Xin Li1,2,3,13, San-Gang He4,13, Wen-Rong Li4,13, Ling-Yun Luo1, Ze Yan1, Dong-Xin Mo1, Xing Wan1, Feng-Hua Lv1, Ji Yang1, Ya-Xi Xu1, Juan Deng1,5, Qiang-Hui Zhu1,2,3, Xing-Long Xie2,3, Song-Song Xu2,3, Chen-Xi Liu4, Xin-Rong Peng4, Bin Han4, Zhong-Hui Li4, Lei Chen4, Jian-Lin Han6,7, Xue-Zhi Ding8, Renqing Dingkao9, Yue-Feng Chu10, Jin-Yan Wu10, Li-Min Wang11,12, Ping Zhou11,12, Ming-Jun Liu4 and Meng-Hua Li1 1College of Animal Science and Technology, China Agricultural University, Beijing 100193, China; 2CAS Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences (CAS), Beijing 100101, China; 3College of Life Sciences, University of Chinese Academy of Sciences (UCAS), Beijing 100049, China; 4MOA Key Laboratory of Ruminant Genetics, Breeding and Reproduction, Ministry of Agriculture (MOA); Key Laboratory of Animal Technology of Xinjiang, Xinjiang Academy of Animal Science, Urumqi, 830000, China; 5College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China; 6CAAS-ILRI Joint Laboratory on Livestock and Forage Genetic Resources, Institute of Animal Science, Chinese Academy of Agricultural Sciences (CAAS), Beijing, 100193, China; 7Livestock Genetics Program, International Livestock Research Institute (ILRI), Nairobi, 00100, Kenya; 8MOA Key Laboratory of Veterinary Pharmaceutical Development of Ministry of Agriculture (MOA), Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences, Lanzhou, 730050, China; 9Institute of Animal Science and Veterinary Medicine, Gannan Tibetan Autonomous Prefecture, Hezuo, 747000, China; 10State Key Laboratory of Veterinary Etiological Biology, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, 730046, China; 11Institute of Animal Husbandry and Veterinary Medicine, Xinjiang Academy of Agricultural and Reclamation Sciences, Shihezi 832000, China; 12State Key Laboratory of Sheep Genetic Improvement and Healthy Production, Xinjiang Academy of Agricultural and Reclamation Sciences, Shihezi 832000, China

↵13 These authors contributed equally to this work.

Corresponding authors: menghua.licau.edu.cn, liumingjunxjaas.net Abstract

Understanding the genetic mechanisms of phenotypic variation in hybrids between domestic animals and their wild relatives may aid germplasm innovation. Here, we report the high-quality genome assemblies of a male Pamir argali (O. ammon polii, 2n = 56), a female Tibetan sheep (O. aries, 2n = 54), and a male hybrid of Pamir argali and domestic sheep, and the high-throughput sequencing of 425 ovine animals, including the hybrids of argali and domestic sheep. We detected genomic synteny between Chromosome 2 of sheep and two acrocentric chromosomes of argali. We revealed consistent satellite repeats around the chromosome breakpoints, which could have resulted in chromosome fusion. We observed many more hybrids with karyotype 2n = 54 than with 2n = 55, which could be explained by the selfish centromeres, the possible decreased rate of normal/balanced sperm, and the increased incidence of early pregnancy loss in the aneuploid ewes or rams. We identified genes and variants associated with important morphological and production traits (e.g., body weight, cannon circumference, hip height, and tail length) that show significant variations. We revealed a strong selective signature at the mutation (c.334C > A, p.G112W) in TBXT and confirmed its association with tail length among sheep populations of wide geographic and genetic origins. We produced an intercross population of 110 F2 offspring with varied number of vertebrae and validated the causal mutation by whole-genome association analysis. We verified its function using CRISPR-Cas9 genome editing. Our results provide insights into chromosomal speciation and phenotypic evolution and a foundation of genetic variants for the breeding of sheep and other animals.

Footnotes

[Supplemental material is available for this article.]

Article published online before print. Article, supplemental material, and publication date are at https://www.genome.org/cgi/doi/10.1101/gr.276769.122.

Freely available online through the Genome Research Open Access option.

Received April 1, 2022. Accepted July 29, 2022.