, Volume 60, Issue 7, pp 383–397 | Cite as

Comprehensive clarification of two paralogous interleukin 4/13 loci in teleost fish

  • Maki Ohtani
  • Nobuhiro Hayashi
  • Keiichiro Hashimoto
  • Teruyuki Nakanishi
  • Johannes Martinus DijkstraEmail author
Original Paper


Interleukins 4 and 13 (IL-4 and IL-13) are related cytokines important for Th2 immune responses and encoded by adjacent genes on human chromosome 5. Efforts were made previously to detect these genes in fish, but research was hampered by a lack of sequence conservation. A Tetraodon nigrovirides (green spotted pufferfish) gene was annotated as IL-4 by Li et al. (Mol Immunol, 44:2078–2086, 2007), but this annotation was not well substantiated. However, the present study concludes that the reported pufferfish gene belongs to the IL-4/13 lineage indeed, while also describing an additional IL-4/13 copy in a paralogous genomic region. Our analyses of IL-4/13 loci in fish describe (1) genomic region history, (2) characteristic intron–exon organization, (3) deduced IL-4/13 molecules for several teleost fish species, (4) IL-4/13 lineage-specific protein motifs including a cysteine pair (pair 1), and (5) computer software predictions of a type I cytokine fold. Teleost IL-4/13 molecules have an additional cysteine pair (pair 2) or remnants thereof, which is absent in mammalian IL-4 and IL-13. We were unable to determine if the teleost IL-4/13 genes are orthologous to either IL-4 or IL-13, or if these mammalian genes separated later in evolution.


Interleukin 4 Interleukin 13 Cytokines Evolution Fish Genome duplication 



This work was supported by Grants-in-Aid for Scientific Research categories (B) and (C) to TN (18380120) and JMD (19580220), respectively, from the Japan Society for the Promotion of Science (JSPS).

Supplementary material

251_2008_299_MOESM1_ESM.pdf (77 kb)
Supplementary Fig. 1 Phylogenetic tree analyses by neighbor-joining method for HSPA4 (a), FGF1 (c), and KCTD16 (e) and related molecules. Trees were based on alignments of conserved fragments (b, d, f). GenBank accession numbers and/or Ensembl database-derived chromosome positions are indicated. The reliabilities of the cluster analyses are tested by bootstrap confidence limits and indicated as percent success per 1,000 bootstrap trials with values in red font on nodes. Genetic distances are indicated with black font (PDF 79 KB)
251_2008_299_MOESM2_ESM.pdf (13 kb)
Supplementary Fig. 2 Alignment of Tetraodon and Fugu IL-4/13B genomic sequences. Amino acids of the Tetraodon sequence are listed above first nucleotides of codons. GATA-3 binding motifs are boxed. Red, open reading frames; green, mRNA destabilization motif; purple, poly-adenylation motif (PDF 13 KB)
251_2008_299_MOESM3_ESM.pdf (9 kb)
Supplementary Fig. 3 Promoter regions of stickleback IL-4/13A, medaka IL-4/13A2, and zebrafish IL-4/13A. Amino acids are listed above first nucleotides of codons. TATA boxes and GATA-3 binding motifs are boxed. Red, open reading frames (PDF 9 KB)
251_2008_299_MOESM4_ESM.pdf (9 kb)
Supplementary Fig. 4 Aligment of zebrafish IL-4/13A and human IL-13 used for 3D modeling. α-Helices indicated by 3D-PSSM software are colored (PDF 9 KB).
251_2008_299_MOESM5_ESM.xls (70 kb)
Supplementary Table 1 Topmatches of huCr4-, huChr5-, and huChrX-encoded protein fragments with sequences in Ensembl databases (tblastn analysis against the whole genome). Chromosomes with C1 identities listed in Fig. 1 are indicated with solid pink boxes, and other chromosomes with major C1 identities but not shown in Fig. 1 are indicated by pink striped boxes. Chromosomes with C2 but no C1 identities listed in Fig. 1 are indicated with solid blue boxes. Mostly, the four top matches are shown, but if considered interesting, more matches are shown; some protein fragments had less than four significant matches. The numbers following the chromosomes indicate the positions at the assembled chromosome sequences in megabases. For the matches with scaffolds not assigned to chromosomes, positions are not indicated (XLS 71 KB)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2008

Authors and Affiliations

  • Maki Ohtani
    • 1
  • Nobuhiro Hayashi
    • 2
  • Keiichiro Hashimoto
    • 2
  • Teruyuki Nakanishi
    • 1
  • Johannes Martinus Dijkstra
    • 2
    Email author
  1. 1.Laboratory of Fish Pathology, Department of Veterinary MedicineNihon UniversityFujisawaJapan
  2. 2.Institute for Comprehensive Medical ScienceFujita Health UniversityToyoakeJapan

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