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bioRxiv · 10.1101/2022.12.04.519051

Deregulation of Y-linked protamine-like genes in sex chromosome-biased spermatid demise

Park, J. I.·Bell, G. W.·Yamashita, Y. M.
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Abstract

Meiotic drive is a phenomenon wherein a genetic element achieves a higher rate of transmission than dictated by Mendelian segregation (1-3). One proposed mechanism for meiotic drivers to achieve biased transmission is by sabotaging essential processes of gametogenesis (e.g. spermatogenesis), leading to demise of gametes that contain their opponents (1). Studies in D. simulans have recently found that a set of meiotic driver genes contain a sequence homologous to protamines (4, 5), critical proteins that package sperm chromatin (6-8). However, the underlying mechanisms of drive and the relevance of protamine-like sequences in meiotic drive remain unknown. While studying the function of Modulo, the homolog of Nucleolin in Drosophila melanogaster (9, 10), we unexpectedly discovered Y-linked protamine genes function as a meiotic driver: we found that modulo mutants known sterility is caused by deregulation of the autosomal protamine-like gene (Mst77F) and its Y chromosome-linked homolog (Mst77Y). Modulo regulates these genes at the step of polyadenylation of the transcripts. We show that Mst77Y likely acts as a dominant-negative form of Mst77F, interfering with the process of histone-to-protamine transition, leading to nuclear decompaction. Overexpression of Mst77Y in a wild-type background is sufficient to cause nuclear decompaction and results in the biased demise of X chromosome-bearing sperm. We propose that dominant-negative protamine variants may be a common strategy found in male meiotic drive and may explain known rapid divergence of protamine genes. Significance statementProtamines are small, highly positively charged proteins that are required for packaging DNA to produce mature sperm with highly-condensed nuclei capable of fertilization. Even small changes in the dosage of protamines in humans is associated with infertility. Yet, despite their essential function, protamines are rapidly evolving. It has been speculated that protamines rapid divergence may be explained by their potential participation in genomic conflict. Our work implicates the involvement of Y chromosome-linked multicopy protamine-like genes in meiotic drive in Drosophila melanogaster. Our results suggest that dominant negative protamines can sabotage the process of nuclear compaction during spermiogenesis, revealing a potential cellular mechanism of sperm killing in meiotic drive.

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Park, J. I., Bell, G. W., Yamashita, Y. M.. 2022-12-05. Deregulation of Y-linked protamine-like genes in sex chromosome-biased spermatid demise. https://doi.org/10.1101/2022.12.04.519051

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