Pig genome functional annotation enhances the biological interpretation of complex traits and human disease

Zhangyuan Pan, Yuelin Yao, Hongwei Yin, Zexi Cai, Ying Wang, Lijing Bai, Colin Kern, Michelle Halstead, Ganrea Chanthavixay, Nares Trakooljul, Klaus Wimmers, Goutam Sahana, Guosheng Su, Mogens Sandø Lund, Merete Fredholm, Peter Karlskov-Mortensen, Catherine W. Ernst, Pablo Ross, Christopher K. Tuggle, Lingzhao Fang () and Huaijun Zhou ()
Additional contact information
Zhangyuan Pan: University of California, Davis
Yuelin Yao: MRC Human Genetics Unit at the Institute of Genetics and Molecular Medicine, The University of Edinburgh
Hongwei Yin: Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Sciences
Zexi Cai: Center for Quantitative Genetics and Genomics, Faculty of Technical Sciences, Aarhus University
Ying Wang: University of California, Davis
Lijing Bai: Agricultural Genome Institute at Shenzhen, Chinese Academy of Agricultural Sciences
Colin Kern: University of California, Davis
Michelle Halstead: University of California, Davis
Ganrea Chanthavixay: University of California, Davis
Nares Trakooljul: Leibniz-Institute for Farm Animal Biology
Klaus Wimmers: Leibniz-Institute for Farm Animal Biology
Goutam Sahana: Center for Quantitative Genetics and Genomics, Faculty of Technical Sciences, Aarhus University
Guosheng Su: Center for Quantitative Genetics and Genomics, Faculty of Technical Sciences, Aarhus University
Mogens Sandø Lund: Center for Quantitative Genetics and Genomics, Faculty of Technical Sciences, Aarhus University
Merete Fredholm: Animal Genetics, Bioinformatics and Breeding, Department of Veterinary and Animal Sciences, University of Copenhagen
Peter Karlskov-Mortensen: Animal Genetics, Bioinformatics and Breeding, Department of Veterinary and Animal Sciences, University of Copenhagen
Catherine W. Ernst: Michigan State University
Pablo Ross: University of California, Davis
Christopher K. Tuggle: Iowa State University
Lingzhao Fang: MRC Human Genetics Unit at the Institute of Genetics and Molecular Medicine, The University of Edinburgh
Huaijun Zhou: University of California, Davis

Nature Communications, 2021, vol. 12, issue 1, 1-15

Abstract: Abstract The functional annotation of livestock genomes is crucial for understanding the molecular mechanisms that underpin complex traits of economic importance, adaptive evolution and comparative genomics. Here, we provide the most comprehensive catalogue to date of regulatory elements in the pig (Sus scrofa) by integrating 223 epigenomic and transcriptomic data sets, representing 14 biologically important tissues. We systematically describe the dynamic epigenetic landscape across tissues by functionally annotating 15 different chromatin states and defining their tissue-specific regulatory activities. We demonstrate that genomic variants associated with complex traits and adaptive evolution in pig are significantly enriched in active promoters and enhancers. Furthermore, we reveal distinct tissue-specific regulatory selection between Asian and European pig domestication processes. Compared with human and mouse epigenomes, we show that porcine regulatory elements are more conserved in DNA sequence, under both rapid and slow evolution, than those under neutral evolution across pig, mouse, and human. Finally, we provide biological insights on tissue-specific regulatory conservation, and by integrating 47 human genome-wide association studies, we demonstrate that, depending on the traits, mouse or pig might be more appropriate biomedical models for different complex traits and diseases.

Date: 2021
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DOI: 10.1038/s41467-021-26153-7

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