Online

Bhattarai, Suraj

Animal and Veterinary Sciences

2023

Ph. D.

This dissertation examines DNA methylation's role, an important epigenetic modification, in livestock traits like growth and disease resistance. DNA methylation, which affects gene expression without altering DNA sequence, was studied for its conserved pattern, tissue specificity, and evolutionary impact in ruminant livestock. Firstly, we studied DNA methylation in the 5' AMP-activated protein kinase (AMPK) gene family in liver tissues from various cattle breeds and American bison. The methylation pattern and level of PRKAA1 and PRKAB1 genes in the AMPK family were found to be conserved across breeds, suggesting a critical role in maintaining the function of an evolutionarily conserved protein. Next, we explored DNA methylome and tissue-specific methylation in the cerebellum, liver, and spleen of crossbred sheep using whole-genome bisulfite sequencing. Distinct hypomethylated regions and features of non-CG methylation were discovered. Notably, non-CG methylation was highest in the cerebellum, hinting at a role in regulating gene expression and functional annotation of tissues. Lastly, we compared methylation profiles between domesticated cattle and American bison. Bison had lower CG site methylation and higher non-CG methylation than cattle breeds. Differentially methylated cytosines (DMCs) were identified in genic regions, with extreme DMCs present in genes linked to various biological functions. Bison also had lower methylation in transposable elements, implying their role in preserving genetic diversity despite population bottleneck events. Overall, our findings shed light on the significant role that DNA methylation plays in shaping the evolution, development, and performance traits of ruminant livestock. The conserved DNA methylation in the AMPK gene family across diverse cattle breeds underscores its potential role in maintaining essential cellular functions. Moreover, the tissue-specific DNA methylation profiles unveiled in sheep deepens our understanding of epigenetic regulation in livestock. In addition, the comparison of methylation profiles between domesticated cattle and bison provides valuable insights into the epigenetic consequences of domestication and its potential influence on phenotypic diversity. These findings present DNA methylation as an important area for exploration in future livestock improvement strategies and could pave the way for targeted breed enhancement and sustainable livestock management.