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Deduction and exploration of the evolution and function of vertebrate GFPT family

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Abstract

Background

Glutamine-fructose-6-phosphate aminotransferase (GFPT) is a key factor in the hexosamine metabolism pathway. It regulates the downstream factor O-GlcNAc to change cell function and plays an important role in the metabolism and immune process of tissues and organs. However, the evolutionary relationship of GFPT family proteins in vertebrates has not been elucidated.

Objective

To deduce and explore the evolution and function of vertebrate GFPT family.

Methods

18 GFPT sequences were obtained from Homo sapiens (H. sapiens), Trachypithecus francoisi (T. francoisi), Mus musculus (M. musculus), Rattus norvegicus (R. norvegicus), Gallus gallus (G. gallus), Zootoca vivipara (Z. vivipara), Xenopus tropicalis (X. tropicalis), Danio rerio (D. rerio), Rhincodon typus (R. typus), Plasmodium relictum from National Center for Biotechnology Information (NCBI). The physical and chemical characteristics and molecular evolution of GFPT family proteins and nucleic acid sequences were analyzed by ClustalX2, Gene Doc, MEGA-X, SMART, Datamonkey, R etc.

Results

Based on the neighbor-joining (NJ) phylogenetic tree and evolution fingerprints, GFPT family members of vertebrates can be divided into two groups: the GFPT1 group and the GFPT2 group. Seven positive selection sites were identified by IFEL and integrated methods mixed effects model of evolution (MEME) and fixed effects likelihood (REL). Finally, we predicted 28 phosphorylation sites and 18 ubiquitousness sites in the human GFPT1 sequence, 10 phosphorylation sites, and five ubiquitousness sites in GFPT2. Gene ontology (GO) analyzes the protein molecules and KEGG signaling pathways of vertebrates interacting with GFPT family proteins.

Conclusions

Our work confirmed that higher animals GFPT family may have differentiated GFPT1 and GFPT2, which meets their own functional needs. This knowledge answers the question what the origin and evolution of GFPT family in vertebrates and provided the basis for disease treatment and function research of GFPT protein.

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References

  • Aris-Brosou S, Rodrigue N (2019) A not-so-long introduction to computational molecular evolution. Methods Mol Biol 1910:71–117

    Article  CAS  PubMed  Google Scholar 

  • Bauché S, Vellieux G, Sternberg D, Fontenille MJ, De Bruyckere E, Davoine CS, Brochier G, Messéant J, Wolf L, Fardeau M et al (2017) Mutations in GFPT1-related congenital myasthenic syndromes are associated with synaptic morphological defects and underlie a tubular aggregate myopathy with synaptopathy. J Neurol 264(8):1791–1803

    Article  PubMed  CAS  Google Scholar 

  • Cvijović I, Good BH, Desai MM (2018) The effect of strong purifying selection on genetic diversity. Genetics 209(4):1235–1278

    Article  PubMed  PubMed Central  Google Scholar 

  • Delport W, Poon AFY, Frost SDW, Kosakovsky Pond SL (2010) Datamonkey 2010: a suite of phylogenetic analysis tools for evolutionary biology. Bioinformatics 26(19):2455–2457

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • DeRossi C, Bambino K, Morrison J, Sakarin I, Villacorta-Martin C, Zhang C, Ellis JL, Fiel MI, Ybanez M, Lee YA et al (2019) Mannose phosphate isomerase and mannose regulate hepatic stellate cell activation and fibrosis in zebrafish and humans. Hepatology 70(6):2107–2122

    Article  CAS  PubMed  Google Scholar 

  • Finsterer J (2019) Congenital myasthenic syndromes. Orphanet J Rare Dis 14(1):57–79

    Article  PubMed  PubMed Central  Google Scholar 

  • Gélinas R, Mailleux F, Dontaine J, Bultot L, Demeulder B, Ginion A, Daskalopoulos EP, Esfahani H, Dubois-Deruy E, Lauzier B et al (2018) AMPK activation counteracts cardiac hypertrophy by reducing O-GlcNAcylation. Nat Commun 9(1):374–391

