TY - JOUR

T1 - Pig genome functional annotation enhances the biological interpretation of complex traits and human disease

AU - Pan, Zhangyuan

AU - Yao, Yuelin

AU - Yin, Hongwei

AU - Cai, Zexi

AU - Wang, Ying

AU - Bai, Lijing

AU - Kern, Colin

AU - Halstead, Michelle

AU - Chanthavixay, Ganrea

AU - Trakooljul, Nares

AU - Wimmers, Klaus

AU - Sahana, Goutam

AU - Su, Guosheng

AU - Lund, Mogens Sandø

AU - Fredholm, Merete

AU - Karlskov-Mortensen, Peter

AU - Ernst, Catherine W.

AU - Ross, Pablo

AU - Tuggle, Christopher K.

AU - Fang, Lingzhao

AU - Zhou, Huaijun

N1 - Publisher Copyright: © 2021, The Author(s).

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

U2 - 10.1038/s41467-021-26153-7

DO - 10.1038/s41467-021-26153-7

M3 - Journal article

C2 - 34615879

AN - SCOPUS:85116454561

VL - 12

JO - Nature Communications

JF - Nature Communications

SN - 2041-1723

IS - 1

M1 - 5848

ER -