Urbanization represents a fierce driver of phenotypic change, yet the molecular mechanisms underlying observed phenotypic patterns are poorly understood. Epigenetic changes are expected to facilitate more rapid adaption to changing or novel environments, such as our towns and cities, compared with slow changes in gene sequence. A comparison of liver and blood tissue from great tits Parus major originating from an urban and a forest site demonstrated that urbanization is associated with variation in genome‐wide patterns of DNA methylation. Combining reduced representation bisulphite sequencing with transcriptome data, we revealed habitat differences in DNA methylation patterns that suggest a regulated and coordinated response to the urban environment. In the liver, genomic sites that were differentially methylated between urban‐ and forest‐dwelling birds were over‐represented in regulatory regions of the genome and more likely to occur in expressed genes. DNA methylation levels were also inversely correlated with gene expression at transcription start sites. Furthermore, differentially methylated CpG sites, in liver, were over‐represented in pathways involved in (i) steroid biosynthesis, (ii) superoxide metabolism, (iii) secondary alcohol metabolism, (iv) chylomicron remodelling, (v) cholesterol transport, (vi) reactive oxygen species (ROS) metabolic process and (vii) epithelial cell proliferation. This corresponds with earlier studies identifying diet and exposure to ROS as two of the main drivers of divergence between organisms in urban and nonurban environments. Conversely, in blood, sites that were differentially methylated between urban‐ and forest‐dwelling birds were under‐represented in regulatory regions, more likely to occur in nonexpressed genes and not over‐represented in specific biological pathways. It remains to be determined whether diverging patterns of DNA methylation represent adaptive evolutionary responses and whether the conclusions can be more widely attributed to urbanization.

中文翻译：

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城市化与小型雀形目鸟类 DNA 甲基化的改变有关


城市化是表型变化的强烈驱动力，但观察到的表型模式背后的分子机制却知之甚少。与基因序列的缓慢变化相比，表观遗传变化预计将有助于更快地适应不断变化或新的环境，例如我们的城镇和城市。对源自城市和森林地区的大山雀肝脏和血液组织的比较表明，城市化与全基因组 DNA 甲基化模式的变化有关。将简化代表性亚硫酸氢盐测序与转录组数据相结合，我们揭示了 DNA 甲基化模式的栖息地差异，这表明对城市环境的调节和协调反应。在肝脏中，城市鸟类和森林鸟类之间差异甲基化的基因组位点在基因组调控区域中过多，并且更可能出现在表达基因中。 DNA 甲基化水平也与转录起始位点的基因表达呈负相关。此外，肝脏中差异甲基化的 CpG 位点在涉及 (i) 类固醇生物合成、(ii) 超氧化物代谢、(iii) 次级酒精代谢、(iv) 乳糜微粒重塑、(v) 胆固醇转运的途径中过度表达。 vi) 活性氧 (ROS) 代谢过程和 (vii) 上皮细胞增殖。这与早期研究相一致，该研究确定饮食和接触活性氧是城市和非城市环境中生物体差异的两个主要驱动因素。 相反，在血液中，城市鸟类和森林鸟类之间差异甲基化的位点在调控区域中代表性不足，更有可能出现在非表达基因中，并且在特定生物途径中代表性不高。 DNA甲基化的不同模式是否代表适应性进化反应以及这些结论是否可以更广泛地归因于城市化仍有待确定。