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
Donkey(Equus asinus)is an important livestock animal in China because of its draft and medicinal value.After a long period of natural and artificial selection,the variety and phenotype of donkeys have become abundant....Donkey(Equus asinus)is an important livestock animal in China because of its draft and medicinal value.After a long period of natural and artificial selection,the variety and phenotype of donkeys have become abundant.We clarified the genetic and demographic characteristics of Chinese domestic donkeys and the selection pressures by analyzing 78 whole genomes from 12 breeds.According to population structure,most Chinese domestic donkeys showed a dominant ancestral type.However,the Chinese donkeys still represented a significant geographical distribution trend.In the selective sweep,gene annotation,functional enrichment,and differential expression analyses between large and small donkey groups,we identified selective signals,including NCAPG and LCORL,which are related to rapid growth and large body size.Our findings elucidate the evolutionary history and formation of different donkey breeds and provide theoretical insights into the genetic mechanism underlying breed characteristics and molecular breeding programs of donkey clades.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.
基金supported by the Key Research&Development Plan of Shaanxi Province of China(2020NY-002)Dong-E-E-Jiao Co.Ltd(20191001)the National Natural Science Foundation of China(81770514)。
文摘Donkey(Equus asinus)is an important livestock animal in China because of its draft and medicinal value.After a long period of natural and artificial selection,the variety and phenotype of donkeys have become abundant.We clarified the genetic and demographic characteristics of Chinese domestic donkeys and the selection pressures by analyzing 78 whole genomes from 12 breeds.According to population structure,most Chinese domestic donkeys showed a dominant ancestral type.However,the Chinese donkeys still represented a significant geographical distribution trend.In the selective sweep,gene annotation,functional enrichment,and differential expression analyses between large and small donkey groups,we identified selective signals,including NCAPG and LCORL,which are related to rapid growth and large body size.Our findings elucidate the evolutionary history and formation of different donkey breeds and provide theoretical insights into the genetic mechanism underlying breed characteristics and molecular breeding programs of donkey clades.
