Regulators of male and female sexual development are critical for the transmission of a malaria parasite.

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Authors

Russell, AJC
Sanderson, T
Bushell, E
Talman, AM
Anar, B
Girling, G
Hunziker, M
Kent, RS
Martin, JS
Metcalf, T
Montandon, R
Pandey, V
Pardo, M
Roberts, AB
Sayers, C
Schwach, F
Choudhary, JS
Rayner, JC
Voet, T
Modrzynska, KK
Waters, AP
Lawniczak, MKN
Billker, O

Document Type

Journal Article

Date

2023-02-08

Date Accepted

2022-12-12

Abstract

Malaria transmission to mosquitoes requires a developmental switch in asexually dividing blood-stage parasites to sexual reproduction. In Plasmodium berghei, the transcription factor AP2-G is required and sufficient for this switch, but how a particular sex is determined in a haploid parasite remains unknown. Using a global screen of barcoded mutants, we here identify genes essential for the formation of either male or female sexual forms and validate their importance for transmission. High-resolution single-cell transcriptomics of ten mutant parasites portrays the developmental bifurcation and reveals a regulatory cascade of putative gene functions in the determination and subsequent differentiation of each sex. A male-determining gene with a LOTUS/OST-HTH domain as well as the protein interactors of a female-determining zinc-finger protein indicate that germ-granule-like ribonucleoprotein complexes complement transcriptional processes in the regulation of both male and female development of a malaria parasite.

Citation

Cell Host and Microbe, 2023, 31 (2), pp. 305 - +

Source Title

Cell Host and Microbe

Publisher

CELL PRESS

ISSN

1931-3128

eISSN

1934-6069
1934-6069

Research Team

Functional Proteomics

Notes