DNA damage repair (DDR) system is vital in maintaining genome stability and survival. DDR consists of over 160 genes in 7 different pathways to repair specific type of DNA damage caused by external and internal damaging factors. The functional importance of DDR system implies that evolution could play important roles in maintaining its functional intactness to perform its function. Indeed, it has been observed that positive selection is present in BRCA1 and BRCA2 (BRCA), which are key genes in homologous recombination pathway of DDR system, in the humans and its close relatives of chimpanzee and bonobos. Efforts have been made to investigate whether the same selection could exist for BRCA in other mammals but found no evidence so far. However, as most of the studies in non-human mammals analyzed only a single or few individuals in the studied species, the observation may not reflect the true status in the given species. Furthermore, few studies have studied evolution selection in other DDR genes except BRCA. In current study, we used laboratory mouse C57BL/6 J as a model to address evolution selection on DDR genes in non-primate mammals by dynamically monitoring genetic variation across 30 generations in C57BL/6 J. Using exome sequencing, we collected coding sequences of 169 DDR genes from 44 C57BL/6 J individual genomes in 2018. We compared the coding sequences with the mouse reference genome sequences derived from 1998 C57BL/6 J DNA, and with the mouse Eve6B reference genome sequences derived from 2003 C57BL/6 J DNA, covering 30 generations of C57BL/6 J from 1998 to 2018. We didn’t identify meaningful coding variation in either Brca1 or Brca2, or in 167 other DDR genes across the 30 generations. In the meantime, we did identify 812 coding variants in 116 non-DNA damage repair genes during the same period, which served as a quality control to validate the reliability of our analytic pipeline and the negative results in DDR genes. DDR genes in laboratory mouse strain C57BL/6 J were not under positive selection across its 30-generation period, highlighting the possibility that DDR system in rodents could be evolutionarily stable.

中文翻译：

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C57BL/6 J 小鼠 DNA 损伤修复系统进化稳定

DNA 损伤修复 (DDR) 系统对于维持基因组稳定性和存活至关重要。DDR 由 7 种不同途径的 160 多个基因组成，用于修复由外部和内部损伤因素引起的特定类型的 DNA 损伤。DDR 系统的功能重要性意味着进化可以在维持其功能完整性以执行其功能方面发挥重要作用。事实上，已经观察到正选择存在于人类及其近亲黑猩猩和倭黑猩猩的 DDR 系统同源重组途径中的关键基因 BRCA1 和 BRCA2 (BRCA) 中。已经努力调查在其他哺乳动物中是否存在相同的 BRCA 选择，但迄今为止没有发现任何证据。然而，由于大多数非人类哺乳动物的研究仅分析了研究物种中的单个或少数个体，因此观察结果可能无法反映特定物种的真实状况。此外，很少有研究研究除 BRCA 之外的其他 DDR 基因的进化选择。在当前的研究中，我们使用实验室小鼠 C57BL/6 J 作为模型，通过动态监测 C57BL/6 J 中 30 代的遗传变异来解决非灵长类哺乳动物中 DDR 基因的进化选择。使用外显子组测序，我们收集了2018 年来自 44 个 C57BL/6 J 个体基因组的 169 个 DDR 基因。我们将编码序列与来自 1998 C57BL/6 J DNA 的小鼠参考基因组序列以及来自 2003 C57BL/6 J DNA 的小鼠 Eve6B 参考基因组序列进行了比较，涵盖1998年至2018年30代C57BL/6 J。我们没有在 Brca1 或 Brca2 或 30 代的 167 个其他 DDR 基因中发现有意义的编码变异。与此同时，我们确实在同一时期在 116 个非 DNA 损伤修复基因中鉴定了 812 个编码变异，作为质量控制来验证我们分析管道的可靠性和 DDR 基因的阴性结果。实验室小鼠品系 C57BL/6 J 中的 DDR 基因在其 30 代期间未处于正选择状态，这突显了啮齿类动物的 DDR 系统在进化上可能稳定的可能性。它作为质量控制来验证我们分析流程的可靠性和 DDR 基因的阴性结果。实验室小鼠品系 C57BL/6 J 中的 DDR 基因在其 30 代期间未处于正选择状态，这突显了啮齿类动物的 DDR 系统在进化上可能稳定的可能性。它作为质量控制来验证我们分析流程的可靠性和 DDR 基因的阴性结果。实验室小鼠品系 C57BL/6 J 中的 DDR 基因在其 30 代期间未处于正选择状态，这突显了啮齿类动物的 DDR 系统在进化上可能稳定的可能性。