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A transcriptional switch controls sex determination in Plasmodium falciparum

Author

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  • A. R. Gomes

    (Laboratory of Pathogen Host Interactions UMR 5235, Université de Montpellier and CNRS)

  • A. Marin-Menendez

    (Université de Montpellier, IRD, CNRS)

  • S. H. Adjalley

    (Wellcome Sanger Institute)

  • C. Bardy

    (Université de Montpellier, IRD, CNRS)

  • C. Cassan

    (Université de Montpellier, IRD, CNRS)

  • M. C. S. Lee

    (Wellcome Sanger Institute)

  • A. M. Talman

    (Université de Montpellier, IRD, CNRS)

Abstract

Sexual reproduction and meiotic sex are deeply rooted in the eukaryotic tree of life, but mechanisms determining sex or mating types are extremely varied and are only well characterized in a few model organisms1. In malaria parasites, sexual reproduction coincides with transmission to the vector host. Sex determination is non-genetic, with each haploid parasite capable of producing either a male or a female gametocyte in the human host2. The hierarchy of events and molecular mechanisms that trigger sex determination and maintenance of sexual identity are yet to be elucidated. Here we show that the male development 1 (md1) gene is both necessary and sufficient for male fate determination in the human malaria parasite Plasmodium falciparum. We show that Md1 has a dual function stemming from two separate domains: in sex determination through its N terminus and in male development from its conserved C-terminal LOTUS/OST-HTH domain. We further identify a bistable switch at the md1 locus, which is coupled with sex determination and ensures that the male-determining gene is not expressed in the female lineage. We describe one of only a few known non-genetic mechanisms of sex determination in a eukaryote and highlight Md1 as a potential target for interventions that block malaria transmission.

Suggested Citation

  • A. R. Gomes & A. Marin-Menendez & S. H. Adjalley & C. Bardy & C. Cassan & M. C. S. Lee & A. M. Talman, 2022. "A transcriptional switch controls sex determination in Plasmodium falciparum," Nature, Nature, vol. 612(7940), pages 528-533, December.
    • Handle: RePEc:nat:nature:v:612:y:2022:i:7940:d:10.1038_s41586-022-05509-z
    DOI: 10.1038/s41586-022-05509-z
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    Cited by:

    1. Mubasher Mohammed & Alexis Dziedziech & Diego Macedo & Frederik Huppertz & Ylva Veith & Zoé Postel & Elena Christ & Richard Scheytt & Tanja Slotte & Johan Henriksson & Johan Ankarklev, 2024. "Single-cell transcriptomics reveal transcriptional programs underlying male and female cell fate during Plasmodium falciparum gametocytogenesis," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    2. Gayani Batugedara & Xueqing M. Lu & Borislav Hristov & Steven Abel & Zeinab Chahine & Thomas Hollin & Desiree Williams & Tina Wang & Anthony Cort & Todd Lenz & Trevor A. Thompson & Jacques Prudhomme &, 2023. "Novel insights into the role of long non-coding RNA in the human malaria parasite, Plasmodium falciparum," Nature Communications, Nature, vol. 14(1), pages 1-19, December.

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