论文标题：The mutational landscape of human somatic and germline cells
作者：Moore, Luiza, Cagan, Alex, Coorens, Tim H. H., Neville, Matthew D. C., Sanghvi, Rashesh, Sanders, Mathijs A., Oliver, Thomas R. W., Leongamornlert, Daniel, Ellis, Peter, Noorani, Ayesha, Mitchell, Thomas J., Butler, Timothy M., Hooks, Yvette, Warren, Anne Y., Jorgensen, Mette, Dawson, Kevin J., Menzies, Andrew, O’Neill, Laura, Latimer, Calli, Teng, Mabel, van Boxtel, Ruben, Iacobuzio-Donahue, Christine A., Martincorena, Inigo, Heer, Rakesh, Campbell, Peter J., Fitzgerald, Rebecca C., Stratton, Michael R., Rahbari, Raheleh
期刊：Nature
发表时间：2021/08/25
数字识别码：10.1038/s41586-021-03822-7
摘要：Over the course of an individual’s lifetime, normal human cells accumulate mutations1. Here we compare the mutational landscape in 29 cell types from the soma and germline using multiple samples from the same individuals. Two ubiquitous mutational signatures, SBS1 and SBS5/40, accounted for the majority of acquired mutations in most cell types, but their absolute and relative contributions varied substantially. SBS18, which potentially reflects oxidative damage2, and several additional signatures attributed to exogenous and endogenous exposures contributed mutations to subsets of cell types. The rate of mutation was lowest in spermatogonia, the stem cells from which sperm are generated and from which most genetic variation in the human population is thought to originate. This was due to low rates of ubiquitous mutational processes and may be partially attributable to a low rate of cell division in basal spermatogonia. These results highlight similarities and differences in the maintenance of the germline and soma.
单碱基置换（single base substitution，SBS）突变普遍存在于多种癌组织中。其中，SBS1和SBS5是两种和衰老相关的内源性SBS突变，研究人员发现，被分析的组织中普遍存在这两种突变形式，不过在不同的器官中，这两种形式具有很大的差异。还有两类SBS基因突变是由外界因素导致的，如一名经常吸烟的捐赠者的肝脏中存在较多SBS4突变。与其他组织相比，在胃肠道细胞中存在更多的基因突变。而由于接触到来自身体外部的毒素，肝脏中的细胞也很容易出现基因突变。研究人员还观察到，睾丸中分化成精子的前体细胞具有异常低的基因突变率，仅为体细胞的1/27。他们推测，这些细胞中可能有一些特殊的DNA修复机制，可以保护传递给下一代的遗传物质。
