Marine Biotechnology

, Volume 20, Issue 5, pp 603–610 | Cite as

The FTO Gene Is Associated with Growth and Omega-3/-6 Ratio in Asian Seabass

  • Fei Sun
  • Rongjian Tu
  • Jun Hong Xia
  • Xiao Jun Liu
  • Gen Hua Yue
Original Article


Polymorphisms in the FTO gene are associated with obesity and body mass index in humans and livestock. Little information of whether FTO plays an important role in aquaculture fish species is available. We cloned and characterized the FTO gene in an economically important food fish species: Asian seabass (Lates calcarifer). The full-length cDNA of the gene is 3679 bp, containing an ORF of 1935 bp encoding 644 amino acids, a 216 bp 5′ UTR and a 1538 bp 3′ UTR. The gene consisted of nine exons and eight introns and was 117,679 bp in length. Phylogenetic analysis revealed that the gene in Asian seabass was closely related to those of Japanese flounder and Nile tilapia. Analysis of its expressions using qRT-PCR showed that it was expressed ubiquitously, but was higher in the liver, stomach and intestine. Comparative analysis of the genomic sequences of part of intron 1 of the gene among 10 unrelated individuals identified two SNPs. Analysis of associations between SNPs and traits (i.e. growth, oil content, omega-3 and -6 contents) in an F2 family demonstrated that the two SNPs were significantly associated with growth, oil content, omega-3 content and omega-3/-6 ratio. Altogether, our data suggest that the gene or/and its linked genes play an important role in growth and fatty acid synthesis, and that the SNPs associated with traits may be used as markers for selecting quicker growth and higher omega-3/-6 ratio at the fingerling stage.


FTO Polymorphism Trait Breeding Aquaculture 



We thank our colleagues Zi Yi Wan, Hong Yan Pang, Yan Fei Wen and Bing Liang for supplying technical support for this work, and Baoqing Ye for editing the English of this manuscript.

Funding Information

This research was supported by the National Research Foundation, Prime Minister’s Office, Singapore, under its Competitive Research Program (CRP Award No. NRF-CRP7-2010-01) and the internal fund of Temasek Life Sciences Laboratory, Singapore.

Compliance with Ethical Standards

All handling of fish was conducted in accordance with the guidelines on the care and use of animals for scientific purposes set up by the Institutional Animal Care and Use Committee (IACUC) of the Temasek Life Sciences Laboratory, Singapore. The IACUC has specially approved this study within the project “Breeding of Asian seabass” (approval number is TLL (F)-12-004).

Conflict of Interest

The authors declare that they have no competing interests.

Supplementary material

10126_2018_9831_MOESM1_ESM.jpg (770 kb)
Supplementary Figure 1 Genomic organization of FTO and its neighbouring genes (not drawn to scale) in Asian seabass and humans. In Asian seabass, the FTO gene contains nine exons, which are depicted in blue rectangles, and two SNPs (i.e., SNP1 and 2) are located in intron 1 of the gene. In humans, the FTO gene contains nine exons which are depicted in blue rectangles, and the SNP rs9939609 is found in intron 1 of the gene. (JPG 770 kb)
10126_2018_9831_MOESM2_ESM.jpg (6.4 mb)
Supplementary Figure 2 Conserved and variable regions of the FTO gene in 14 species. (JPG 6561 kb)
10126_2018_9831_MOESM3_ESM.jpg (2.9 mb)
Supplementary Figure 3 Two SNPs (SNP1 and SNP2) detected in intron 1 of the FTO gene and their flanking sequences in Asian seabass. (JPG 2984 kb)
10126_2018_9831_MOESM4_ESM.docx (16 kb)
Supplementary Table 1 Primers used for cloning and characterizing the FTO gene in Asian seabass (DOCX 15 kb)


