a Avian Behavioral Genomics and Physiology Group, IFM Biology , Linköping University , Linköping , Sweden.
b Animal Biotechnology Laboratory, Animal Science Department , University of São Paulo (USP)/Luiz de Queiroz College of Agriculture (ESALQ) , Piracicaba , São Paulo , Brazil.
Epigenetics. 2019 Jul;14(7):685-707. doi: 10.1080/15592294.2019.1609868. Epub 2019 May 9.
DNA methylation in CpGs dinucleotides is associated with high mutability and disappearance of CpG sites during evolution. Although the high mutability of CpGs is thought to be relevant for vertebrate evolution, very little is known on the role of CpG-related mutations in the genomic diversification of vertebrates. Our study analysed genetic differences in chickens, between Red Junglefowl (RJF; the living closest relative to the ancestor of domesticated chickens) and domesticated breeds, to identify genomic dynamics that have occurred during the process of their domestication, focusing particularly on CpG-related mutations. Single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) between RJF and these domesticated breeds were assessed in a reduced fraction of their genome. Additionally, DNA methylation in the same fraction of the genome was measured in the sperm of RJF individuals to identify possible correlations with the mutations found between RJF and the domesticated breeds. Our study shows that although the vast majority of CpG-related mutations found relate to CNVs, CpGs disproportionally associate to SNPs in comparison to CNVs, where they are indeed substantially under-represented. Moreover, CpGs seem to be hotspots of mutations related to speciation. We suggest that, on the one hand, CpG-related mutations in CNV regions would promote genomic 'flexibility' in evolution, i.e., the ability of the genome to expand its functional possibilities; on the other hand, CpG-related mutations in SNPs would relate to genomic 'specificity' in evolution, thus, representing mutations that would associate with phenotypic traits relevant for speciation.
在 CpG 二核苷酸中，DNA 甲基化与高突变率和 CpG 位点在进化过程中的缺失有关。虽然 CpG 的高突变率被认为与脊椎动物的进化有关，但对于 CpG 相关突变在脊椎动物基因组多样化中的作用知之甚少。我们的研究分析了红原鸡（RJF；与驯化鸡祖先最接近的现存近亲）和驯化品种之间的遗传差异，以鉴定在驯化过程中发生的基因组动态，特别关注 CpG 相关突变。在它们基因组的一小部分中评估了 RJF 与这些驯化品种之间的单核苷酸多态性（SNP）和拷贝数变异（CNV）。还测量了 RJF 个体精子中同一基因组部分的 DNA 甲基化，以鉴定与 RJF 和驯化品种之间发现的突变可能存在的相关性。我们的研究表明，尽管绝大多数发现的 CpG 相关突变与 CNV 有关，但与 CNV 相比，CpG 与 SNPs 的相关性不成比例，实际上它们的数量大大减少。此外，CpG 似乎是与物种形成相关的突变热点。我们认为，一方面，CNV 区域中的 CpG 相关突变会促进进化中的基因组“灵活性”，即基因组扩展其功能可能性的能力；另一方面，SNP 中的 CpG 相关突变与进化中的基因组“特异性”有关，因此，代表与物种形成相关的表型特征相关的突变。
