A Protamine Knockdown Mimics the Function ofSdinDrosophila melanogaster

Abstract

Segregation Distorter (SD) is an autosomal meiotic drive system found worldwide in natural populations of Drosophila melanogaster. This gene complex induces the preferential and nearly exclusive transmission of the SD chromosome in SD/SD+ males. This selfish propagation occurs through the interplay of the Sd locus, its enhancers and the Rsps locus during spermatid development. The key distorter locus, Sd, encodes a truncated but enzymatically active RanGAP (RanGTPase-activating protein), a key nuclear transport factor in the Ran signaling pathway. When encoded by Sd, RanGAP is mislocalized to the nucleus interior, which then traps Ran inside the nucleus and disrupts nuclear import. As a result of this aberrant nuclear transport, a process known as the histone-to-protamine transition that is required for proper spermatid condensation fails to occur in SD/SD+ males. In this process, sperm-specific protamine proteins enter the spermatid nucleus and replace the formerly chromatin-complexed histones. Previously, we have shown that mutations affecting nuclear import and export can enhance distortion in an SD background, thus verifying that a defect in nuclear transport is responsible for the unequal transmission of chromosomes. Herein, we show that specifically reducing protamines induces distortion in an SD background, verifying that protamines are transported via the RanGAP/GEF pathway and indicating that E(SD) plays a significant and unique role in the process of distortion.

Distinct spermiogenic phenotypes underlie sperm elimination in the Segregation Distorter meiotic drive system

“…In distorter males carrying a Rsp ss chromosome, compaction defects in SD + spermatids might reach a threshold that triggers their systematic elimination during the individualization process. Supporting a functional link between SD and SNBPs, knocking-down Mst35Ba/b or Mst77F induces segregation distortion in the absence of the Sd mutation but in the presence of the other SD genetic components (i.e M(SD); E(SD) and St(SD) ) [ 31 ]. This observation suggests that limiting amounts of SNBPs in a sensitized genetic background exacerbate the negative impact of the Rsp ss satDNA on sperm nuclear compaction.…”

Hybrid Sterility, Genetic Conflict and Complex Speciation: Lessons From the Drosophila simulans Clade Species

“…Processing of satDNAs during this radical chromatin remodeling appears to be susceptible to disruption. In D. melanogaster , for example, the autosomal meiotic drive gene complex Segregation Distorter ( SD ) achieves a >95% transmission advantage from heterozygous SD/ + males by disrupting the histone-to-protamine transition for + -bearing spermatids that have large blocks of Rsp satDNA ( Wu et al, 1988 ; Gingell and McLean, 2020 ). In sterile F 1 hybrid males between D. simulans and D. mauritiana , sperm nuclei show an age-dependent de-condensation phenotype ( Kanippayoor et al, 2020 ), suggestive of compromised chromatin integrity, but whether specific misregulation of satDNAs is involved is unknown.…”

Distinct spermiogenic phenotypes underlie sperm elimination in theSegregation Distortermeiotic drive system

“…In distorter males carrying a Rsp ss chromosome, compaction defects in SD + spermatids might reach a threshold that triggers their systematic elimination during the individualization process. Supporting a functional link between SD and SNBPs, knocking-down Mst35Ba/b or Mst77F induces segregation distortion in the absence of the Sd mutation but in the presence of the other SD genetic components [i.e M(SD); E(SD) and St(SD) ] (Gingell and McLean, 2020). This observation suggests that limiting amounts of SNBPs in a sensitized genetic background exacerbate the negative impact of the Rsp ss satDNA on sperm nuclear compaction.…”