Sex-specific splicing occurs genome-wide during early Drosophila embryogenesis

Abstract

Sex-specific splicing is an essential process that regulates sex determination and drives sexual dimorphism. Yet, how early in development widespread sex-specific transcript diversity occurs was unknown because it had yet to be studied at the genome-wide level. We use the powerful Drosophila model to show that widespread sex-specific transcript diversity occurs early in development, concurrent with zygotic genome activation. We also present a new pipeline called time2splice to quantify changes in alternative splicing over time. Furthermore, we determine that one of the consequences of losing an essential maternally-deposited pioneer factor called CLAMP (Chromatin linked adapter for MSL proteins) is altered sex-specific splicing of genes involved in diverse biological processes that drive development. Overall, we show that sex-specific differences in transcript diversity exist even at the earliest stages of development.

Data availability

Sequencing data have been deposited in GEO under accession codes #GSE220455 and #GSE220439All data generated or analyzed during this study are included in the manuscript and supporting file; Source Data files have been provided for Figures 2-figure Supplement 3, Figure 5, and Figure 6Source data used to generate all the figures, graphs, and Venn diagrams are provided in Supplementary Data Tables S1-S7

The following data sets were generated
The following previously published data sets were used

Article and author information

Author details

  1. Mukulika Ray

    Molecular Biology, Cellular Biology and Biochemistry Department, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9064-818X
  2. Ashley Mae Conard

    Center for Computational Molecular Biology, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Jennifer Urban

    Biology Department, Johns Hopkins University, Baltimore, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6621-8358
  4. Pranav Mahableshwarkar

    Center for Computational Molecular Biology, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Joseph Aguilera

    Molecular Biology, Cellular Biology and Biochemistry Department, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Annie Huang

    Molecular Biology, Cellular Biology and Biochemistry Department, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Smriti Vaidyanathan

    Center for Computational Molecular Biology, Brown University, Providence, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Erica Larschan

    Molecular Biology, Cellular Biology and Biochemistry, Brown University, Providence, United States
    For correspondence
    erica_larschan@brown.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2484-4921

Funding

National Institute of General Medical Sciences (R35GM126994)

  • Mukulika Ray
  • Erica Larschan

National Science Foundation (Graduate Research Fellowship)

  • Ashley Mae Conard

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Luisa Cochella, Johns Hopkins University, United States

Version history

  1. Preprint posted: March 19, 2021 (view preprint)
  2. Received: March 17, 2023
  3. Accepted: July 11, 2023
  4. Accepted Manuscript published: July 19, 2023 (version 1)
  5. Version of Record published: August 3, 2023 (version 2)

Copyright

© 2023, Ray et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Mukulika Ray
  2. Ashley Mae Conard
  3. Jennifer Urban
  4. Pranav Mahableshwarkar
  5. Joseph Aguilera
  6. Annie Huang
  7. Smriti Vaidyanathan
  8. Erica Larschan
(2023)
Sex-specific splicing occurs genome-wide during early Drosophila embryogenesis
eLife 12:e87865.
https://doi.org/10.7554/eLife.87865

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https://doi.org/10.7554/eLife.87865

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