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Harrison GF, Sanz J, Boulais J, Mina MJ, Grenier JC, Leng Y, Dumaine A, Yotova V, Bergey CM, Nsobya SL et al (2019) Natural selection contributed to immunological differences between hunter-gatherers and agriculturalists. Nat Ecol Evol 3(8):1253–1264

    Article  PubMed  PubMed Central  Google Scholar 

  • Helman G, Sharma S, Crawford J, Patra B, Jain P, Bent SJ, Urtizberea JA, Saran RK, Taft RJ, Knaap MS et al (2019) Leukoencephalopathy due to variants in associated congenital myasthenic syndrome. Neurology 92(6):e587–e593

    Article  CAS  PubMed  Google Scholar 

  • Holland ND, Chen J (2001) Origin and early evolution of the vertebrates: new insights from advances in molecular biology, anatomy, and palaeontology. BioEssays 23(2):142–151

    Article  CAS  PubMed  Google Scholar 

  • Irie N, Kuratani S (2011) Comparative transcriptome analysis reveals vertebrate phylotypic period during organogenesis. Nat Commun 2(1):248–254

    Article  PubMed  CAS  Google Scholar 

  • Irie N, Kuratani S (2014) The developmental hourglass model: a predictor of the basic body plan? Development 141(24):4649–4655

    Article  CAS  PubMed  Google Scholar 

  • Issop Y, Hathazi D, Khan MM, Rudolf R, Weis J, Spendiff S, Slater CR, Roos A, Lochmüller H (2018) GFPT1 deficiency in muscle leads to myasthenia and myopathy in mice. Hum Mol Genet 27(18):3218–3232

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Juven-Gershon T, Hsu JY, Kadonaga JT (2008) Caudal, a key developmental regulator, is a DPE-specific transcriptional factor. Genes Dev 22(20):2823–2830

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kaushik AK, Shojaie A, Panzitt K, Sonavane R, Venghatakrishnan H, Manikkam M, Zaslavsky A, Putluri V, Vasu VT, Zhang Y et al (2016) Inhibition of the hexosamine biosynthetic pathway promotes castration-resistant prostate cancer. Nat Commun 7:11612–11629

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kirschman LJ, McCue MD, Boyles JG, Warne RW (2017) Exogenous stress hormones alter energetic and nutrient costs of development and metamorphosis. J Exp Biol 220(Pt 18):3391–3397

    PubMed  Google Scholar 

  • Kumar S, Sanderford M, Gray VE, Ye J, Liu L (2012) Evolutionary diagnosis method for variants in personal exomes. Nat Methods 9(9):855–856

    Article  CAS  PubMed  Google Scholar 

  • Kumar S, Stecher G, Li M, Knyaz C, Tamura K (2018) MEGA X: molecular evolutionary genetics analysis across computing platforms. Mol Biol Evol 35(6):1547–1549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lam C, Low JY, Tran PT, Wang H (2021) The hexosamine biosynthetic pathway and cancer: current knowledge and future therapeutic strategies. Cancer Lett 503:11–18

    Article  CAS  PubMed  Google Scholar 

  • Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R et al (2007) Clustal W and Clustal X version 2.0. Bioinformatics 23(21):2947–2948

    Article  CAS  PubMed  Google Scholar 

  • Letunic I, Khedkar S, Bork P (2021) SMART: recent updates, new developments and status in 2020. Nucleic Acids Res 49(D1):d458–d460

    Article  CAS  PubMed  Google Scholar 

  • Li T, Zhang Z, Kolwicz SC Jr, Abell L, Roe ND, Kim M, Zhou B, Cao Y, Ritterhoff J, Gu H et al (2017) Defective branched-chain amino acid catabolism disrupts glucose metabolism and sensitizes the heart to ischemia-reperfusion injury. Cell Metab 25(2):374–385

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Martinez-Gutierrez CA, Aylward FO (2019) Strong purifying selection is associated with genome streamlining in epipelagic marinimicrobia. Genome Biol Evol 11(10):2887–2894