  1. Cheung M-KM, Yeo GS (2011) FTO biology and obesity: why do a billion of us weigh 3 kg more? Front Endocrinol 2:4CrossRefGoogle Scholar
  2. Church C, Moir L, Mcmurray F, Girard C, Banks GT, Teboul L, Wells S, Bruning JC et al (2010) Overexpression of Fto leads to increased food intake and results in obesity. Nat Genet 42:1086–U147CrossRefPubMedPubMedCentralGoogle Scholar
  3. Domingos JA, Zenger KR, Jerry DR (2015) Whole genome shotgun sequence assembly enables rapid gene characterization in the tropical fish barramundi, Lates calcarifer. Anim Genet 46:468–469CrossRefPubMedGoogle Scholar
  4. Du ZQ, Fan B, Zhao X, Amoako R, Rothschild MF (2009) Association analyses between type 2 diabetes genes and obesity traits in pigs. Obesity 17:323–329CrossRefPubMedGoogle Scholar
  5. Fan B, Du Z-Q, Rothschild MF (2009) The fat mass and obesity-associated (FTO) gene is associated with intramuscular fat content and growth rate in the pig. Anim Biotechnol 20:58–70CrossRefPubMedGoogle Scholar
  6. Fan B, Lkhagvadorj S, Cai W, Young J, Smith R, Dekkers J, Huff-Lonergan E, Lonergan S et al (2010) Identification of genetic markers associated with residual feed intake and meat quality traits in the pig. Meat Sci 84:645–650CrossRefPubMedGoogle Scholar
  7. Fischer J, Koch L, Emmerling C, Vierkotten J, Peters T, Brüning JC, Rüther U (2009) Inactivation of the Fto gene protects from obesity. Nature 458:894–898CrossRefPubMedGoogle Scholar
  8. Frayling TM, Timpson NJ, Weedon MN, Zeggini E, Freathy RM, Lindgren CM, Perry JRB, Elliott KS, Lango H, Rayner NW, Shields B, Harries LW, Barrett JC, Ellard S, Groves CJ, Knight B, Patch AM, Ness AR, Ebrahim S, Lawlor DA, Ring SM, Ben-Shlomo Y, Jarvelin MR, Sovio U, Bennett AJ, Melzer D, Ferrucci L, Loos RJF, Barroso I, Wareham NJ, Karpe F, Owen KR, Cardon LR, Walker M, Hitman GA, Palmer CNA, Doney ASF, Morris AD, Smith GD, The Wellcome Trust Case Control Consortium, Hattersley AT, McCarthy MI (2007) A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 316:889–894CrossRefPubMedPubMedCentralGoogle Scholar
  9. Fredriksson R, HäGglund M, Olszewski PK, Stephansson O, Jacobsson JA, Olszewska AM, Levine AS, Lindblom J et al (2008) The obesity gene, FTO, is of ancient origin, up-regulated during food deprivation and expressed in neurons of feeding-related nuclei of the brain. Endocrinology 149:2062–2071CrossRefPubMedGoogle Scholar
  10. Fu Y, Jia G, Pang X, Wang RN, Wang X, Li CJ, Smemo S, Dai Q et al (2013a) FTO-mediated formation of N6-hydroxymethyladenosine and N6-formyladenosine in mammalian RNA. Nat Commun 4:1798CrossRefPubMedPubMedCentralGoogle Scholar
  11. Fu Y, Li L, Ren S (2013b) Effect of FTO expression and polymorphism on fat deposition in Suzhong pigs. Asian Australas J Anim Sci 26:1365CrossRefPubMedPubMedCentralGoogle Scholar
  12. Gan W, Song Q, Zhang N, Xiong X, Wang D, Li L (2015) Association between FTO polymorphism in exon 3 with carcass and meat quality traits in crossbred ducks. Genet Mol Res 14:6699–6714CrossRefPubMedGoogle Scholar
  13. Geng X, Liu SK, Yuan ZH, Jiang YL, Zhi DG, Liu ZJ (2017) A genome-wide association study reveals that genes with functions for bone development are associated with body conformation in catfish. Mar Biotechnol 19:570–578CrossRefPubMedGoogle Scholar
  14. Gerken T, Girard CA, Tung YCL, Webby CJ, Saudek V, Hewitson KS, Yeo GSH, Mcdonough MA et al (2007) The obesity-associated FTO gene encodes a 2-oxoglutarate-dependent nucleic acid demethylase. Science 318:1469–1472CrossRefPubMedPubMedCentralGoogle Scholar
  15. Jerry DR (2013) Biology and culture of Asian seabass Lates calcarifer. CRC PressGoogle Scholar
  16. Kumar S, Tamura K, Jakobsen IB, Nei M (2001) MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244–1245CrossRefPubMedGoogle Scholar
  17. Li HL, Gu XH, Li BJ, Chen CH, Lin HR, Xia JH (2017a) Genome-wide QTL analysis identified significant associations between hypoxia tolerance and mutations in the GPR132 and ABCG4 genes in Nile tilapia. Mar Biotechnol 19:441–453CrossRefPubMedGoogle Scholar
