LCORL and STC2 Variants Increase Body Size and Growth Rate in Cattle and Other Animals

作者：Fengting Bai, Yudong Cai, Min Qi, Chen Liang, Linqian Pan, Yayi Liu, Yulong Feng, Xu Cao, Qimeng Yang, Gang Ren, Shaohua Jiao, Siqi Gao, Meixuan Lu, Xihong Wang, Rasmus Heller, Johannes A. Lenstra, Yu Jiang · 发表于：Genomics Proteomics & Bioinformatics · 年份：2025 · DOI：10.1093/gpbjnl/qzaf025 · 被引用次数：15 · 研究领域：CRISPR and Genetic Engineering、Animal Genetics and Reproduction、Viral Infectious Diseases and Gene Expression in Insects

Natural variants can significantly improve growth traits in livestock and serve as safe targets for gene editing, thus being applied in animal molecular design breeding. However, such safe and large-effect mutations are severely lacking. Using ancestral recombination graphs, we investigated recent selection signatures in beef cattle breeds, pinpointing sweep-driving variants in the LCORL and STC2 loci with notable effects on body size and growth rate. The ACT-to-A frameshift mutation in LCORL occurs mainly in central-European cattle, and stimulates growth. Remarkably, convergent truncating mutations were also found in commercial breeds of sheep, goats, pigs, horses, dogs, rabbits, and chickens. In the STC2 gene, we identified a missense mutation (A60P) located within the conserved region across vertebrates. We validated the two natural mutations in gene-edited mouse models, where both variants in homozygous carriers significantly increase the average weight by 11%. Our findings provide insights into a seemingly recurring gene target of body size enhancing truncating mutations across domesticated species, and offer valuable targets for gene editing-based breeding in animals.