ABSTRACT

Epigenetic modifications can contribute to adaptation, but the relative contributions of genetic and epigenetic variation are unknown. Previous studies on the role of epigenetic changes in adaptation in eukaryotes have nearly exclusively focused on cytosine methylation (m5C), while prokaryotes exhibit a richer system of methyltransferases targetting adenines (m6A) or cytosines (m4C, m5C). DNA methylation in prokaryotes has many roles, but its potential role in adaptation still needs further investigation. We collected phenotypic, genetic, and epigenetic data using single molecule real-time sequencing of clones of the bacterium Serratia marcescens that had undergone experimental evolution in contrasting temperatures to investigate the relationship between environment and genetic, epigenetic, and phenotypic changes. The genomic distribution of GATC motifs, which were the main target for m6A methylation, and of variable m6A epiloci pointed to a potential link between m6A methylation and regulation of gene expression in S. marcescens. Evolved strains, while genetically homogeneous, exhibited many polymorphic m6A epiloci. There was no strong support for a genetic control of methylation changes in our experiment, and no clear evidence of parallel environmentally induced or environmentally selected methylation changes at specific epiloci was found. Both genetic and epigenetic variants were associated with some phenotypic traits. Overall, our results suggest that both genetic and adenine methylation changes have the potential to contribute to phenotypic adaptation in S. marcescens, but that any environmentally induced epigenetic change occurring in our experiment would probably have been quite labile.

摘要

表观遗传修饰可以促进适应，但遗传和表观遗传变异的相对贡献是未知的。先前关于表观遗传变化在真核生物适应中的作用的研究几乎完全集中在胞嘧啶甲基化（m5C）上，而原核生物表现出更丰富的甲基转移酶系统，靶向腺嘌呤（m6A）或胞嘧啶（m4C，m5C）。原核生物中的 DNA 甲基化具有多种作用，但其在适应中的潜在作用仍需进一步研究。我们使用粘质沙雷氏菌克隆的单分子实时测序收集表型、遗传和表观遗传数据在对比温度下经历了实验进化，以研究环境与遗传、表观遗传和表型变化之间的关系。GATC 基序（m6A 甲基化的主要靶标）和可变 m6A epiloci 的基因组分布表明 m6A 甲基化与粘质沙门氏菌基因表达调控之间存在潜在联系. 进化的菌株，虽然在遗传上是同质的，但表现出许多多态性 m6A 表皮。在我们的实验中，对甲基化变化的遗传控制没有强有力的支持，并且没有发现在特定的外发处平行的环境诱导或环境选择的甲基化变化的明确证据。遗传和表观遗传变异都与一些表型特征相关。总体而言，我们的结果表明遗传和腺嘌呤甲基化变化都有可能促进粘质沙门氏菌的表型适应，但在我们的实验中发生的任何环境诱导的表观遗传变化都可能非常不稳定。