Harper Jon A, Brown George G B, Neale Matthew J
Genome Damage and Stability Centre, School of Life Sciences, University of Sussex, Brighton, U.K.
Biochem Soc Trans. 2025 Apr 2;53(2):BST20253019. doi: 10.1042/BST20253019.
Meiotic recombination is required to break up gene linkage and facilitate faithful chromosome segregation during gamete formation. By inducing DNA double-strand breaks, Spo11, a protein that is conserved in all meiotic organisms, initiates the process of recombination. Here, we chart the evolutionary history of Spo11 and compare the protein to its ancestors. Evolving from the A subunit of archaeal topoisomerase VI (Topo VI), a heterotetrameric type II topoisomerase, Spo11 appears to have evolved alongside meiosis and been present in the last eukaryotic common ancestor. There are many differences between Spo11 and TopVIA, particularly in regulation, despite similarities in structure and mechanism of action. Critical to its function as an inducer of recombination, Spo11 has an apparently amputated activity that, unlike topoisomerases, does not re-seal the DNA breaks it creates. We discuss how and why Spo11 has taken its path down the tree of life, considering its regulation and its roles compared with those of its progenitor Topo VI, in both meiotic and non-meiotic species. We find some commonality between different forms and orthologs of Spo11 in different species and touch upon how recent biochemical advances are beginning to finally unlock the molecular secrets hidden within this fundamental yet enigmatic protein.
减数分裂重组对于打破基因连锁和促进配子形成过程中染色体的准确分离是必需的。通过诱导DNA双链断裂,Spo11(一种在所有减数分裂生物体中都保守的蛋白质)启动了重组过程。在这里,我们梳理了Spo11的进化历史,并将该蛋白质与其祖先进行了比较。Spo11由古细菌拓扑异构酶VI(Topo VI)的A亚基进化而来,Topo VI是一种异源四聚体II型拓扑异构酶,它似乎与减数分裂一同进化,并存在于最后的真核生物共同祖先中。尽管Spo11与TopVIA在结构和作用机制上有相似之处,但两者之间存在许多差异,特别是在调控方面。对于其作为重组诱导剂的功能至关重要的是,Spo11具有一种明显被截断的活性,与拓扑异构酶不同,它不会重新封闭其产生的DNA断裂。我们讨论了Spo11在生命之树上是如何以及为何走上这条道路的,同时考虑了其调控以及与它的祖先Topo VI相比,在减数分裂和非减数分裂物种中的作用。我们发现不同物种中Spo11的不同形式和直系同源物之间存在一些共性,并探讨了最近的生化进展如何最终开始揭示隐藏在这种基本但神秘的蛋白质中的分子秘密。