A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes

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

doi:10.1093/nsr/nwab125

A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes

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^*

^*Corresponding author for this work

CAS - Institute of Genetics and Developmental Biology
CAS - Institute of Zoology
CAS - Institute of Microbiology
University of Aberdeen
Chinese Academy of Sciences

Research output: Contribution to journal › Article › peer-review

12 Citations (Scopus)

4 Downloads (Pure)

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.

Original language	English
Article number	nwab125
Number of pages	9
Journal	National Science Review
Volume	9
Issue number	2
Early online date	15 Jul 2021
DOIs	https://doi.org/10.1093/nsr/nwab125
Publication status	Published - 1 Feb 2022

Bibliographical note

This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences (XDB13030100 and XDB29020000), the Creative Research Group Project of National Natural Science Foundation of China (31821001), the Key Project of the Chinese Academy of Sciences (QYZDB-SSW-SMC047), the National Key Research and Development Program of China (2018YFC2000500), the Chinese Academy of Sciences President's International Fellowship Initiative Postdoctoral Fellowship (to A.M.R.) and the President's International Fellowship Initiative Professorial and Wolfson Merit Award (to J.R.S.).

Data Availability Statement

The data underlying this article are available from the corresponding author John R. Speakman upon request, and are deposited in a public repository, Zenodo, accession number 10.5281/zenodo.4674583

Keywords

DUOX2
DUOX2 mutation
Giant panda
Metabolic rate
Mice and microbiota
Thyroid hormones

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Rudolf_etal_NSR_SingleNucleotideMutation_VOR
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Cite this

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title = "A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes",

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.",

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AU - Li, Li

AU - Wang, Jun

AU - Huang, Yi

AU - Togo, Jacques

AU - Liechti, Christopher

AU - Li, Min

AU - Niu, Chaoqun

AU - Nie, Yonggang

AU - Wei, Fuwen

AU - Speakman, John R.

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N2 - 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.

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ER -

A single nucleotide mutation in the dual-oxidase 2 (DUOX2) gene causes some of the panda's unique metabolic phenotypes

Abstract

Bibliographical note

Data Availability Statement

Keywords

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