Genome-wide methylation in the panmictic European eel (Anguilla anguilla)

The role of methylation in adaptive, developmental and speciation processes has attracted considerable interest, but interpretation of results is complicated by diffuse boundaries between genetic and non-genetic variation. We studied whole genome genetic and methylation variation in the European eel, distributed from subarctic to subtropical environments, but with panmixia precluding genetically based local adaptation beyond single-generation responses. Overall methylation was 70.9%, with hypomethylation predominantly found in promoters and first exons. Redundancy analyses involving juvenile glass eels showed 0.06% and 0.03% of the variance at SNPs to be explained by localities and environmental variables, respectively, with GO terms of genes associated with outliers primarily involving neural system functioning. For CpGs 2.98% and 1.36% of variance was explained by localities and environmental variables. Differentially methylated regions particularly included genes involved in developmental processes, with hox clusters featuring prominently. Life stage (adult versus glass eels) was the most important source of inter-individual variation in methylation, likely reflecting both ageing and developmental processes. Demethylation of transposable elements relative to pure European eel was observed in European X American eel hybrids, possibly representing postzygotic barriers in this system characterized by prolonged speciation and ongoing gene flow. Whereas the genetic data are consistent with a role of single-generation selective responses, the methylation results underpin the importance of epigenetics in the life cycle of eels and suggests interactions between local environments, development and phenotypic variation mediated by methylation variation. Eels are remarkable by having retained eight hox clusters, and the results suggest important roles of methylation at hox genes for adaptive processes.

甲基化在适应性、发育以及物种形成过程中的作用已引起广泛关注，但由于遗传变异与非遗传变异之间的界限模糊，对研究结果的解读变得复杂。我们对分布于亚北极至亚热带环境中的欧洲鳗鲡进行了全基因组遗传变异与甲基化变异分析，该物种因存在随机泛交（panmixia）现象，故而无法产生超越单代响应的遗传型局部适应性。整体甲基化水平为70.9%，低甲基化主要出现在启动子和第一外显子区域。针对幼体玻璃鳗的冗余分析结果显示，单核苷酸多态性（Single Nucleotide Polymorphisms，SNPs）位点的变异中，分别有0.06%和0.03%可由采样地点与环境变量解释；与变异异常位点相关的基因所对应的基因本体（Gene Ontology，GO）术语主要涉及神经系统功能。对于CpG位点，其变异分别有2.98%和1.36%可由采样地点和环境变量解释。差异甲基化区域尤其涵盖了与发育过程相关的基因，其中hox簇表现尤为突出。生命阶段（成体与玻璃鳗）是个体间甲基化变异的最主要来源，这可能同时反映了衰老与发育双重过程的影响。相较于纯种欧洲鳗鲡，欧洲与美洲鳗鲡的杂交个体中出现了转座元件的去甲基化现象，这可能代表了该系统中存在的合子后生殖隔离——该系统以长期的物种形成过程与持续的基因流为典型特征。尽管遗传数据与单代选择性响应的作用相符，但甲基化研究结果证实了表观遗传学（epigenetics）在鳗鲡生命周期中的重要性，并揭示了局部环境、发育过程与甲基化变异介导的表型变异之间存在相互作用。鳗鲡的显著特征之一是保留了8个hox簇，本研究结果表明，hox基因的甲基化在适应性过程中发挥着关键作用。