SRA

The early life environment can profoundly shape the trajectory of life course, even years or decades later in life. DNA methylation is often proposed as a contributing mechanism that links early life experience to later life outcomes. However, the frequency and functional importance of links between early life experience and DNA methylation patterns in adulthood are poorly understood, especially in natural populations. Here, we integrate prospectively collected data on fitness-associated variation in the early environment with DNA methylation in adult wild baboons. We find highly heterogeneous relationships between the early life environment and DNA methylation in adulthood, such that aspects of the environment directly linked to resource limitation are associated with orders of magnitude more sites than other types of environmental stressors. Early resource limitation-associated sites are enriched in gene bodies and putative enhancers, suggesting their functional relevance. Indeed, by deploying a baboon-specific massively parallel reporter assay, we show that windows containing these sites are more likely to exhibit enhancer-like activity than expected by chance, and that, in majority of these cases, the magnitude of enhancer activity depends on DNA methylation. 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 types of environmental exposures leave an equivalent mark, indicating that multiple mechanisms must converge to explain early life effects on fertility and survival.