A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes. Issue 2 (15th July 2021)

• Record Type: Journal Article
• Authors: Rudolf, Agata M; Wu, Qi; Li, Li; Wang, Jun; Huang, Yi; Togo, Jacques; Liechti, Christopher; Li, Min; Niu, Chaoqun; Nie, Yonggang; Wei, Fuwen; Speakman, John R
• Is Part Of: National science review. Volume 9:Issue 2(2022)
• Publication Date: 2021-07-15
• Subjects: giant panda -- DUOX2 mutation -- metabolic rate -- thyroid hormones -- DUOX2 -- mice and microbiota; Science -- Periodicals; 505
• DOI: 10.1093/nsr/nwab125
• Languages: English
• ISSNs: 2095-5138

Abstract

Abstract: 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.