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

Authors

Jeffrey Vedanayagam, Sloan-Kettering Institute
Marion Herbette, Université Claude Bernard Lyon 1
Holly Mudgett, University of Nebraska-Lincoln
Ching-Jung Lin, Sloan-Kettering Institute, Weill Cornell Medical College
Chun- Ming Lai, Sloan-Kettering Institute
Caitlin McDonough-Goldstein, Syracuse University
Stephen Dorus, Syracuse University
Benjamin Loppin, Université Claude Bernard Lyon 1
Colin D. Meiklejohn, University of Nebraska-LincolnFollow
Raphaëlle Dubruille, Université Claude Bernard Lyon 1
Eric C. Lai, Sloan-Kettering Institute, Weill Cornell Medical College

Document Type

Article

Date of this Version

6-8-2023

Citation

Vedanayagam J, Herbette M, Mudgett H, Lin C-J, Lai C-M, McDonough-Goldstein C, et al. (2023) Essential and recurrent roles for hairpin RNAs in silencing de novo sex chromosome conflict in Drosophila simulans. PLoS Biol 21(6): e3002136. https://doi.org/10.1371/journal. pbio.3002136

Comments

Open access.

Abstract

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.