The giant panda(Ailuropoda melanoleuca)is an iconic bear native to China,famous for eating almost exclusively bamboo.This unusual dietary behavior for a carnivore is enabled by several key adaptations including low physical activity,reduced organ sizes and hypothyroidism leading to lowered energy expenditure.These adaptive phenotypes have been hypothesized to arise from a panda-unique single-nucleotide mutation in the dual-oxidase 2(DUOX2)gene,involved in thyroid hormone synthesis.To test this hypothesis,we created genome-edited mice carrying the same point mutation as the panda and investigated its effect on metabolic phenotype.Homozygous mice were 27％smaller than heterozygous and wild-type ones,had 13％lower body mass-adjusted food intake,55％decreased physical activity,lower mass of kidneys(11％)and brain(5％),lower serum thyroxine(T4:36％),decreased absolute(12％)and mass-adjusted(5％)daily energy expenditure,and altered gut microbiota.Supplementation with T4 reversed the effects of the mutation.This work uses a state-of-the-art genome editing approach to demonstrate the link between a single-nucleotide mutation in a key endocrine-related gene and profound adaptive changes in the metabolic phenotype,with great importance in ecology and evolution.

Agata M.Rudolf;Qi Wu;Li Li;Jun Wang;Yi Huang;Jacques Togo;Christopher Liechti;Min Li;Chaoqun Niu;Yonggang Nie;Fuwen Wei;John R.Speakman

State Key Laboratory of Molecular Development,Institute of Genetics and Developmental Biology,Chinese Academy of Sciences,Beijing 100101,China;Institute of Zoology,Chinese Academy of Sciences,Beijing 100101,China;Institute of Microbiology,Chinese Academy of Sciences,Beijing 100101,China;Institute of Biological and Environmental Sciences,University of Aberdeen,Aberdeen AB24 2TZ,UK;Centre of Excellence for Animal Ecology and Genetics,Chinese Academy of Sciences,Kunming 650223,China;Shenzhen Key Laboratory of Metabolic Health,Center for Energy Metabolism and Reproduction,Shenzhen Institute of Advanced Technology,Chinese Academy of Sciences,Shenzhen 518055,China

国家科学评论（英文版）

[1]Agata M.Rudolf;Qi Wu;Li Li;Jun Wang;Yi Huang;Jacques Togo;Christopher Liechti;Min Li;Chaoqun Niu;Yonggang Nie;Fuwen Wei;John R.Speakman-.A single nucleotide mutation in the dual-oxidase 2(DUOX2)gene causes some of the panda's unique metabolic phenotypes)[J].国家科学评论（英文版）,2022(02):29-37

Homozygous

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