We found that different promoters and differential localization properties of the poison and antidote proteins both facilitate killer meiotic drive. The wtf4 gene encodes both a poison and an antidote protein on largely overlapping coding sequences. In this work we study the transcriptional regulation of wtf4, a model killer meiotic driver found in fission yeast to understand mechanisms of drive. 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. These genes can also contribute to disease, often as a result of the mechanisms they use to ensure their transmission to the next generation. This view is incomplete as ‘parasitic’ genes that provide no benefit to the organism also exist. For example, infertility can be caused by the failure of a gene that normally helps fertility. From this perspective, disease is thought to arise due to disfunction of ‘good’ genes. ![]() Genomes are often considered a collection of ‘good’ genes that provide beneficial functions for the organism. We propose that these features contribute to the evolutionary success of the wtf drivers. This transcriptional regulation, which includes the use of a critical meiotic transcription factor, likely complicates the universal suppression of wtf genes without concomitantly disrupting spore viability. In addition, we show that the Mei4 transcription factor, a master regulator of meiosis, controls the expression of the wtf4 poison transcript. We show that transcriptional timing and selective protein exclusion from developing spores ensure that all spores are exposed to Wtf4 poison, but only the spores that inherit wtf4 receive a dose of Wtf4 antidote sufficient for survival. Here, we analyze how the expression and localization of the Wtf proteins are regulated to achieve drive. wtf drivers encode both a Wtf poison protein and a Wtf antidote protein using alternative transcriptional start sites. In Schizosaccharomyces pombe, wtf meiotic drivers destroy the meiotic products (spores) that do not inherit the driver from a heterozygote, thereby reducing fertility.
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