A 14-bp motif in the KIT active promoter region is critical for melanin accumulation in yaks, mice, and humans
Xinfeng Liu,
Tongcheng Wang,
Zeyu Zheng,
Congcong Dong,
Wenyu Liu,
Zhimin Niu,
Yingbo Yang,
Xiaoyun Wu,
Qiang Qiu,
Yongzhi Yang,
Kexin Li,
Johannes A. Lenstra,
Ping Yan,
Minghui Kang,
Bowen Li,
Lingzhao Fang,
Jianquan Liu
Affiliations
Xinfeng Liu
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Tongcheng Wang
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Zeyu Zheng
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Congcong Dong
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Wenyu Liu
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Zhimin Niu
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Yingbo Yang
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Xiaoyun Wu
Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences
Qiang Qiu
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Yongzhi Yang
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Kexin Li
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Johannes A. Lenstra
Faculty of Veterinary Medicine, Utrecht University
Ping Yan
Key Laboratory of Animal Genetics and Breeding On Tibetan Plateau, Ministry of Agriculture and Rural Affairs, Lanzhou Institute of Husbandry and Pharmaceutical Sciences, Chinese Academy of Agricultural Sciences
Minghui Kang
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Bowen Li
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Lingzhao Fang
Center for Quantitative Genetics and Genomics, Aarhus University
Jianquan Liu
State Key Laboratory of Herbage lmprovement and Grassland Agro-ecosystems, College of Ecology, Lanzhou University
Abstract Background Animal pigmentation serves as an excellent model for studying genetics, development, and evolution. Among yak breeds, the all-white yak breed (Bos grunniens) is the only indigenous variety with pristine white fur, in stark contrast to the black coat color of the wild yak and most domesticated yaks. Results Using whole-genome sequencing data from 387 yaks, we analyzed the population genetic structure of all-white yaks and discovered that they clustered into two distinct genetic groups. Further, by conducting a genome-wide association study (GWAS) based on whole-genome variants (SNPs and indels) between all-white and wild-type yaks, we identified a 14-bp deletion in the promoter of KIT, which decreased its expression in all-white yaks. The following knock-in experiments in mouse confirmed that the absence of the yak 14-bp motif decreases the expression of KIT. Deletion of a human orthologue of the yak 14-bp motif by using the CRISPR/Cas9 system reduces the melanin accumulation in human melanoma cells. Conclusions Overall, our study revealed the genetic basis of all-white yaks and underscored the importance of studying livestock phenotypes to uncover conserved genetic regulators in mammals.
