染色体稳定性是基因组进化的关键点，尤其是Y染色体的进化。已经确立了血液和肿瘤细胞中Y染色体的丢失。通过与其他染色体相同的过程，Y染色体在血液中进行退化和断裂，然后被排出。这个过程产生了循环DNA（cirDNA）片段，对血液中的DNA断裂在Y染色体的消失中起到了潜在洞察的作用。在这项研究中，我们采用了浅部分基因组测序（sWGS）来全面评估健康男性个体的血浆中的总循环DNA和个别染色体片段的大小分布。我们在这里展示了以下结果：（i）血浆中的总循环DNA（cirDNA）和源于其它常染色体和X染色体的DNA片段的大小分布是均匀的，健康个体间具有显著低的变异性（平均CV = 7%）；（ii）Y染色体具有明显不同的片段大小分布，其片段长度小于145 bp的富集，二核苷体相关片段的消耗（290-390 bp），并且随着年龄增长，其在血液中的片段比例逐渐减少。这些结果表明与其他染色体相比，Y染色体具有更高的断裂，这可能是由于其更容易退化的原因。我们的发现为阐明染色体来源对DNA退化和Y染色体生物学的影响铺平了道路。© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.

Chromosome stability is a key point in genome evolution, particularly that of the Y chromosome. The Y chromosome loss in blood and tumor cells is well established. Through processes that are common to other chromosomes too, the Y chromosome undergoes degradation and fragmentation in the blood stream before elimination. This process gives rise to circulating DNA (cirDNA) fragments, whose examination may provide potential insight into the role of DNA fragmentation in blood for the Y chromosome elimination. In this study, we employed shallow whole genome sequencing (sWGS) to comprehensively assess the total cirDNA and the individual chromosome fragment size profiles in the plasma of healthy male individuals. Here, we show that (i) the fragment size profiles of total circulating DNA (cirDNA) and DNA fragments originating from autosomes and the X chromosome in blood plasma are homogeneous, and have a remarkably low variability (mean CV = 7%) among healthy individuals, (ii) the Y chromosome has a distinct fragment size profile with the accumulation of the fragment < 145 bp and depletion of the dinucleosome-associated fragments (290-390 bp), and its fragment fraction in blood decreases with age. These results indicate a higher fragmentation of the Y chromosome compared to other chromosomes and this in turn might be due to its increased susceptibility to degradation. Our findings pave the way for an elucidation of the impact of chromosomal origin on DNA degradation and the Y chromosome biology.© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.