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moloughney JG, Kim PK, Vega-Cotto NM, Wu CC, Zhang S (2016) mTORC2 responds to glutamine catabolite levels to modulate the hexosamine biosynthesis enzyme GFAT1. Mol Cell 63(5):811–826

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Murrell B, Wertheim JO, Moola S, Weighill T, Scheffler K, Pond SLK (2012) Detecting individual sites subject to episodic diversifying selection. PLoS Genet 8(7):e1002764 (e1002774)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nicholas KB, Nicholas H (1997) GeneDoc: a tool for editing and annotating multiple sequence alignments. Distributed by the authors 4. http://www.cris.com/ketchup/genedoc.shtml. Accessed 29 Feb 2020

  • Nie H, Yi W (2019) O-GlcNAcylation, a sweet link to the pathology of diseases. J Zhejiang Univ Sci B 20(5):437–448

    Article  PubMed  PubMed Central  Google Scholar 

  • Pond SLK, Frost SDW (2005) Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22(5):1208–1222

    Article  CAS  Google Scholar 

  • Pond SL, Frost SD, Grossman Z, Gravenor MB, Richman DD, Brown AJ (2006) Adaptation to different human populations by HIV-1 revealed by codon-based analyses. PLoS Comput Biol 2(6):e62–e72

    Article  PubMed  CAS  Google Scholar 

  • Pond SL, Scheffler K, Gravenor MB, Poon AF, Frost SD (2010) Evolutionary fingerprinting of genes. Mol Biol Evol 27(3):520–536

    Article  PubMed  CAS  Google Scholar 

  • Prisco SZ, Rose L, Potus F, Tian L, Wu D, Hartweck L, Al-Qazazi R, Neuber-Hess M, Eklund M, Hsu S et al (2020) Excess protein O-GlcNAcylation links metabolic derangements to right ventricular dysfunction in pulmonary arterial hypertension. Int J Mol Sci. 21(19):7278–7296

    Article  CAS  PubMed Central  Google Scholar 

  • R Core Team (2018) R: a language and environment for statistical computing. R Foundation for Statistical Computing. http://www.r-project.org/. Accessed 29 Feb 2020

  • Sayeski PP, Paterson AJ, Kudlow JE (1994) The murine glutamine:fructose-6-phosphate amidotransferase-encoding cDNA sequence. Gene 140(2):289–290

    Article  CAS  PubMed  Google Scholar 

  • Semmelmann F, Hupfeld E, Heizinger L, Merkl R, Sterner R (2019) A fold-independent interface residue is crucial for complex formation and allosteric signaling in class I glutamine amidotransferases. Biochemistry 58(22):2584–2588

    Article  CAS  PubMed  Google Scholar 

  • Shimizu M, Tanaka N (2019) IL-8-induced O-GlcNAc modification via GLUT3 and GFAT regulates cancer stem cell-like properties in colon and lung cancer cells. Oncogene 38(9):1520–1533

    Article  CAS  PubMed  Google Scholar 

  • Shir-Shapira H, Sharabany J, Filderman M, Ideses D, Ovadia-Shochat A, Mannervik M, Juven-Gershon T (2015) Structure-function analysis of the drosophila melanogaster caudal transcription factor provides insights into core promoter-preferential activation. J Biol Chem 290(28):17293–17305

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Srinivasan V, Sandhya N, Sampathkumar R, Farooq S, Mohan V, Balasubramanyam M (2007) Glutamine fructose-6-phosphate amidotransferase (GFAT) gene expression and activity in patients with type 2 diabetes: inter-relationships with hyperglycaemia and oxidative stress. Clin Biochem 40(13–14):952–957

    Article  CAS  PubMed  Google Scholar 

  • Stanislauskienė R, Laurynėnas A, Rutkienė R, Aučynaitė A, Tauraitė D, Meškienė R, Urbelienė N, Kaupinis A, Valius M, Kaliniene L et al (2020) YqfB protein from Escherichia coli: an atypical amidohydrolase active towards N(4)-acylcytosine derivatives. Sci Rep 10(1):788–800

