Dumont Beth L, Handel Mary Ann
The Jackson Laboratory, Bar Harbor, ME, USA.
Curr Opin Genet Dev. 2025 Aug;93:102365. doi: 10.1016/j.gde.2025.102365. Epub 2025 May 23.
A hallmark of meiosis is pairing of homologous chromosomes, an event that ensures proper segregation into the gametes. Homology pairing is crucial to the formation of normal gametes, the maintenance of genomic integrity, and avoidance of aneuploidy. However, chromosomes are not completely homologous. Here we discuss two notable exceptions to homology: the mammalian sex chromosomes and centromeres. In themselves, these exceptions illustrate meiotic adaptations that both ensure correct chromosome segregation and present evolutionary opportunities. More broadly, such examples of non-homology provide a window for viewing normal mechanisms of meiotic pairing and chromosome modifications. Current analyses of mammalian meiotic chromosome dynamics suggest that the basis for the initial recognition of homology early in meiosis may be based in epigenetic chromatin modifications. Chromatin units may both form pairing sites and provide the modifications that allow non-homologous sequences to be tolerated. Despite recent research progress, we have yet to understand why some non-homologies are tolerated, while others lead to aneuploidy. Understanding how genomes evolve strategies to subvert the usual rules of meiosis will benefit from studies focused on the identification and characterization of meiosis in species with recently acquired non-homology. Looking forward, we are now armed with technologies and tools suited to precisely measure the extent of nonhomology across mammalian chromosomes and to probe the molecular and biophysical steps required for the initiation of homologous chromosome recognition and pairing. These goals are important for elucidating an essential mechanism of meiosis and ultimately for advancing the clinical diagnosis of gametic and embryo aneuploidy.
减数分裂的一个标志是同源染色体配对，这一事件可确保染色体正确分离到配子中。同源性配对对于正常配子的形成、基因组完整性的维持以及避免非整倍体至关重要。然而，染色体并非完全同源。在此，我们讨论同源性的两个显著例外：哺乳动物的性染色体和着丝粒。就其本身而言，这些例外说明了减数分裂的适应性变化，既能确保正确的染色体分离，又能提供进化机会。更广泛地说，这种非同源性的例子为观察减数分裂配对和染色体修饰的正常机制提供了一个窗口。目前对哺乳动物减数分裂染色体动态的分析表明，减数分裂早期同源性初始识别的基础可能基于表观遗传染色质修饰。染色质单元既可以形成配对位点，也可以提供允许非同源序列被容忍的修饰。尽管最近有研究进展，但我们仍不清楚为什么一些非同源性能够被容忍，而另一些却会导致非整倍体。了解基因组如何进化出策略来颠覆减数分裂的常规规则，将受益于专注于鉴定和表征具有最近获得的非同源性物种减数分裂的研究。展望未来，我们现在拥有了适合精确测量哺乳动物染色体上非同源程度以及探究同源染色体识别和配对起始所需分子和生物物理步骤的技术和工具。这些目标对于阐明减数分裂的基本机制至关重要，最终对于推进配子和胚胎非整倍体的临床诊断也很重要。
