hairpin RNA (hpRNA) small interfering RNA (siRNA)-class loci, Nmy and Tmy. In the w[XD1] genetic background, knockout of nmy derepresses Dox and MDox in testes and depletes male progeny, whereas knockout of tmy causes misexpression of PDox genes and renders males sterile. Importantly, genetic interactions between nmy and tmy mutant alleles reveal that Tmy also specifically maintains male progeny for normal sex ratio. We show the Dox loci are functionally polymorphic within D. simulans, such that both nmy-associated sex ratio bias and tmy-associated sterility can be rescued by wild-type X chromosomes bearing natural deletions in different Dox family genes. Finally, using tagged transgenes of Dox and PDox2, we provide the first experimental evidence Dox family genes encode proteins that are strongly derepressed in cognate hpRNA mutants. Altogether, these studies support a model in which protamine-derived drivers and hpRNA suppressors drive repeated cycles of sex chromosome conflict and resolution that shape genome evolution and the genetic control of male gametogenesis.
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spelling pubmed-102927082023-06-27 Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans Vedanayagam, Jeffrey Herbette, Marion Mudgett, Holly Lin, Ching-Jung Lai, Chun-Ming McDonough-Goldstein, Caitlin Dorus, Stephen Loppin, Benjamin Meiklejohn, Colin Dubruille, Raphaëlle Lai, Eric C. PLoS Biol Research Article Meiotic drive loci distort the normally equal segregation of alleles, which benefits their own transmission even in the face of severe fitness costs to their host organism. However, relatively little is known about the molecular identity of meiotic drivers, their strategies of action, and mechanisms that can suppress their activity. Here, we present data from the fruitfly Drosophila simulans that address these questions. We show that a family of de novo, protamine-derived X-linked selfish genes (the Dox gene family) is silenced by a pair of newly emerged hairpin RNA (hpRNA) small interfering RNA (siRNA)-class loci, Nmy and Tmy. In the w[XD1] genetic background, knockout of nmy derepresses Dox and MDox in testes and depletes male progeny, whereas knockout of tmy causes misexpression of PDox genes and renders males sterile. Importantly, genetic interactions between nmy and tmy mutant alleles reveal that Tmy also specifically maintains male progeny for normal sex ratio. We show the Dox loci are functionally polymorphic within D. simulans, such that both nmy-associated sex ratio bias and tmy-associated sterility can be rescued by wild-type X chromosomes bearing natural deletions in different Dox family genes. Finally, using tagged transgenes of Dox and PDox2, we provide the first experimental evidence Dox family genes encode proteins that are strongly derepressed in cognate hpRNA mutants. Altogether, these studies support a model in which protamine-derived drivers and hpRNA suppressors drive repeated cycles of sex chromosome conflict and resolution that shape genome evolution and the genetic control of male gametogenesis. Public Library of Science 2023-06-08 /pmc/articles/PMC10292708/ /pubmed/37289846 http://dx.doi.org/10.1371/journal.pbio.3002136 Text en © 2023 Vedanayagam et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Vedanayagam, Jeffrey
Herbette, Marion
Mudgett, Holly
Lin, Ching-Jung
Lai, Chun-Ming
McDonough-Goldstein, Caitlin
Dorus, Stephen
Loppin, Benjamin
Meiklejohn, Colin
Dubruille, Raphaëlle
Lai, Eric C.
Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans
title Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans
title_full Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans
title_fullStr Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans
title_full_unstemmed Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans
title_short Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans
title_sort essential and recurrent roles for hairpin rnas in silencing de novo sex chromosome conflict in drosophila simulans
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10292708/
https://www.ncbi.nlm.nih.gov/pubmed/37289846
http://dx.doi.org/10.1371/journal.pbio.3002136
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