S. pombe wtf drivers use dual transcriptional regulation and selective protein exclusion from spores to cause meiotic drive

N. L. Nuckolls, A. Nidamangala Srinivasa, A. C. Mok, R. M. Helston, M. A. Bravo Núñez, J. J. Lange, T. J. Gallagher, C. W. Seidel and S. E. Zanders,  PLOS Genetics,  18:e1009847. 2022.

Author summary Genomes are often considered a collection of ‘good’ genes that provide beneficial functions for the organism. From this perspective, disease is thought to arise due to disfunction of ‘good’ genes. For example, infertility can be caused by the failure of a gene that normally helps fertility. This view is incomplete as ‘parasitic’ genes that provide no benefit to the organism also exist. These genes can also contribute to disease, often as a result of the mechanisms they use to ensure their transmission to the next generation. For example, killer meiotic drivers are found throughout eukaryotes and contribute to infertility by actively destroying the gametes (e.g., egg and sperm) that do not inherit them. In this work we study the transcriptional regulation of wtf4, a model killer meiotic driver found in fission yeast to understand mechanisms of drive. The wtf4 gene encodes both a poison and an antidote protein on largely overlapping coding sequences. We found that different promoters and differential localization properties of the poison and antidote proteins both facilitate killer meiotic drive. We also found that the expression of the poison protein relies on a key transcription factor essential for gametogenesis. The use of this transcription factor likely complicates suppressing wtf4 without compromising gametogenesis. This feature likely contributes to the evolutionary success of the wtf drivers, which are found in many copies in fission yeast genomes.

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