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A comparative genomics study of carbohydrate/glucose metabolic genes: from fish to mammals.
Zhang Y
,
Qin C
,
Yang L
,
Lu R
,
Zhao X
,
Nie G
.
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BACKGROUND: Glucose plays a key role as an energy source in most mammals, but its importance in fish appears to be limited that so far seemed to belong to diabetic humans only. Several laboratories worldwide have made important efforts in order to better understand this strange phenotype observed in fish. However, the mechanism of carbohydrate/glucose metabolism is astonishingly complex. Why basal glycaemia is different between fish and mammals and how carbohydrate metabolism is different amongst organisms is largely uncharted territory. The utilization of comparative systems biology with model vertebrates to explore fish metabolism has become an essential approach to unravelling hidden in vivo mechanisms.
RESULTS: In this study, we first built a database containing 791, 593, 523, 666 and 698 carbohydrate/glucose metabolic genes from the genomes of Danio rerio, Xenopus tropicalis, Gallus gallus, Mus musculus and Homo sapiens, respectively, and most of these genes in our database are predicted to encode specific enzymes that play roles in defined reactions; over 57% of these genes are related to human type 2 diabetes. Then, we systematically compared these genes and found that more than 70% of the carbohydrate/glucose metabolic genes are conserved in the five species. Interestingly, there are 4 zebrafish-specific genes (si:ch211-167b20.8, CABZ01043017.1, socs9 and eif4e1c) and 1 human-specific gene (CALML6) that may alter glucose utilization in their corresponding species. Interestingly, these 5 genes are all carbohydrate regulation factors, but the enzymes themselves are involved in insulin regulation pathways. Lastly, in order to facilitate the use of our data sets, we constructed a glucose metabolism database platform ( http://101.200.43.1:10000/ ).
CONCLUSIONS: This study provides the first systematic genomic insights into carbohydrate/glucose metabolism. After exhaustive analysis, we found that most metabolic genes are conserved in vertebrates. This work may resolve some of the complexities of carbohydrate/glucose metabolic heterogeneity amongst different vertebrates and may provide a reference for the treatment of diabetes and for applications in the aquaculture industry.
31401014 National Natural Science Foundation of China, 31372545 National Natural Science Foundation of China, 31672671 National Natural Science Foundation of China, 14IRTSTHN013 Program for Innovative Research Team (in Science and Technology) in University of Henan Province, 2015FB177 Natural Science Foundation of Yunnan Province, qd15187 the PhD Start-up Fund of Henan Normal University
Fig. 1. Carbohydrate/glucose metabolic genes in Danio rerio (zebrafish), Xenopus tropicalis (frog), Gallus gallus (chicken), Mus musculus (mouse) and Homo sapiens (human). These diagrams are modified from VENNY (see Methods). Numbers in the overlapping and non-overlapping areas of the diagram indicate the number of genes found by overlapping or unique sets of orthologues and KEGG genes in each species. a Venn diagram of 791 zebrafish carbohydrate/glucose metabolic genes, which are merged with 545 zebrafish KEGG database genes and human (676), mouse (637), chicken (418) and frog (352) KEGG resource gene orthologues. b Venn diagram of 593 frog carbohydrate/glucose metabolic genes, which are merged with 352 frog KEGG database genes and human (676), mouse (637), chicken (418) and zebrafish (545) KEGG resource gene orthologues. c-e Similar to the data mining in zebrafish and frog, there are 523, 666 and 698 carbohydrate/glucose genes in chicken, mouse and human, respectively. f The table gives an overall measure of how many genes were found in each organism. The gene list can be seen in Additional file 1: Table S1
Fig. 2. Disease annotation of 698 human carbohydrate/glucose metabolic genes using DAVID. The chart displays part of the significant enrichment analysis of disease in human carbohydrate/glucose metabolic gene database. The x-axis shows the gene number involved in the annotation terms. The y-axis represents the disease terms. One star denotes Pâ<â0.05, whereas three stars denote Pâ<â0.0001
Fig. 3. Venn diagram of the relationship between carbohydrate/glucose metabolic genes and type 2 diabetes-associated genes. a Comparison of 698 human carbohydrate/glucose metabolic genes with 2620 human T2D-related genes (400 of 698 carbohydrate/glucose metabolic genes overlapped with T2D genes). b Similar to the phenomenon in human genes, 388 of 666 mouse carbohydrate/glucose metabolic genes were related to T2D. c In chicken, 313 carbohydrate/glucose metabolic genes were associated with T2D. d In frog, 336 carbohydrate/glucose metabolic genes overlapped with 2024 T2D-related genes. e Similarly, 464 zebrafish carbohydrate/glucose metabolic genes were involved in T2D. Abbreviation: MET- carbohydrate/glucose metabolism. All genes are shown in Additional file 6: Table S5
Fig. 4. The location of si:ch211-167b20.8, socs9, eif4e1c and CALML6 in the insulin signaling pathway. Zebrafish-specific si:ch211-167b20.8 and human-specific CALML6, encoding PP1 and PHK, respectively, which are two proteins that play opposite roles in insulin pathways. Zebrafish-specific genes are shaded in red, human-specific CALML6 is shown in the green box
Fig. 5. The study flowchart of this article. Methods are shown in brackets
Abdelmalek,
Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes.
