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Intraclass diversification of immunoglobulin heavy chain genes in the African lungfish

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Abstract

Lungfish (Dipnoi) are the closest living relatives to tetrapods, and they represent the transition from water to land during vertebrate evolution. Lungfish are armed with immunoglobulins (Igs), one of the hallmarks of the adaptive immune system of jawed vertebrates, but only three Ig forms have been characterized in Dipnoi to date. We report here a new diversity of Ig molecules in two African lungfish species (Protopterus dolloi and Protopterus annectens). The African lungfish Igs consist of three IgMs, two IgWs, three IgNs, and an IgQ, where both IgN and IgQ originated evidently from the IgW lineage. Our data also suggest that the IgH genes in the lungfish are organized in a transiting form from clusters (IgH loci in cartilaginous fish) to a translocon configuration (IgH locus in tetrapods). We propose that the intraclass diversification of the two primordial gnathostome Ig classes (IgM and IgW) as well as acquisition of new isotypes (IgN and IgQ) has allowed lungfish to acquire a complex and functionally diverse Ig repertoire to fight a variety of microorganisms. Furthermore, our results support the idea that “tetrapod-specific” Ig classes did not evolve until the vertebrate adaptation to land was completed ~360 million years ago.

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References

  • Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410

    Article  PubMed  CAS  Google Scholar 

  • Amemiya CT, Alföldi J, Lee AP, Fan S, Philippe H, MacCallum I, Braasch I, Manousaki T, Schneider I, Rohner N (2013) The African coelacanth genome provides insights into tetrapod evolution. Nature 496:311–316

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Brinkmann H, Venkatesh B, Brenner S, Meyer A (2004) Nuclear protein-coding genes support lungfish and not the coelacanth as the closest living relatives of land vertebrates. Proc Natl Acad Sci 101:4900–4905

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Campanella JJ, Bitincka L, Smalley J (2003) MatGAT: an application that generates similarity/identity matrices using protein or DNA sequences. BMC Bioinforma 4:29

    Article  Google Scholar 

  • Chartrand S, Litman G, Lapointe N, Good R, Frommel D (1971) The evolution of the immune response XII. The immunoglobulins of the turtle. Molecular requirements for biologic activity of 5.7 S immunoglobulin. J Immunol 107:1–11

    PubMed  CAS  Google Scholar 

  • Chen K, Cerutti A (2010) Vaccination strategies to promote mucosal antibody responses. Immunity 33:479–491

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Cheng G, Gao Y, Wang T, Sun Y, Wei Z, Li L, Ren L, Guo Y, Hu X, Lu Y (2013) Extensive diversification of IgH subclass-encoding genes and IgM subclass switching in crocodilians. Nat Commun 4:1337

    Article  PubMed  CAS  Google Scholar 

  • Chenna R, Sugawara H, Koike T, Lopez R, Gibson TJ, Higgins DG, Thompson JD (2003) Multiple sequence alignment with the Clustal series of programs. Nucleic Acids Res 31:3497–3500

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Edholm E-S, Bengten E, Wilson M (2011) Insights into the function of IgD. Dev Comp Immunol 35:1309–1316

    Article  PubMed  CAS  Google Scholar 

  • Flajnik MF (2002) Comparative analyses of immunoglobulin genes: surprises and portents. Nat Rev Immunol 2:688–698

    Article  PubMed  CAS  Google Scholar 

  • Gregory TR (2005) Genome size evolution in animals. In The evolution of the genome 1:4–87

  • Gregory TR (2009) Macroevolution, hierarchy theory, and the C-value enigma

  • Hallström BM, Janke A (2009) Gnathostome phylogenomics utilizing lungfish EST sequences. Mol Biol Evol 26:463–471

    Article  PubMed  CAS  Google Scholar 

  • Hordvik I (1998) The impact of ancestral tetraploidy on antibody heterogeneity in salmonid fishes. Immunol Rev 166:153–157