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Szklarczyk D, Gable AL, Lyon D, Junge A, Wyder S, Huerta-Cepas J, Simonovic M, Doncheva NT, Morris JH, Bork P et al (2019) STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Res 47(D1):D607-d613

    Article  CAS  PubMed  Google Scholar 

  • Tran DH, May HI, Li Q, Luo X, Huang J, Zhang G, Niewold E, Wang X, Gillette TG, Deng Y et al (2020) Chronic activation of hexosamine biosynthesis in the heart triggers pathological cardiac remodeling. Nat Commun 11(1):1771–1788

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Very N, Vercoutter-Edouart AS, Lefebvre T, Hardivillé S, El Yazidi-Belkoura I (2018) Cross-dysregulation of O-GlcNAcylation and PI3K/AKT/mTOR axis in human chronic diseases. Front Endocrinol 9:602–612

    Article  Google Scholar 

  • WCB, McGraw-Hill KJ (2014) Vertebrates: comparative anatomy, function, evolution. Syst Biol 9(2):250–251

    Google Scholar 

  • Whitmore TE, Mudri SL, McKnight GL (1995) Physical mapping of the human glutamine: fructose-6-phosphate amidotransferase gene (GFPT) to chromosome 2p13. Genomics 26:422–423

    Article  CAS  PubMed  Google Scholar 

  • York JR, McCauley DW (2020) The origin and evolution of vertebrate neural crest cells. Open Biol 10(1):190285–190295

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang H, Jia Y, Cooper JJ, Hale T, Zhang Z, Elbein SC (2004) Common variants in glutamine:fructose-6-phosphate amidotransferase 2 (GFPT2) gene are associated with type 2 diabetes, diabetic nephropathy, and increased GFPT2 mRNA levels. J Clin Endocrinol Metab 89(2):748–755

    Article  CAS  PubMed  Google Scholar 

  • Zhang X, Yu K, Ma L, Qian Z, Tian X, Miao Y, Niu Y, Xu X, Guo S, Yang Y et al (2021) Endogenous glutamate determines ferroptosis sensitivity via ADCY10-dependent YAP suppression in lung adenocarcinoma. Theranostics 11(12):5650–5674

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao M, Li H, Ma Y, Gong H, Yang S, Fang Q, Hu Z (2017) Nanoparticle abraxane possesses impaired proliferation in A549 cells due to the underexpression of glucosamine 6-phosphate N-acetyltransferase 1 (GNPNAT1/GNA1). Int J Nanomed 12:1685–1697

    Article  CAS  Google Scholar 

  • Zibrova D, Vandermoere F, Göransson O, Peggie M, Mariño KV, Knierim A, Spengler K, Weigert C, Viollet B, Morrice NA et al (2017) GFAT1 phosphorylation by AMPK promotes VEGF-induced angiogenesis. Biochem J 474(6):983–1001

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

We are grateful to the experts who participated in the review of this article. This study was financially supported by grants from the National Natural Science foundation of China (No. 81900245and 81700256).

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  1. Si-ang Wei and Ran Xu: co-first author.

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  1. Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, 180 Feng Lin Road, Shanghai, 200032, People’s Republic of China

    Si-ang Wei, Ran Xu, Yu-yao Ji, Zhi-wen Ding & Yun-zeng Zou

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Contributions

WSA, DZW conceived and designed the experiments. WSA, XR, JYY, performed the experiments. WSA, DZW, ZYZ analyzed the data and wrote the manuscript. All the authors reviewed the manuscript.

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Correspondence to Zhi-wen Ding or Yun-zeng Zou.

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WSA, XR, JYY, DZW and ZYZ declare that they have no conflict of interest.

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Wei, Sa., Xu, R., Ji, Yy. et al. Deduction and exploration of the evolution and function of vertebrate GFPT family. Genes Genom 44, 175–185 (2022). https://doi.org/10.1007/s13258-021-01188-8

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