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An ancient deletion in the ABO gene affects the composition of the porcine microbiome by altering intestinal N-acetyl-galactosamine concentrations

By Hui Yang, Jinyuan Wu, Xiaochang Huang, Yunyan Zhou, Yifeng Zhang, Min Liu, Qin Liu, Shanlin Ke, Maozhang He, Hao Fu, Shaoming Fang, Xinwei Xiong, Hui Jiang, Zhe Chen, Zhongzi Wu, Huanfa Gong, Xinkai Tong, Yizhong Huang, Junwu Ma, Jun Gao, Carole Charlier, Wouter Coppieters, Lev Shagam, Zhiyan Zhang, Huashui Ai, Bin Yang, Michel Georges, Congying Chen, Lusheng Huang

Posted 16 Jul 2020
bioRxiv DOI: 10.1101/2020.07.16.206219

We have generated a large heterogenous stock population by intercrossing eight divergent pig breeds for multiple generations. We have analyzed the composition of the intestinal microbiota at different ages and anatomical locations in > 1,000 6th- and 7th- generation animals. We show that, under conditions of exacerbated genetic yet controlled environmental variability, microbiota composition and abundance of specific taxa (including Christensenellaceae) are heritable in this monogastric omnivore. We fine-map a QTL with major effect on the abundance of Erysipelotrichaceae to chromosome 1q and show that it is caused by a common 2.3-Kb deletion inactivating the ABO acetyl-galactosaminyl-transferase gene. We show that this deletion is a trans-species polymorphism that is ≥3.5 million years old and under balancing selection. We demonstrate that it acts by decreasing the concentrations of N-acetyl-galactosamine in the cecum thereby reducing the abundance of Erysipelotrichaceae strains that have the capacity to import and catabolize N-acetyl-galactosamine. ### Competing Interest Statement The authors have declared no competing interest.

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