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 ...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.展开更多
基金supported by the National Key R&D Program of China(Grant Nos.2022YFF1000100 and 2023YF D1300402)the National Natural Science Foundation of China(Grant No.U21A20120)the Shaanxi Livestock and Poultry Breeding Double-chain Fusion Key Project,China(Grant No.2022GD-TSLD-46-0401).
文摘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.
