97 Dissection of Evolution of Cis-Regulatory Elements and Its Application on Genetic Control of Complex Traits in Farm Animals

Abstract Functional Annotation of Animal Genomes (FAANG) has made significant progress on the improvement of the annotation of the functional elements, particularly non-coding regions in farm animal genomes. Different epigenomes including ChIP-seq for 4 histone marks, ATAC-seq, CTCF-seq, RNA-seq, and Hi-C across different tissues in different animal species were generated. Thousands of cis-regulatory elements including promoters and enhancers across different tissues in different species were identified and annotated. A comprehensive characterization and comparison of cis-regulatory elements across tissues and species can help us understand the genetic and evolutionary basis of complex phenotypes. Yet, attempts to dissect the evolution of regulatory elements have generally been small, both regarding the number of tissues and species compared. We demonstrate that genomic variants associated with complex traits and adaptive evolution in farm animals are significantly enriched in active promoters and enhancers. Further analysis suggests that the regulators were significantly enriched in evolutionary breakpoint regions (EBRs) in a tissue-specific and regulator-specific manner. Furthermore, we reveal distinct tissue-specific regulatory elements play important roles in domestication processes. Finally, we provide biological insights on tissue-specific regulatory conservation, and by integrating genome-wide association studies on complex traits, we demonstrate that comparative epigenomic analysis enhances our interpretations of complex traits variations in farm animals and provides novel insights on the role of regulatory elements on the functional conservation across species.