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Published March 23, 2023 | Submitted
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Genetic control of a sex-specific piRNA program

Abstract

Sexually dimorphic traits in morphologies are widely studied, but those in essential molecular pathways remain largely unexplored. Previous work showed substantial sex differences in Drosophila gonadal piRNAs, which guide PIWI proteins to silence selfish genetic elements thereby safeguarding fertility. However, the genetic control mechanisms of piRNA sexual dimorphism remain unknown. Here, we showed that most sex differences in the piRNA program originate from the germline rather than gonadal somatic cells. Building on this, we dissected the contribution of sex chromosome and cellular sexual identity towards the sex-specific germline piRNA program. We found that the presence of the Y chromosome is sufficient to recapitulate some aspects of the male piRNA program in a female cellular environment. Meanwhile, sexual identity controls the sexually divergent piRNA production from X-linked and autosomal loci, revealing a crucial input from sex determination into piRNA biogenesis. Sexual identity regulates piRNA biogenesis through Sxl and this effect is mediated in part through chromatin proteins Phf7 and Kipferl. Together, our work delineated the genetic control of a sex-specific piRNA program, where sex chromosome and sexual identity collectively sculpt an essential molecular trait.

Additional Information

The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license. We thank Grace YC Lee, Felipe Karam Teixeira, Justin Blumenstiel, Katalin Fejes Toth, and members of the Aravin Laboratory for discussion, Jim Kennison for advice on sex chromosome nondisjunction, Mark Van Doren and Helen Salz for advice on sex determination, and Yukiko Yamashita for sharing unpublished results. We thank Angela Stathopoulos, Ellen Rothenberg, and Henry Chung for comments on the manuscript. We are grateful to Liz Gavis, Bloomington Drosophila Stock Center and Vienna Drosophila Resource Center for fly lines. We appreciate the help of Igor Antoshechkin (Millard and Muriel Jacobs Genetics and Genomics Laboratory, Caltech) with sequencing, the help of Fan Gao (Bioinformatics Resource Center, Caltech) with bioinformatic analysis, the help of Grace Shin (Molecular Technologies, Caltech) with in situ HCR, and the help of Giada Spigolon and Andres Collazo (Biological Imaging Facility, Caltech) with microscopy. This work was supported by grants from the National Institutes of Health (R01 GM097363) and by the HHMI Faculty Scholar Award to A.A.A. The authors have declared no competing interest.

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Additional details

Created:
August 20, 2023
Modified:
December 22, 2023