  18. Li HL, Lin HR, Xia JH (2017b) Differential gene expression profiles and alternative isoform regulations in gill of Nile tilapia in response to acute hypoxia. Mar Biotechnol 19:551–562CrossRefPubMedGoogle Scholar
  19. Lin G, Wang L, Te Ngoh S, Ji L, Orbán L, Yue GH (2018) Mapping QTL for omega-3 content in hybrid saline tilapia. Mar Biotechnol 21:10–19CrossRefGoogle Scholar
  20. Liu P, Wang L, Wan ZY, Ye BQ, Huang S, Wong S-M, Yue GH (2016) Mapping QTL for resistance against viral nervous necrosis disease in Asian seabass. Mar Biotechnol 18:107–116CrossRefPubMedGoogle Scholar
  21. Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCT method. Methods 25:402–408CrossRefPubMedGoogle Scholar
  22. Meyer A, Van De Peer Y (2005) From 2R to 3R: evidence for a fish-specific genome duplication (FSGD). BioEssays 27:937–945CrossRefPubMedGoogle Scholar
  23. O’fallon J, Busboom J, Nelson M, Gaskins C (2007) A direct method for fatty acid methyl ester synthesis: application to wet meat tissues, oils, and feedstuffs. J Anim Sci 85:1511–1521CrossRefPubMedGoogle Scholar
  24. Rask-Andersen M, Almén MS, Schiöth HB (2015) Scrutinizing the FTO locus: compelling evidence for a complex, long-range regulatory context. Hum Genet 134:1183–1193CrossRefPubMedGoogle Scholar
  25. Reitz C, Tosto G, Mayeux R, Luchsinger JA (2012) Genetic variants in the fat and obesity associated (FTO) gene and risk of Alzheimer’s disease. PLoS One 7:e50354CrossRefPubMedPubMedCentralGoogle Scholar
  26. Robbens S, Rouzé P, Cock JM, Spring J, Worden AZ, Van De Peer Y (2008) The FTO gene, implicated in human obesity, is found only in vertebrates and marine algae. J Mol Evol 66:80–84CrossRefPubMedGoogle Scholar
  27. Simopoulos AP (2002) The importance of the ratio of omega-6/omega-3 essential fatty acids. Biomed Pharmacother 56:365–379CrossRefPubMedGoogle Scholar
  28. Smemo S, Tena JJ, Kim K-H, Gamazon ER, Sakabe NJ, Gómez-Marín C, Aneas I, Credidio FL, Sobreira DR, Wasserman NF, Lee JH, Puviindran V, Tam D, Shen M, Son JE, Vakili NA, Sung HK, Naranjo S, Acemel RD, Manzanares M, Nagy A, Cox NJ, Hui CC, Gomez-Skarmeta JL, Nóbrega MA (2014) Obesity-associated variants within FTO form long-range functional connections with IRX3. Nature 507:371–375CrossRefPubMedPubMedCentralGoogle Scholar
  29. Stratigopoulos G, Carli JFM, O’day DR, Wang L, Leduc CA, Lanzano P, Chung WK, Rosenbaum M et al (2014) Hypomorphism for RPGRIP1L, a ciliary gene vicinal to the FTO locus, causes increased adiposity in mice. Cell Metab 19:767–779CrossRefPubMedPubMedCentralGoogle Scholar
  30. Vij S, Kuhl H, Kuznetsova IS, Komissarov A, Yurchenko AA, Van Heusden P, Singh S, Thevasagayam NM et al (2016) Chromosomal-level assembly of the Asian seabass genome using long sequence reads and multi-layered scaffolding. PLoS Genet 12:e1005954CrossRefPubMedPubMedCentralGoogle Scholar
  31. Wang C, Lo L, Feng F, Zhu Z, Yue G (2008a) Identification and verification of QTL associated with growth traits in two genetic backgrounds of Barramundi (Lates calcarifer). Anim Genet 39:34–39CrossRefPubMedGoogle Scholar
  32. Wang CM, Lo LC, Feng F, Gong P, Li J, Zhu ZY, Lin G, Yue GH (2008b) Construction of a BAC library and mapping BAC clones to the linkage map of Barramundi, Lates calcarifer. BMC Genomics 9:139CrossRefPubMedPubMedCentralGoogle Scholar
  33. Wang CM, Lo LC, Zhu ZY, Lin G, Feng F, Li J, Yang WT, Tan J et al (2008c) Estimating reproductive success of brooders and heritability of growth traits in Asian sea bass (Lates calcarifer) using microsatellites. Aquac Res 39:1612–1619Google Scholar
  34. Wang CM, Zhu ZY, Lo LC, Feng F, Lin G, Yang WT, Li J, Yue GH (2007) A microsatellite linkage map of Barramundi, Lates calcarifer. Genetics 175:907–915CrossRefPubMedPubMedCentralGoogle Scholar
  35. Wang L, Bai B, Huang S, Liu P, Wan ZY, Ye B, Wu J, Yue GH (2017a) QTL mapping for resistance to iridovirus in Asian seabass using genotyping-by-sequencing. Mar Biotechnol 19:517–527CrossRefPubMedGoogle Scholar