2012, Pubmed
Abdelmalek,
Higher dietary fructose is associated with impaired hepatic adenosine triphosphate homeostasis in obese individuals with type 2 diabetes.
2012,
Pubmed
Agius,
Dietary carbohydrate and control of hepatic gene expression: mechanistic links from ATP and phosphate ester homeostasis to the carbohydrate-response element-binding protein.
2016,
Pubmed
Agrawal,
T2D-Db: an integrated platform to study the molecular basis of Type 2 diabetes.
2008,
Pubmed
Bakkers,
An important developmental role for oligosaccharides during early embryogenesis of cyprinid fish.
1997,
Pubmed
,
Xenbase
Basaranoglu,
Carbohydrate intake and nonalcoholic fatty liver disease: fructose as a weapon of mass destruction.
2015,
Pubmed
Bindea,
ClueGO: a Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks.
2009,
Pubmed
Capiotti,
Persistent impaired glucose metabolism in a zebrafish hyperglycemia model.
2014,
Pubmed
Cardoso,
Fish genomes provide novel insights into the evolution of vertebrate secretin receptors and their ligand.
2014,
Pubmed
Chen,
Cloning and characterization of human CAGLP gene encoding a novel EF-hand protein.
2004,
Pubmed
Chen,
VennDiagram: a package for the generation of highly-customizable Venn and Euler diagrams in R.
2011,
Pubmed
de Graaf,
Nutritional systems biology modeling: from molecular mechanisms to physiology.
2009,
Pubmed
Doege,
Characterization of human glucose transporter (GLUT) 11 (encoded by SLC2A11), a novel sugar-transport facilitator specifically expressed in heart and skeletal muscle.
2001,
Pubmed
Dupont,
Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle.
2016,
Pubmed
Elo,
Larval zebrafish as a model for glucose metabolism: expression of phosphoenolpyruvate carboxykinase as a marker for exposure to anti-diabetic compounds.
2007,
Pubmed
Exton,
Mechanisms of hormonal regulation of hepatic glucose metabolism.
1987,
Pubmed
Gonçalves,
Genome-wide analyses of chitin synthases identify horizontal gene transfers towards bacteria and allow a robust and unifying classification into fungi.
2016,
Pubmed
Goran,
The obesogenic effect of high fructose exposure during early development.
2013,
Pubmed
Gut,
LITTLE FISH, BIG DATA: ZEBRAFISH AS A MODEL FOR CARDIOVASCULAR AND METABOLIC DISEASE.
2017,
Pubmed
Hansen,
Polymorphism in the glycogen-associated regulatory subunit of type 1 protein phosphatase (PPP1R3) gene and insulin sensitivity.
2000,
Pubmed
Hediger,
The ABCs of solute carriers: physiological, pathological and therapeutic implications of human membrane transport proteinsIntroduction.
2004,
Pubmed
Hers,
Mechanisms of blood glucose homeostasis.
1990,
Pubmed
Hruz,
Structural analysis of the GLUT1 facilitative glucose transporter (review).
2001,
Pubmed
Huang,
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources.
2009,
Pubmed
Jin,
Global identification and comparative analysis of SOCS genes in fish: insights into the molecular evolution of SOCS family.
2008,
Pubmed
Joost,
The extended GLUT-family of sugar/polyol transport facilitators: nomenclature, sequence characteristics, and potential function of its novel members (review).
