A natural fungal gene drive enacts killing through targeting DNA

A natural fungal gene drive enacts killing through targeting DNA

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A. S. Urquhart and D. M. Gardiner,  bioRxiv,  2022.01.19.477016. 2022.

Fungal spore-killers are a class of selfish genetic elements that positively bias their own inheritance by killing non-inheriting gametes following meiosis. As killing takes place specifically within the developing fungal ascus, a tissue which is experimentally difficult to isolate, our understanding of the mechanisms underlying spore killers are limited. In particular, how these loci kill other spores within the fungal ascus is largely unknown. Here we overcome these experimental barriers by developing model systems in two evolutionary distant organisms, Escherichia coli (bacterium) and Saccharomyces cerevisiae (yeast). Using these systems, we show that the Podospora anserina spore killer protein Spok1 enacts killing through targeting DNA.Significance Statement Natural gene drives have shaped the genomes of many eukaryotes and recently have been considered for applications to control undesirable species. In fungi these loci are called spore-killers. Despite their importance in evolutionary processes and possible applications our understanding of how they enact killing is limited. We show that the spore killer protein Spok1, which has homologues throughout the fungal tree of life, acts via DNA disruption. Spok1 is only the second spore killer locus in which the cellular target of killing has been identified and is the first known to target DNA. We also show that the DNA disrupting activity of Spok1 is functional in both bacteria and yeast suggesting a highly conserved mode of action.Competing Interest StatementThe authors have declared no competing interest.