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Abstract There is a growing focus on the role of DNA methylation in the ability of marine invertebrates to rapidly respond to changing environmental factors and anthropogenic impacts. However, genome‐wide DNA methylation studies in nonmodel organisms are currently hampered by a limited understanding of methodological biases. Here, we compare three methods for quantifying DNA methylation at single base‐pair resolution—whole genome bisulfite sequencing (WGBS), reduced representation bisulfite sequencing (RRBS), and methyl‐CpG binding domain bisulfite sequencing (MBDBS)—using multiple individuals from two reef‐building coral species with contrasting environmental sensitivity. All methods reveal substantially greater methylation inMontipora capitata(11.4%) than the more sensitivePocillopora acuta(2.9%). The majority of CpG methylation in both species occurs in gene bodies and flanking regions. In both species, MBDBS has the greatest capacity for detecting CpGs in coding regions at our sequencing depth, but MBDBS may be influenced by intrasample methylation heterogeneity. RRBS yields robust information for specific loci albeit without enrichment of any particular genome feature and with significantly reduced genome coverage. Relative genome size strongly influences the number and location of CpGs detected by each method when sequencing depth is limited, illuminating nuances in cross‐species comparisons. As genome‐wide methylation differences, supported by data across bisulfite sequencing methods, may contribute to environmental sensitivity phenotypes in critical marine invertebrate taxa, these data provide a genomic resource for investigating the functional role of DNA methylation in environmental tolerance. 

ABSTRACT As climate change increases the rate of environmental change and the frequency and intensity of disturbance events, selective forces intensify. However, given the complicated interplay between plasticity and selection for ecological – and thus evolutionary – outcomes, understanding the proximate signals, molecular mechanisms and the role of environmental history becomes increasingly critical for eco-evolutionary forecasting. To enhance the accuracy of our forecasting, we must characterize environmental signals at a level of resolution that is relevant to the organism, such as the microhabitat it inhabits and its intracellular conditions, while also quantifying the biological responses to these signals in the appropriate cells and tissues. In this Commentary, we provide historical context to some of the long-standing challenges in global change biology that constrain our capacity for eco-evolutionary forecasting using reef-building corals as a focal model. We then describe examples of mismatches between the scales of external signals relative to the sensors and signal transduction cascades that initiate and maintain cellular responses. Studying cellular responses at this scale is crucial because these responses are the basis of acclimation to changing environmental conditions and the potential for environmental ‘memory’ of prior or historical conditions through molecular mechanisms. To challenge the field, we outline some unresolved questions and suggest approaches to align experimental work with an organism's perception of the environment; these aspects are discussed with respect to human interventions.