Sex and social status influence DNA methylation dynamics in a polygynous bat. Sex and social status influence DNA methylation dynamics in a polygynous bat

DNA methylation (DNAm) influences when and where genes are expressed or repressed during growth and development. Recently, patterns of DNAm at conserved genomic sites have been discovered that predict chronological age in all mammals. Deviations from these ‘epigenetic clocks’ have been used to identify factors that alter the aging process. In this study, we profile DNAm with a custom microarray for over 330 wild Phyllostomus hastatus, a highly polygynous bat in which unrelated females form long-lasting associations and larger males compete aggressively to control mating access to female groups. DNAm age estimates reveal that females can live more than 1.5 times as long as males. After fitting linear models for age, sex and their interaction we find that DNAm changes 1.4 times faster in males than females at thousands of sites. Therefore, even though age of either sex can be predicted by a common set of sites, the methylome of males is more dynamic than that of females. Sites associated with differences in the rate of change between males and females are sensitive to androgens and enriched on the X chromosome. Those that gain methylation with age in both sexes are associated with active and repressive chromatin states in blood and are enriched in promoters of genes involved in regulation of metabolic processes. In contrast, few sites differ in DNAm rate between males of different reproductive status, though subordinate males exhibit faster DNAm change than dominant males. Thus, males have accelerated physiological processes in comparison to females that likely increase mating success but reduce survival. Overall design: We aimed to identify sex and age-associated methylation sites using DNA extracted from skin samples of wild-caught greater spear-nosed bats, Phyllostomus hastatus. We used the HorvathMammalMethylChip40, and estimated ages using existing methylation clocks from Wilkinson et al. 2021 (PMC7955057)

DNA甲基化（DNA methylation）可调控基因在生长发育过程中的表达与沉默的时机与位置。近年来，研究者在保守基因组位点中发现了DNA甲基化模式，可用于预测所有哺乳动物的实际年龄。针对这些“表观遗传时钟（epigenetic clocks）”的偏差分析，已被用于识别可改变衰老进程的相关因素。
本研究利用定制微阵列对超过330只野生大矛吻蝠（Phyllostomus hastatus）的DNA甲基化水平进行谱分析。该物种为高度一夫多妻制的蝙蝠，无亲缘关系的雌性个体可形成长期社群，体型更大的雄性则会通过激烈竞争掌控与雌性群体的交配权限。
DNA甲基化年龄估算结果显示，雌性的寿命可达雄性的1.5倍以上。在针对年龄、性别及其交互作用构建线性模型后，我们发现数千个位点的DNA甲基化变化速率在雄性中是雌性的1.4倍。因此，尽管通过一组共有的位点即可预测不同性别的个体年龄，但雄性的甲基化组（methylome）比雌性更为动态。
与雌雄甲基化变化速率差异相关的位点对雄激素敏感，且在X染色体上富集。在两种性别中均随年龄增长而发生甲基化水平升高的位点，与血液中活跃及沉默的染色质状态相关，并富集于参与代谢过程调控的基因启动子区域。与之相反，不同繁殖状态的雄性之间，其DNA甲基化速率的差异位点极少，不过从属雄性的DNA甲基化变化速率要快于优势雄性。由此可见，相较于雌性，雄性的生理进程更快，这或可提升交配成功率，但会降低存活概率。
总体实验设计：本研究旨在通过提取野生捕获的大矛吻蝠皮肤样本中的DNA，识别与性别和年龄相关的甲基化位点。我们使用了HorvathMammalMethylChip40芯片，并基于Wilkinson等人2021年发表的研究（PMC7955057）中的现有甲基化时钟模型估算个体年龄。