2026年8月26日，英国桑格研究所Raheleh Rahbari等合作在《自然》发表研究，利用长读长测序技术揭示了精子中存在减数分裂前基因转换事件。

减数分裂重组是一个基本过程，通过创建现有等位基因的新组合来产生遗传多样性。虽然人类中的交叉互换已得到很好的表征，但更为频繁的导致基因转换的非交叉互换事件仍难以研究。在此，研究人员证明，来自精子的单条高保真长读长测序读段可同时捕获交叉互换和非交叉互换事件，从而使得来自单一男性的分析样本量实际上可达到任意大小。他们分析了来自13名供体15份精子样本中的2382个候选非交叉互换事件，并识别出一个具有与PRDM9诱导重组不同特性的稳定组分。这一现象与DMC1结合所确定的减数分裂双链断裂位点、交叉互换重组图谱或GC偏向性基因转换无关，但与基因组脆弱位点相关。这一组分在系谱数据中的父系非交叉互换基因转换中同样存在。将相同分析应用于12份血液样本，研究人员观察到具有相似特性的非交叉互换基因转换，但交叉互换事件极少。此外，他们证明了不同供体之间在不同重组类型上存在差异，即使它们具有相同的PRDM9基因型。研究人员认为，在精子中观察到的大部分非交叉互换基因转换事件可能发生在减数分裂之前。

附：英文原文

Title: Long-read sequencing reveals pre-meiotic gene conversion in sperm

Author: Schweiger, Regev, Lee, Sangjin, Zhou, Chenxi, Yang, Tsun-Po, Li, Stacy, Sanghvi, Rashesh, Neville, Matthew, Smith, Katie, Roberts, Kirsty, Nessa, Ayrun, Wadge, Sam, Small, Kerrin S., Campbell, Peter J., Almstrup, Kristian, Sudmant, Peter H., Rahbari, Raheleh, Durbin, Richard

Issue&Volume: 2026-08-26

Abstract: Meiotic recombination is a fundamental process that generates genetic diversity by creating new combinations of existing alleles. Whereas crossovers in humans are well characterized, the more frequent non-crossovers that lead to gene conversion remain challenging to study. Here we show that single high-fidelity long sequencing reads from sperm can capture both crossovers and non-crossovers, which enables effectively arbitrary sample sizes for analysis from a single male. We analysed 2,382 candidate non-crossovers in 15 sperm samples from 13 donors, and identified a consistent component with properties distinct from PRDM9-induced recombination. This phenomenon was not associated with meiotic double-strand break sites identified by DMC1 binding, the crossover recombination map or GC-biased gene conversion, but was associated with genomic fragile sites. This component is also seen in paternal non-crossover gene conversions in pedigree data. Applying the same analysis to 12 blood samples, we observed non-crossover gene conversions with similar properties, but very few crossover events. Further, we demonstrate variation between donors for the different types of recombination, even when they share the same PRDM9 genotype. We suggest that a substantial fraction of the non-crossover gene conversion events seen in sperm arise prior to meiosis.

DOI: 10.1038/s41586-026-10901-0

Source: https://www.nature.com/articles/s41586-026-10901-0