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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 P < 0.05, whereas three stars denote P < 0.0001
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
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