Raynaud Marie, Sanna Paola, Joseph Julien, Clément Julie, Imai Yukiko, Lareyre Jean-Jacques, Laurent Audrey, Galtier Nicolas, Baudat Frédéric, Duret Laurent, Gagnaire Pierre-Alexandre, de Massy Bernard
ISEM, Univ Montpellier, CNRS, IRD, Montpellier, France.
Institut de Génétique Humaine, Univ Montpellier, Centre National de la Recherche Scientifique, Montpellier, France.
PLoS Biol. 2025 Jan 6;23(1):e3002950. doi: 10.1371/journal.pbio.3002950. eCollection 2025 Jan.
In many eukaryotes, meiotic recombination occurs preferentially at discrete sites, called recombination hotspots. In various lineages, recombination hotspots are located in regions with promoter-like features and are evolutionarily stable. Conversely, in some mammals, hotspots are driven by PRDM9 that targets recombination away from promoters. Paradoxically, PRDM9 induces the self-destruction of its targets and this triggers an ultra-fast evolution of mammalian hotspots. PRDM9 is ancestral to all animals, suggesting a critical importance for the meiotic program, but has been lost in many lineages with surprisingly little effect on meiosis success. However, it is unclear whether the function of PRDM9 described in mammals is shared by other species. To investigate this, we analyzed the recombination landscape of several salmonids, the genome of which harbors one full-length PRDM9 and several truncated paralogs. We identified recombination initiation sites in Oncorhynchus mykiss by mapping meiotic DNA double-strand breaks (DSBs). We found that DSBs clustered at hotspots positioned away from promoters, enriched for the H3K4me3 and H3K36me3 and the location of which depended on the genotype of full-length Prdm9. We observed a high level of polymorphism in the zinc finger domain of full-length Prdm9, indicating diversification driven by positive selection. Moreover, population-scaled recombination maps in O. mykiss, Oncorhynchus kisutch and Salmo salar revealed a rapid turnover of recombination hotspots caused by PRDM9 target motif erosion. Our results imply that PRDM9 function is conserved across vertebrates and that the peculiar evolutionary runaway caused by PRDM9 has been active for several hundred million years.
在许多真核生物中，减数分裂重组优先发生在离散位点，即所谓的重组热点。在不同的谱系中，重组热点位于具有启动子样特征的区域，并且在进化上是稳定的。相反，在一些哺乳动物中，热点是由PRDM9驱动的，它将重组靶向远离启动子的区域。矛盾的是，PRDM9会诱导其靶点的自我毁灭，这引发了哺乳动物热点的超快速进化。PRDM9是所有动物的祖先基因，这表明它对减数分裂程序至关重要，但在许多谱系中已经丢失，对减数分裂的成功却几乎没有影响。然而，尚不清楚哺乳动物中描述的PRDM9功能是否为其他物种所共有。为了研究这一点，我们分析了几种鲑科鱼类的重组图谱，其基因组包含一个全长PRDM9和几个截短的旁系同源基因。我们通过绘制减数分裂DNA双链断裂（DSB）图谱，在虹鳟中确定了重组起始位点。我们发现DSB聚集在远离启动子的热点区域，这些区域富含H3K4me3和H3K36me3，其位置取决于全长Prdm9的基因型。我们观察到全长Prdm9的锌指结构域存在高度多态性，表明是由正选择驱动的多样化。此外，虹鳟、银大麻哈鱼和大西洋鲑的群体规模重组图谱显示，由于PRDM9靶基序的侵蚀，重组热点快速更替。我们的结果表明，PRDM9的功能在脊椎动物中是保守的，并且由PRDM9引起的特殊进化失控已经活跃了数亿年。
