Global pangenome analysis highlights the critical role of structural variants in cattle improvement and identifies a unique event as a novel enhancer in IGFBP7+ cells

Authors: DAI, SHOULU - Huazhong Agricultural University; ZHAO, PENGJU - Zhejiang University; LI, WENHAO - Huazhong Agricultural University; PENG, LINGWEI - Huazhong Agricultural University; JIANG, ENHUI - Northwest A&f University; DU, YUQIN - Huazhong Agricultural University; ZHANG, WENGANG - Collaborator; DAI, XUELEI - Collaborator; YANG, LIU - University Of Maryland; LI, ZHIQIANG - Collaborator; XU, LINJING - Huazhong Agricultural University; LAN, XIANYONG - Northwest A&f University; LYU, WENFA - Jilin Agricultural University; YANG, LIGUO - Huazhong Agricultural University; FANG, LINGZHAO - Aarhus University; Liu, Ge; ZHOU, YANG - Huazhong Agricultural University

Submitted to: Molecular Biology and Evolution
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 7/31/2025
Publication Date: 8/19/2025
Citation: Dai, S., Zhao, P., Li, W., Peng, L., Jiang, E., Du, Y., Zhang, W., Dai, X., Yang, L., Li, Z., Xu, L., Lan, X., Lyu, W., Yang, L., Fang, L., Liu, G., Zhou, Y. 2025. Global pangenome analysis highlights the critical role of structural variants in cattle improvement and identifies a unique event as a novel enhancer in IGFBP7+ cells. Molecular Biology and Evolution. https://doi.org/10.1093/molbev/msaf205.
DOI: https://doi.org/10.1093/molbev/msaf205

Interpretive Summary: Structural variations (SVs) are changes in the genome that play a significant role in the genetic differences seen in cattle worldwide. In our study of over 2,500 cattle from 82 breeds, we found that SVs, especially those not associated with common genetic markers, help explain differences in traits such as adaptability and productivity, offering new insights into how cattle adapt to various environments. This study will be valuable for farmers, scientists, and policymakers working to improve animal health and production through genome-enabled selection.

Technical Abstract: The phenotypic diversity of worldwide cattle populations can be explained by a combination of SNPs, SVs, and other genetic factors. However, the importance of SVs has not been widely explored until recent attention shifted to the pangenome. In this study, we simultaneously analyzed the roles of SNPs and SVs in the population structures and phenotypic formation of global cattle using 2,573 individuals from 82 breeds based on a pangenome graph. We demonstrated that SVs, like SNPs, effectively explain the population structure of cattle. Genomic regions under strong selection, identified using both SNPs and SVs, consistently revealed footprints associated with human selection of economic traits in European improved cattle and natural selection of genetic adaptations in Asia and Africa when comparing across cattle populations. Notably, ~40.14% of SVs were not tagged (r2 = 0.6, minor allele frequency = 0.01) by nearby SNPs within 1Mb. These "orphan" SVs uncovered additional genetic signals and were shown to represent recent mutations associated with specific selection pressures or local environmental adaptability. For SVs tagged by SNPs, they may play causal and dominant roles in regions under selection. For example, a notable SNP-tagged SV functions as an enhancer for the IGFBP7 gene, regulating fat deposition through IGFBP7+ cells. This mechanism underlies differences in economic traits and local adaptability across cattle populations. Our integrated approach highlights the unique and complementary roles of SVs in shaping genetic diversity, offering novel insights into adaptation, selection, and strategies for improving cattle populations, particularly in developing countries and regions.