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

Cell Host Microbe. 2023 Feb 8;31(2):305-319.e10. doi: 10.1016/j.chom.2022.12.011. Epub 2023 Jan 11.

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.

Keywords: Plasmodium; development; differentiation; malaria; sex determination; sex ratio; single cell analysis; transmission.

MeSH terms

  • Animals
  • Culicidae* / parasitology
  • Female
  • Malaria* / parasitology
  • Male
  • Parasites* / metabolism
  • Plasmodium berghei / genetics
  • Protozoan Proteins / genetics
  • Protozoan Proteins / metabolism
  • Sexual Development / genetics

Substances

  • Protozoan Proteins