Sex determination and differentiation genes identified.

Malaria parasites must switch to sexual reproduction to infect mosquitoes, but how do they decide to become male or female? How does the same transcription factor make the switch and generate both sexes? Answers are emerging from our genetic screen published today (Russell et al., 2023)

Finding genes for making transmission forms was easy: Take a line that makes green males and red females, generated barcoded mutants, sort by colour and count barcodes to see which bucket lacks which mutant. 

But is a gene needed to decide sex ratio or later, for the cell to differentiate once the decision has been taken? A much harder question, because the way we had designed the screen, all hits already affected the red and green markers. 

To find out if a sex never formed or got stuck after the initial decision, we phenotyped ten mutants by single-cell transcriptomics. This distinguished determination candidates from genes that definitely act later, during differentiation. 

Among the determination candidates are proteins that bind mRNA or other mRNA binding proteins, suggesting a posttranscriptional element to sex determination in Plasmodium

Our top male candidate, MD1, has domains used also in animal germ line definition! We are excited to see the work on MD1 in mouse malaria already followed up and expanded in a human malaria parasite by one of our co-authors (Gomes et al., 2022).

Wonderful collaboration with the labs of Mara Lawnizcak, Andy Waters and others.