Epigenetic potential: Promoter CpG content positively covaries with lifespan and is dependent on gene function among vertebrates
Epigenetic potential: Promoter CpG content positively covaries with lifespan and is dependent on gene function among vertebrates
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表观遗传潜力：启动子 CpG 含量与寿命呈正相关，并且取决于脊椎动物的基因功能
DOI：
10.1093/jhered/esad006
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发表时间：
2023
影响因子：
3.1
通讯作者：
vonHoldt, ed., Bridgett
中科院分区：
文献类型：
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作者：
Sheldon, Elizabeth L.;Schrey, Aaron W.;Lauer, M. Ellesse;Martin, Lynn B.;vonHoldt, ed., Bridgett
DNA甲基化的变异与许多生态和生活史特征有关，包括生态位宽度和寿命。在脊椎动物中，DNA甲基化几乎只发生在“CpG”二核苷酸上。然而，基因组CpG含量的变化如何影响生物生态在很大程度上被忽视了。在这里，我们探索了60种羊膜脊椎动物中启动子CpG含量、寿命和生态位宽度之间的关系。在哺乳动物和爬行动物中，16个功能相关基因启动子的CpG含量与寿命呈显著正相关，而与生态位宽度无关。可能，通过为CpG甲基化提供更多底物，高启动子CpG含量延长了CpG甲基化模式中有害的、与年龄相关的错误积累所需的时间，从而延长了寿命。CpG含量和寿命之间的关联是由具有中间CpG丰度的基因启动子驱动的-那些已知易于通过甲基化进行调节的基因启动子。我们的发现为这种观点提供了新的支持，即在长寿物种中选择高CpG含量是为了保持通过CpG甲基化来调节基因表达的能力。有趣的是，在我们的研究中，启动子CpG的含量也依赖于基因功能；免疫基因的CpG位点比代谢和应激相关基因平均少20%。
Variation in DNA methylation is associated with many ecological and life history traits, including niche breadth and lifespan. In vertebrates, DNA methylation occurs almost exclusively at “CpG” dinucleotides. Yet, how variation in the CpG content of the genome impacts organismal ecology has been largely overlooked. Here, we explore associations between promoter CpG content, lifespan and niche breadth among 60, amniote vertebrate species. The CpG content of 16 functionally relevant gene promoters was strongly, positively associated with lifespan in mammals and reptiles, but was not related to niche breadth. Possibly, by providing more substrate for CpG methylation to occur, high promoter CpG content extends the time taken for deleterious, age-related errors in CpG methylation patterns to accumulate, thereby extending lifespan. The association between CpG content and lifespan was driven by gene promoters with intermediate CpG enrichment—those known to be predisposed to regulation by methylation. Our findings provide novel support for the idea that high CpG content has been selected for in long-lived species to preserve the capacity for gene expression regulation by CpG methylation. Intriguingly, promoter CpG content was also dependent on gene function in our study; immune genes had on average 20% less CpG sites than metabolic- and stress-related genes.