MEIOSIN retains a STRA8-independent activity that contributes to meiotic gene activation across vertebrates.

Meiotic entry in vertebrates has been viewed as a transcriptional switch driven by the MEIOSIN-STRA8 axis, but whether this represents the ancestral regulatory logic of meiosis has remained unclear. Here we combine comparative genomics with genetic and single-cell analyses in zebrafish and mice to show that MEIOSIN retains an intrinsic STRA8-independent activity. We identify Meiosin orthologs in zebrafish and hagfish, vertebrate lineages that lack Stra8, and show that these proteins retain the HMG domain but have lost the bHLH domain required for the canonical MEIOSIN-STRA8 interaction. In zebrafish, meiosin is transiently induced at meiotic entry in both sexes, yet its loss selectively disrupts the female germline, causing failure of oogenesis and female-to-male sex reversal. In mice, MEIOSIN lacking the bHLH domain still initiates key features of meiotic entry and partially activates meiotic target genes, although it fails to support full meiotic progression. Together, these findings support a model in which HMG-containing MEIOSIN provides a conserved core activity for meiotic gene activation, whereas STRA8 and the bHLH-mediated MEIOSIN-STRA8 interaction reinforce the efficiency and robustness of this program in lineages that retain the canonical module.