2001,
Pubmed
Joost,
Nomenclature of the GLUT/SLC2A family of sugar/polyol transport facilitators.
2002,
Pubmed
Joshi,
Phylogenetic analysis of eIF4E-family members.
2005,
Pubmed
Koo,
Dietary fructose induces a wide range of genes with distinct shift in carbohydrate and lipid metabolism in fed and fasted rat liver.
2008,
Pubmed
Kovach,
Mitochondrial Ultrastructure and Glucose Signaling Pathways Attributed to the Kv1.3 Ion Channel.
2016,
Pubmed
Kriventseva,
OrthoDB v8: update of the hierarchical catalog of orthologs and the underlying free software.
2015,
Pubmed
Leroux,
Transcriptional and translational mechanisms of cytochrome b5 reductase isoenzyme generation in humans.
2001,
Pubmed
Luo,
Pathview: an R/Bioconductor package for pathway-based data integration and visualization.
2013,
Pubmed
Marchitti,
Non-P450 aldehyde oxidizing enzymes: the aldehyde dehydrogenase superfamily.
2008,
Pubmed
Meyer,
From 2R to 3R: evidence for a fish-specific genome duplication (FSGD).
2005,
Pubmed
Moon,
Glucose intolerance in teleost fish: fact or fiction?
2001,
Pubmed
Mueckler,
Facilitative glucose transporters.
1994,
Pubmed
Ning,
Mechanisms and metabolic regulation of PPARα activation in Nile tilapia (Oreochromis niloticus).
2016,
Pubmed
Osundiji,
Hypothalamic glucose sensing and glycaemic disease.
2011,
Pubmed
Panserat,
Metformin improves postprandial glucose homeostasis in rainbow trout fed dietary carbohydrates: a link with the induction of hepatic lipogenic capacities?
2009,
Pubmed
Pilkis,
The role of cyclic AMP in rapid and long-term regulation of gluconeogenesis and glycolysis.
1988,
Pubmed
Plagnes-Juan,
Insulin regulates the expression of several metabolism-related genes in the liver and primary hepatocytes of rainbow trout (Oncorhynchus mykiss).
2008,
Pubmed
Polakof,
How Tom Moon's research highlighted the question of glucose tolerance in carnivorous fish.
2016,
Pubmed
Polakof,
Glucose metabolism in fish: a review.
2012,
Pubmed
Polakof,
Glucose homeostasis is impaired by a paradoxical interaction between metformin and insulin in carnivorous rainbow trout.
2009,
Pubmed
Polakof,
Glucosensing and glucose homeostasis: from fish to mammals.
2011,
Pubmed
Polakof,
In vitro evidences for glucosensing capacity and mechanisms in hypothalamus, hindbrain, and Brockmann bodies of rainbow trout.
2007,
Pubmed
Robalino,
Two zebrafish eIF4E family members are differentially expressed and functionally divergent.
2004,
Pubmed
,
Xenbase
Ruiz-Herrera,
Evolution and phylogenetic relationships of chitin synthases from yeasts and fungi.
2002,
Pubmed
Sartorelli,
Dietary fructose, fruits, fruit juices and glucose tolerance status in Japanese-Brazilians.
2009,
Pubmed
Sayers,
Database resources of the National Center for Biotechnology Information.
2011,
Pubmed
Shannon,
Cytoscape: a software environment for integrated models of biomolecular interaction networks.
2003,
Pubmed
Softic,
Role of Dietary Fructose and Hepatic De Novo Lipogenesis in Fatty Liver Disease.
2016,
Pubmed
Tang,
Chitin is endogenously produced in vertebrates.
2015,
Pubmed
Vasiliou,
Analysis and update of the human aldehyde dehydrogenase (ALDH) gene family.
2005,
Pubmed
Wang,
The association between PPP1R3 gene polymorphisms and type 2 diabetes mellitus.
2001,
Pubmed
Xia,
A common variant in PPP1R3 associated with insulin resistance and type 2 diabetes.
1998,
Pubmed
Yang,
T2D@ZJU: a knowledgebase integrating heterogeneous connections associated with type 2 diabetes mellitus.
2013,
Pubmed
Zhao,
Nutritional systems biology of type 2 diabetes.
2015,
Pubmed
