Rapid Evolution of the X-Linked miR-506 Family Enhances Sperm Competitiveness and Male Reproductive Fitness

핵심 개념

The X-linked miR-506 family miRNAs, which are predominantly expressed in spermatogenic cells and sperm, have rapidly evolved across mammals. Ablation of multiple miR-506 family clusters compromises sperm competitiveness and male reproductive fitness, suggesting these miRNAs function to finetune gene expression during spermatogenesis to enhance sperm competition and male reproductive success.

초록

The content discusses the evolutionary history and functional significance of the X-linked miR-506 family of miRNAs. Key highlights:

1. The miR-506 family miRNAs are located on the X chromosome, flanked by two highly conserved protein-coding genes (Slitrk2 and Fmr1), but have rapidly evolved across eutherian mammals.
2. Tracing the evolutionary origin, the miR-506 family miRNAs were derived from the MER91C DNA transposons, which can form hairpin structures and produce mature miRNAs.
3. These miRNAs are predominantly expressed in spermatogenic cells and sperm across multiple mammalian species, suggesting a potential role in spermatogenesis and male fertility.
4. Selective deletion of individual miR-506 family miRNAs or clusters did not cause major fertility defects in mice. However, simultaneous ablation of five clusters containing 19 miR-506 family members led to reduced male fertility, manifested as smaller litter sizes.
5. Further analyses revealed that the miR-506 KO sperm were less competitive than wild-type sperm in polyandrous mating schemes, despite normal sperm counts, motility and morphology.
6. Transcriptomic and bioinformatic analyses showed the miR-506 family miRNAs target a large number of genes involved in spermatogenesis and embryonic development, and can compensate for each other's functions.
7. The rapid evolution of the miR-506 family appears to be driven by the need to target an increasing number of genes related to spermatogenesis and early embryonic development, rather than increased complexity of 3'UTRs in conserved target genes.

Overall, the data suggest the miR-506 family miRNAs function to enhance sperm competitiveness and male reproductive fitness by finetuning gene expression during spermatogenesis.

통계

The testis expresses more genes than any other organ in the body, with the possible exception of the brain.
Simultaneous ablation of five clusters containing 19 miR-506 family members led to reduced litter size in mice.
The quinKO sperm were less competitive than wild-type sperm in polyandrous mating schemes.
The human miR-506 family targets ~1,268 unique transcripts per miRNA, whereas the murine miR-506 family targets ~1,068 transcripts per miRNA.

인용구

"The X-linked miR-506 family has rapidly evolved in mammals, but their physiological significance remains elusive."
"Simultaneous ablation of five clusters containing nineteen members of the miR-506 family led to reduced male fertility in mice."
"Using experiments that mimic polyandrous mating, we found that the quinKO male mice indeed displayed compromised sperm competition."

핵심 통찰 요약

The Rapidly Evolving X-linked miR-506 Family Finetunes Spermatogenesis to Enhance Sperm Competition

by Wang,Z., Wan... 게시일 www.biorxiv.org 06-14-2023

https://www.biorxiv.org/content/10.1101/2023.06.14.544876v2

더 깊은 질문

How do the rapidly evolving miR-506 family miRNAs coordinate with other regulatory mechanisms, such as transcription factors, to fine-tune gene expression during spermatogenesis

The rapidly evolving miR-506 family miRNAs likely coordinate with other regulatory mechanisms, such as transcription factors, to fine-tune gene expression during spermatogenesis. These miRNAs, derived from the MER91C DNA transposons, target a wide range of mRNAs involved in spermatogenesis and embryonic development. By binding to the 3’UTRs of these target genes, the miR-506 family miRNAs can post-transcriptionally regulate their expression levels. This regulatory network is crucial for the precise control of gene expression during spermatogenesis, ensuring the proper development and function of male germ cells. The miR-506 family miRNAs may work in concert with transcription factors that regulate the expression of key genes involved in spermatogenesis, forming a complex regulatory network that fine-tunes gene expression at multiple levels.

What are the evolutionary pressures that have driven the rapid diversification of the miR-506 family miRNAs across mammalian species, and how do these pressures differ between humans and other mammals

The rapid diversification of the miR-506 family miRNAs across mammalian species is driven by various evolutionary pressures. One key factor is the need to adapt to the unique reproductive strategies and environmental challenges faced by different species. In humans, the pressures driving the evolution of the miR-506 family miRNAs may be influenced by factors such as changes in mating behaviors, genetic diversity, and environmental stressors. The human miR-506 family miRNAs have evolved to target a greater number of genes involved in spermatogenesis compared to other mammals, possibly reflecting the increased complexity of human reproductive biology. On the other hand, in other mammals, the evolutionary pressures shaping the miR-506 family miRNAs may be more influenced by species-specific reproductive strategies, genetic drift, and environmental adaptations. Overall, the diversification of the miR-506 family miRNAs across mammalian species reflects the dynamic interplay between genetic, environmental, and reproductive factors.

Given the role of the miR-506 family in enhancing sperm competitiveness, how might dysregulation of these miRNAs contribute to male infertility in humans, and could they serve as potential therapeutic targets

Dysregulation of the miR-506 family miRNAs could contribute to male infertility in humans by disrupting the finely tuned gene expression patterns essential for spermatogenesis and sperm competitiveness. When these miRNAs are not functioning properly, the regulatory network controlling male reproductive fitness may be compromised, leading to suboptimal sperm quality and reduced sperm competitiveness. As demonstrated in the study, knockout of the miR-506 family miRNAs in mice resulted in reduced sperm competitiveness and male subfertility, highlighting the importance of these miRNAs in male reproductive success. In humans, dysregulation of the miR-506 family miRNAs could potentially lead to similar outcomes, impacting sperm quality, sperm competitiveness, and overall male fertility. Therefore, targeting the miR-506 family miRNAs could hold promise as a potential therapeutic strategy for addressing male infertility, by restoring proper gene expression regulation during spermatogenesis and enhancing sperm competitiveness.