Document Type
Article
Publication Date
5-22-2025
Original Citation
Dumont B,
Handel M.
Non-homologous sequence interactions during meiosis: meiotic challenges and evolutionary opportunities. Curr Opin Genet Dev. 2025;93:102365.
Keywords
JGM
JAX Source
Curr Opin Genet Dev. 2025;93:102365.
ISSN
1879-0380
PMID
40409127
DOI
https://doi.org/10.1016/j.gde.2025.102365
Grant
Preparation of this review was funded in part by a Maximizing Investigators’ Research Award from the National Institute of General Medical Sciences to BLD (R35 GM133415).
Abstract
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.
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