  36. Wang L, Bai B, Liu P, Huang SQ, Wan ZY, Chua E, Ye B, Yue GH (2017b) Construction of high-resolution recombination maps in Asian seabass. BMC Genomics 18:63CrossRefPubMedPubMedCentralGoogle Scholar
  37. Wang L, Wan ZY, Bai B, Huang SQ, Chua E, Lee M, Pang HY, Wen YF, Liu P, Liu F, Sun F, Lin G, Ye BQ, Yue GH (2015) Construction of a high-density linkage map and fine mapping of QTL for growth in Asian seabass. Sci Rep 5:16358CrossRefPubMedPubMedCentralGoogle Scholar
  38. Xia JH, Feng F, Lin G, Wang CM, Yue GH (2010) A first generation BAC-based physical map of the Asian seabass (Lates calcarifer). PLoS One 5:e11974CrossRefPubMedPubMedCentralGoogle Scholar
  39. Xia JH, Lin G, He X, Yunping B, Liu P, Liu F, Sun F, Tu R, Yue GH (2014) Mapping quantitative trait loci for omega-3 fatty acids in Asian seabass. Mar Biotechnol 16:1–9CrossRefPubMedGoogle Scholar
  40. Xia JH, Liu P, Liu F, Lin G, Sun F, Tu R, Yue GH (2013) Analysis of stress-responsive transcriptome in the intestine of Asian seabass (Lates calcarifer) using RNA-Seq. DNA Res 20:449–460CrossRefPubMedPubMedCentralGoogle Scholar
  41. Xia JH, Yue GH (2010) Identification and analysis of immune-related transcriptome in Asian seabass Lates calcarifer. BMC Genomics 11:356CrossRefPubMedPubMedCentralGoogle Scholar
  42. Ye B, Wan Z, Wang L, Pang H, Wen Y, Liu H, Liang B, Lim HS, Jiang J, Yue G (2017) Heritability of growth traits in the Asian seabass (Lates calcarifer). Aquacul Fish 2:112–118CrossRefGoogle Scholar
  43. Yue G, Li Y, Chao T, Chou R, Orban L (2002) Novel microsatellites from Asian sea bass (Lates calcarifer) and their application to broodstock analysis. Mar Biotechnol 4:503–511CrossRefPubMedGoogle Scholar
  44. Yue G, Orban L, Lim H (2017) Current status of the Asian seabass breeding program. Aquaculture 472:85–85Google Scholar
  45. Yue GH (2014) Recent advances of genome mapping and marker-assisted selection in aquaculture. Fish Fish 15:376–396CrossRefGoogle Scholar
  46. Yue GH, Zhu ZY, Lo LC, Wang CM, Lin G, Fenf F, Pang HY, Li J et al (2009) Genetic variation and population structure of Asian seabass (Lates calcarifer) in the Asia-Pacific region. Aquaculture 293:22–28CrossRefGoogle Scholar
  47. Zhang G-W, Gao L, Chen S-Y, Zhao X-B, Tian Y-F, Wang X, Deng X-S, Lai S-J (2013) Single nucleotide polymorphisms in the FTO gene and their association with growth and meat quality traits in rabbits. Gene 527:553–557CrossRefPubMedGoogle Scholar
  48. Zhao L, Li YP, Li YJ, Yu JC, Liao H, Wang SY, Lv J, Liang J et al (2017) A genome-wide association study identifies the genomic region associated with shell color in yesso scallop, Patinopecten yessoensis. Mar Biotechnol 19:301–309CrossRefPubMedGoogle Scholar
  49. Zhu ZY, Lin G, Lo LC, Xu YX, Feng F, Chou R, Yue GH (2006) Genetic analyses of Asian seabass stocks using novel polymorphic microsatellites. Aquaculture 256:167–173CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Fei Sun
    • 1
  • Rongjian Tu
    • 1
    • 2
  • Jun Hong Xia
    • 1
    • 3
  • Xiao Jun Liu
    • 1
    • 4
  • Gen Hua Yue
    • 1
    • 5
    • 6
  1. 1.Temasek Life Sciences LaboratoryNational University of SingaporeSingaporeSingapore
  2. 2.Institute of Crop Breeding and CultivationShanghai Academy of Agricultural SciencesShanghaiChina
  3. 3.State Key Laboratory of Biocontrol, Institute of Aquatic Economic Animals and Guangdong Provincial Key Laboratory for Aquatic Economic Animals, College of Life SciencesSun Yat-Sen UniversityGuangzhouPeople’s Republic of China
  4. 4.Key Laboratory of Exploration and Utilization of Aquatic Genetic Resources, Shanghai Ocean University, Ministry of EducationShanghai Ocean UniversityShanghaiChina
  5. 5.Department of Biological SciencesNational University of SingaporeSingaporeSingapore
  6. 6.School of Biological SciencesNanyang Technological UniversitySingaporeSingapore

Personalised recommendations