Anderson Jordan A, Lin Dana, Lea Amanda J, Johnston Rachel A, Voyles Tawni, Akinyi Mercy Y, Archie Elizabeth A, Alberts Susan C, Tung Jenny
Department of Evolutionary Anthropology, Duke University, Durham, North Carolina 27708, USA.
Canadian Institute for Advanced Research, Toronto, Canada M5G 1M1, Canada.
bioRxiv. 2023 Jun 5:2023.06.05.542485. doi: 10.1101/2023.06.05.542485.
The early life environment can profoundly shape the trajectory of an animal's life, even years or decades later. One mechanism proposed to contribute to these early life effects is DNA methylation. However, the frequency and functional importance of DNA methylation in shaping early life effects on adult outcomes is poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation estimates at 477,270 CpG sites in 256 wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood: aspects of the environment linked to resource limitation (e.g., low-quality habitat, early life drought) are associated with many more CpG sites than other types of environmental stressors (e.g., low maternal social status). Sites associated with early resource limitation are enriched in gene bodies and putative enhancers, suggesting they are functionally relevant. Indeed, by deploying a baboon-specific, massively parallel reporter assay, we show that a subset of windows containing these sites are capable of regulatory activity, and that, for 88% of early drought-associated sites in these regulatory windows, enhancer activity is DNA methylation-dependent. Together, our results support the idea that DNA methylation patterns contain a persistent signature of the early life environment. However, they also indicate that not all environmental exposures leave an equivalent mark and suggest that socioenvironmental variation at the time of sampling is more likely to be functionally important. Thus, multiple mechanisms must converge to explain early life effects on fitness-related traits.
早期生活环境能够深刻地塑造动物的生命轨迹，甚至在数年或数十年之后依然如此。一种被认为对这些早期生活影响有作用的机制是DNA甲基化。然而，DNA甲基化在塑造早期生活对成年后结果的影响方面的频率和功能重要性却鲜为人知，尤其是在自然种群中。在此，我们将前瞻性收集的关于早期环境中与适应性相关变异的数据，与256只野生狒狒中477,270个CpG位点的DNA甲基化估计值进行整合。我们发现，成年期的早期生活环境与DNA甲基化之间存在高度异质性的关系：与资源限制相关的环境因素（例如，低质量栖息地、早期生活干旱）比其他类型的环境应激源（例如，低母体社会地位）与更多的CpG位点相关。与早期资源限制相关的位点在基因体和假定的增强子中富集，表明它们在功能上具有相关性。事实上，通过部署一种狒狒特异性的大规模平行报告基因检测，我们表明包含这些位点的一部分窗口具有调控活性，并且对于这些调控窗口中88%的与早期干旱相关的位点，增强子活性是DNA甲基化依赖性的。总之，我们的结果支持了DNA甲基化模式包含早期生活环境的持久特征这一观点。然而，它们也表明并非所有的环境暴露都会留下同等的印记，并表明采样时的社会环境变异更有可能在功能上具有重要意义。因此，必须有多种机制共同作用来解释早期生活对与适应性相关性状的影响。
