Dataset Information

Genetic variation in PTPN1 contributes to metabolic adaptation to high-altitude hypoxia in Tibetan migratory locusts.

ABSTRACT: Animal and human highlanders have evolved distinct traits to enhance tissue oxygen delivery and utilization. Unlike vertebrates, insects use their tracheal system for efficient oxygen delivery. However, the genetic basis of insect adaptation to high-altitude hypoxia remains unexplored. Here, we report a potential mechanism of metabolic adaptation of migratory locusts in the Tibetan Plateau, through whole-genome resequencing and functional investigation. A genome-wide scan revealed that the positively selected genes in Tibetan locusts are predominantly involved in carbon and energy metabolism. We observed a notable signal of natural selection in the gene PTPN1, which encodes PTP1B, an inhibitor of insulin signaling pathway. We show that a PTPN1 coding mutation regulates the metabolism of Tibetan locusts by mediating insulin signaling activity in response to hypoxia. Overall, our findings provide evidence for the high-altitude hypoxia adaptation of insects at the genomic level and explore a potential regulatory mechanism underlying the evolved metabolic homeostasis.

SUBMITTER: Ding D

PROVIDER: S-EPMC6255802 | biostudies-literature | 2018 Nov

REPOSITORIES: biostudies-literature

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Genetic variation in PTPN1 contributes to metabolic adaptation to high-altitude hypoxia in Tibetan migratory locusts.

Ding Ding D Liu Guangjian G Hou Li L Gui Wanying W Chen Bing B Kang Le L

Nature communications 20181126 1

Animal and human highlanders have evolved distinct traits to enhance tissue oxygen delivery and utilization. Unlike vertebrates, insects use their tracheal system for efficient oxygen delivery. However, the genetic basis of insect adaptation to high-altitude hypoxia remains unexplored. Here, we report a potential mechanism of metabolic adaptation of migratory locusts in the Tibetan Plateau, through whole-genome resequencing and functional investigation. A genome-wide scan revealed that the posit ...[more]

PMID: 30478313

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Project description:BackgroundTibetans have lived at very high altitudes for thousands of years, and have a distinctive suite of physiological traits that enable them to tolerate environmental hypoxia. Expanding awareness and knowledge of the differences in hematology, hypoxia-associated genes, immune system of people living at different altitudes and from different ethnic groups may provide evidence for the prevention of mountain sickness.MethodNinety-five Han people at mid-altitude, ninety-five Tibetan people at high-altitude and ninety-eight Han people at high-altitude were recruited. Red blood cell parameters, immune cells, the contents of cytokines, hypoxia-associated gene single nucleotide polymorphisms (SNPs) were measured.ResultsThe values of Hematocrit (HCT), Mean cell volume (MCV) and Mean cell hemoglobin (MCH) in red blood cell, immune cell CD19+ B cell number, the levels of cytokines Erb-B2 receptor tyrosine kinase 3 (ErbB3) and Tumor necrosis factor receptor II (TNF-RII) and the levels of hypoxia-associated factors Hypoxia inducible factor-1α (HIF-1α), Hypoxia inducible factor-2α (HIF-2α) and HIF prolyl 4-hydroxylase 2 (PHD2) were decreased, while the frequencies of SNPs in twenty-six Endothelial PAS domain protein 1 (EPAS1) and Egl-9 family hypoxia inducible factor 1 (EGLN1) were increased in Tibetan people at high-altitude compared with that of Han peoples at high-altitude. Furthermore, compared with mid-altitude individuals, high-altitude individuals showed lower blood cell parameters including Hemoglobin concentration (HGB), HCT, MCV and MCH, higher Mean cell hemoglobin concentration (MCHC), lower immune cells including CD19+ B cells, CD4+ T cells and CD4/CD8 ratio, higher immune cells containing CD8+ T cells and CD16/56NK cells, decreased Growth regulated oncogene alpha (GROa), Macrophage inflammatory protein 1 beta (MIP-1b), Interleukin-8 (IL-8), and increased Thrombomodulin, downregulated hypoxia-associated factors including HIF1α, HIF2α and PHD2, and higher frequency of EGLN1 rs2275279.ConclusionsThese results indicated that biological adaption to hypoxia at high altitude might have been mediated by changes in immune cells, cytokines, and hypoxia-associated genes during the evolutionary history of Tibetan populations. Furthermore, different responses to high altitude were observed in different ethnic groups, which may provide a useful knowledge to improve the protection of high-altitude populations from mountain sickness.

Dataset Information

Genetic variation in PTPN1 contributes to metabolic adaptation to high-altitude hypoxia in Tibetan migratory locusts.

Publications

Genetic variation in PTPN1 contributes to metabolic adaptation to high-altitude hypoxia in Tibetan migratory locusts.

Similar Datasets

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