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Cited by 22Malaria Research and ControlMicrotubule and mitosis dynamicsBird parasitology and diseases

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Systematic screens for fertility genes essential for malaria parasite transmission reveal conserved aspects of sex in a divergent eukaryote

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Sayers, Claire, Pandey, Vikash, Balakrishnan, Arjun, Michie, Katharine, Svedberg, Dennis, Hunziker, Mirjam, Pardo, Mercedes, Choudhary, Jyoti, Berntsson, Ronnie, Billker, Oliver·2024·Cell Systems
DOI 10.1016/j.cels.2024.10.008

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Abstract

Sexual reproduction in malaria parasites is essential for their transmission to mosquitoes and offers a divergent eukaryote model to understand the evolution of sex. Through a panel of genetic screens in Plasmodium berghei, we identify 348 sex and transmission-related genes and define roles for unstudied genes as putative targets for transmission-blocking interventions. The functional data provide a deeper understanding of female metabolic reprogramming, meiosis, and the axoneme. We identify a complex of a SUN domain protein (SUN1) and a putative allantoicase (ALLC1) that is essential for male fertility by linking the microtubule organizing center to the nuclear envelope and enabling mitotic spindle formation during male gametogenesis. Both proteins have orthologs in mouse testis, and the data raise the possibility of an ancient role for atypical SUN domain proteins in coupling the nucleus and axoneme. Altogether, our data provide an unbiased picture of the molecular processes that underpin malaria parasite transmission. A record of this paper's transparent peer review process is included in the supplemental information.

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Metadata

Authors
Sayers, C., Pandey, V., Balakrishnan, A., Michie, K., Svedberg, D., Hunziker, M., Pardo, M., Choudhary, J., Berntsson, R., & Billker, O.
Affiliations
  • UNSW Sydney (AU)
  • Umeå University (SE)
  • Institute of Cancer Research (GB)
Corresponding author
Billker, Oliver
ORCID
Venue
Cell Systems
Publisher
Elsevier BV
Published
2024-11
Volume
15
Issue
11
Pages
1075-1091.e6
ISSN
2405-4712 (ISSN-L)
DOI
10.1016/j.cels.2024.10.008
OpenAlex
W4404319662
Cited by
22
References
4
Citations by year
2026: 7 · 2025: 15
FWCI
9.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Cell Systems (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • KTH Publication Database DiVA (KTH Royal Institute of Technology) (submittedVersion, other-oa)
Funders
  • Wellcome Trust (206194/Z/17/Z)
  • European Research Council (788516)
  • Swiss National Science Foundation (P2SKP3_187635)
  • Human Frontier Science Program (LT000131/2020-L)
  • EU Framework Programme for Research and Innovation Marie Skłodowska-Curie Actions (895744)
  • Knut and Alice Wallenberg Foundation
  • Umeå Universitet
  • University of New South Wales
  • Svensk Njurmedicinsk Förening
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Malaria Research and Control
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Microtubule and mitosis dynamics
  • Life Sciences › Immunology and Microbiology › Parasitology › Bird parasitology and diseases
Keywords
Plasmodium berghei, male fertility, SUN domain proteins, SUN1, allantoicase, microtubule organizing center, nuclear envelope, mitotic spindle formation, male gametogenesis, meiosis, axoneme, evolution of sex, genetic screen
MeSH terms
Animals, Female, Fertility, Malaria, Male, Plasmodium berghei, Protozoan Proteins, Mice

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