小柯机器人

美国田纳西大学GarrisonView小组发现异源人类近端着丝粒染色体之间的重组。相关论文于2023年5月10日发表于国际学术期刊《自然》。

研究人员表示，人类近端着丝粒染色体（SAAC）的短臂共享大量的同源区域，包括核糖体DNA重复和扩展的片段重复。尽管在人类基因组的第一个完整组装T2T-CHM13（the Telomere-to-Telomere Consortium’s CHM13 assembly）中对这些区域的解析提供了一个同源性的模型，但仍不清楚这些模式是祖先的还是通过持续的重组交换来维持的。

研究人员表明，近端着丝粒染色体含有假同源区（PHR），表明非同源序列之间的重组。利用HPRC（Human Pangenome Reference Consortium）对人类泛基因组的比较，研究人员发现来自所有SAAC的等位基因形成了一个共同体。由横跨中心点的同位素片段构建的变异图谱表明，在T2T-CHM13的近端着丝粒染色体之间存在着大多数片段几乎相同的区域。除15号染色体外，研究人员观察到假同源区的连锁不平衡衰减速度比相应的短臂和长臂快，表明重组率较高。假同源区包括以前被证明位于罗伯逊易位断点处的序列，它们的排列与13、14和21号染色体上倒置复制的交叉相一致。在HPRC草图中看到的异源近端着丝粒染色体之间重组信号的普遍性表明，这些共享序列构成了复发性罗伯逊易位的基础，为50年前从细胞遗传学研究中首次提出的假说提供了序列和基于种群的确认。

附：英文原文

Title: Recombination between heterologous human acrocentric chromosomes

Author: Guarracino, Andrea, Buonaiuto, Silvia, de Lima, Leonardo Gomes, Potapova, Tamara, Rhie, Arang, Koren, Sergey, Rubinstein, Boris, Fischer, Christian, Gerton, Jennifer L., Phillippy, Adam M., Colonna, Vincenza, Garrison, Erik

Issue&Volume: 2023-05-10

Abstract: The short arms of the human acrocentric chromosomes 13, 14, 15, 21 and 22 (SAACs) share large homologous regions, including ribosomal DNA repeats and extended segmental duplications1,2. Although the resolution of these regions in the first complete assembly of a human genome—the Telomere-to-Telomere Consortium’s CHM13 assembly (T2T-CHM13)—provided a model of their homology3, it remained unclear whether these patterns were ancestral or maintained by ongoing recombination exchange. Here we show that acrocentric chromosomes contain pseudo-homologous regions (PHRs) indicative of recombination between non-homologous sequences. Utilizing an all-to-all comparison of the human pangenome from the Human Pangenome Reference Consortium4 (HPRC), we find that contigs from all of the SAACs form a community. A variation graph5 constructed from centromere-spanning acrocentric contigs indicates the presence of regions in which most contigs appear nearly identical between heterologous acrocentric chromosomes in T2T-CHM13. Except on chromosome 15, we observe faster decay of linkage disequilibrium in the pseudo-homologous regions than in the corresponding short and long arms, indicating higher rates of recombination6,7. The pseudo-homologous regions include sequences that have previously been shown to lie at the breakpoint of Robertsonian translocations8, and their arrangement is compatible with crossover in inverted duplications on chromosomes 13, 14 and 21. The ubiquity of signals of recombination between heterologous acrocentric chromosomes seen in the HPRC draft pangenome suggests that these shared sequences form the basis for recurrent Robertsonian translocations, providing sequence and population-based confirmation of hypotheses first developed from cytogenetic studies 50 years ago9.

DOI: 10.1038/s41586-023-05976-y

Source: https://www.nature.com/articles/s41586-023-05976-y

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html