Genome-Wide DNA Methylation Differences between Bos indicus and Bos taurus

SIMPLE SUMMARY: Domestic cattle are one of the indispensable economic animals in human production and life, and zebu (Bos indicus), as one type of the domestic cattle breeds, has unique characteristics, especially disease resistance and economic traits, but the epigenetic basis underlying zebu’s merit traits is still to be studied. Therefore, in this study, we used Yunnan zebu as a representative of zebu and analyzed the differences in DNA methylation between zebu and taurine cattle (Bos taurus) using whole-genome bisulfite sequencing technology. We found no significant differences in the DNA methylation patterns between the two cattle types but identified many pathways and candidate genes associated with disease, disease resistance, and economic traits. The results of this study may provide a foundation for further screening of characteristic epigenetic molecular markers in zebu, thus providing theoretical support for the genetic improvement of domestic cattle. ABSTRACT: Disease risk is a persistent problem in domestic cattle farming, while economic traits are the main concern. This study aimed to reveal the epigenetic basis for differences between zebu (Bos indicus) and taurine cattle (Bos taurus) in disease, disease resistance, and economic traits, and provide a theoretical basis for the genetic improvement of domestic cattle. In this study, whole genome bisulfite sequencing (WGBS) was used to analyze the whole-genome methylation of spleen and liver samples from Yunnan zebu and Holstein cattle. In the genome-wide methylation pattern analysis, it was found that the methylation pattern of all samples was dominated by the CG type, which accounted for >94.9%. The DNA methylation levels of different functional regions and transcriptional elements in the CG background varied widely. However, the methylation levels of different samples in the same functional regions or transcriptional elements did not differ significantly. In addition, we identified a large number of differentially methylation region (DMR) in both the spleen and liver groups, of which 4713 and 4663 were annotated to functional elements, and most of them were annotated to the intronic and exonic regions of genes. GO and KEGG functional analysis of the same differentially methylation region (DMG) in the spleen and liver groups revealed that significantly enriched pathways were involved in neurological, disease, and growth functions. As a result of the results of DMR localization, we screened six genes (DNM3, INPP4B, PLD, PCYT1B, KCNN2, and SLIT3) that were tissue-specific candidates for economic traits, disease, and disease resistance in Yunnan zebu. In this study, DNA methylation was used to construct links between genotypes and phenotypes in domestic cattle, providing useful information for further screening of epigenetic molecular markers in zebu and taurine cattle.