海德堡大学Henrik Kaessmann研究组宣布他们开发出一个雄性必需的miRNA是鸟类性染色体剂量补偿的关键。相关论文于2025年7月16日发表在《自然》杂志上。

在这里，该课题组研究人员报道了一种具有强烈雄性偏向性表达的Z-linked microRNA （miR-2954）的体内功能和进化分析，该RNA 先前被认为可以介导鸟类性染色体剂量补偿。该研究组在鸡中敲除miR-2954，导致纯合子敲除的雄性早期胚胎致死，这可能是由剂量敏感的z连锁靶基因特异性上调驱动的。进化基因表达分析进一步表明，这些剂量敏感靶基因在雌鸟的单Z基因上发生转录和翻译上调。

总之，这项工作揭示了W基因丢失后的进化压力驱动了雌性中剂量敏感的Z连锁基因的转录和翻译上调，以及雄性中它们的转录上调。在雄性中，由于两个剂量敏感的Z基因拷贝的联合活性上调而导致的转录本过剩，反过来又被鸟类进化过程中高度靶向的miR-2954介导的转录本降解机制的出现所抵消。这项研究揭示了鸟类独特的性染色体剂量补偿系统，其中一个microRNA已成为雄性生存所必需的。

据悉，鸟类的性染色体系统中，雌性是异配型（ZW），雄性是同配型（ZZ）。鸟类性染色体与祖先常染色体的分化导致W染色体上大部分基因在进化过程中丢失。然而，在何种程度上进化的机制来抵消这种女性基因剂量的大幅减少仍然不清楚。

附：英文原文

Title: A male-essential miRNA is key for avian sex chromosome dosage compensation

Author: Fallahshahroudi, Amir, Yousefi Taemeh, Sara, Rodrguez-Montes, Leticia, Trost, Nils, Frank, Dana, Lafrenz, Pascal, Koubek, Jiri, Tellez, Guillermo, Ballantyne, Maeve, Idoko-Akoh, Alewo, Taylor, Lorna, Sherman, Adrian, Davey, Megan, Ma, Cheng, Sorato, Enrico, Johnsson, Martin, Grozou, Christina, Xue, Ying, Liu, Long, Kramer, Guenter, Rubin, Carl-Johan, Cardoso-Moreira, Margarida, McGrew, Mike J., Kaessmann, Henrik

Issue&Volume: 2025-07-16

Abstract: Birds have a sex chromosome system in which females are heterogametic (ZW) and males are homogametic (ZZ)1. The differentiation of avian sex chromosomes from ancestral autosomes entails the loss of most genes from the W chromosome during evolution1,2. However, the extent to which mechanisms evolved that counterbalance this substantial reduction in female gene dosage remains unclear. Here we report functional in vivo and evolutionary analyses of a Z-linked microRNA (miR-2954) with strong male-biased expression, previously proposed to mediate avian sex chromosome dosage compensation3. We knocked out miR-2954 in chicken, which resulted in early embryonic lethality in homozygous knockout males, probably driven by specific upregulation of dosage-sensitive Z-linked target genes. Evolutionary gene expression analyses further revealed that these dosage-sensitive target genes underwent both transcriptional and translational upregulation on the single Z in female birds. Altogether, this work unveils a scenario in which evolutionary pressures following W gene loss drove transcriptional and translational upregulation of dosage-sensitive Z-linked genes in females but also their transcriptional upregulation in males. The resulting excess of transcripts in males, resulting from the combined activity of two upregulated dosage-sensitive Z gene copies, was in turn offset by the emergence of a highly targeted miR-2954-mediated transcript degradation mechanism during avian evolution. This study uncovered a unique sex chromosome dosage compensation system in birds, in which a microRNA has become essential for male survival.

DOI: 10.1038/s41586-025-09256-9

Source: https://www.nature.com/articles/s41586-025-09256-9