Bai, F.; Cai, Y.; Qiu, M.; Liang, C.; Pan, L.; Liu, Y.; Feng, Y.; Cao, X.; Yang, Q.; Ren, G.; Jiao, S.; Gao, S.; Lu, M.; Wang, X.; Heller, R.; Lenstra, J. A.; Jiang, Y.

Using ancestral recombination graphs, we investigated recent selection signatures in European 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, similar truncating mutations were found in seven of the other most important domesticated species, but not in most populations of wild relatives. In the STC2 locus, we identified a missense C-to-G mutation located within the conserved region across vertebrates. We validated the two natural mutations in gene-edited mouse models, where both variants in homozygous carriers 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.