    Article  PubMed  CAS  Google Scholar 

  • Lee V, Huang JL, Lui MF, Malecek K, Ohta Y, Mooers A, Hsu E (2008) The evolution of multiple isotypic IgM heavy chain genes in the shark. J Immunol 180:7461–7470

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Leggatt RA, Iwama GK (2003) Occurrence of polyploidy in the fishes. Rev Fish Biol Fish 13:237–246

    Article  Google Scholar 

  • Liang D, Shen XX, Zhang P (2013) One thousand two hundred ninety nuclear genes from a genome-wide survey support lungfishes as the sister group of tetrapods. Mol Biol Evol 30:1803–1807

    Article  PubMed  CAS  Google Scholar 

  • Magadán-Mompó S, Sánchez-Espinel C, Gambón-Deza F (2013) IgH loci of American alligator and saltwater crocodile shed light on IgA evolution. Immunogenetics:1–11

  • Marchalonis J (1969) Isolation and characterization of immunoglobulin-like proteins of the Australian lungfish (Neoceratodus forsteri). Aust J Exp Biol Med Sci 47:405–419

    Article  PubMed  CAS  Google Scholar 

  • Mashoof S, Goodroe A, Du C, Eubanks J, Jacobs N, Steiner J, Tizard I, Suchodolski J, Criscitiello M (2013) Ancient T-independence of mucosal IgX/A: gut microbiota unaffected by larval thymectomy in Xenopus laevis. Mucosal Immunol 6:358–368

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ohta Y, Flajnik M (2006) IgD, like IgM, is a primordial immunoglobulin class perpetuated in most jawed vertebrates. Proc Natl Acad Sci U S A 103:10723–10728

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Ota T, Rast JP, Litman GW, Amemiya CT (2003) Lineage-restricted retention of a primitive immunoglobulin heavy chain isotype within the Dipnoi reveals an evolutionary paradox. Proc Natl Acad Sci U S A 100:2501–2506

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Paul WE (2012) Fundamental Immunology seventh edition

  • Pfaffl MW (2001) A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res 29

  • Rumfelt LL, Diaz M, Lohr RL, Mochon E, Flajnik MF (2004) Unprecedented multiplicity of Ig transmembrane and secretory mRNA forms in the cartilaginous fish. J Immunol 173:1129–1139

    Article  PubMed  CAS  Google Scholar 

  • Santander J, Xin W, Yang Z, Curtiss R (2010) The aspartate-semialdehyde dehydrogenase of Edwardsiella ictaluri and its use as balanced-lethal system in fish vaccinology. PLoS One 5:e15944

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Sclavi B, Herrick J (2013) Slow Evolution of rag1 and pomc genes in vertebrates with large genomes. arXiv preprint arXiv:1302.2182

  • Tacchi L, Larragoite E, Salinas I (2013) Discovery of J chain in African lungfish (Protopterus dolloi, Sarcopterygii) using high throughput transcriptome sequencing: implications in mucosal immunity. PLoS One 8:e70650

    Article  PubMed Central  PubMed  CAS  Google Scholar 

  • Varriale S, Merlino A, Coscia MR, Mazzarella L, Oreste U (2010) An evolutionary conserved motif is responsible for Immunoglobulin heavy chain packing in the B cell membrane. Mol Phylogenet Evol 57:1238–1244

    Article  PubMed  CAS  Google Scholar 

  • Vervoort A (1980) Tetraploidy in Protopterus (Dipnoi). Experientia 36:294–296

    Article  Google Scholar 

  • Zhao Y, Pan-Hammarström Q, Yu S, Wertz N, Zhang X, Li N, Butler JE, Hammarström L (2006) Identification of IgF, a hinge-region-containing Ig class, and IgD in Xenopus tropicalis. Proc Natl Acad Sci U S A 103:12087–12092

    Article  PubMed Central  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This study was supported by NIH COBRE grant P20GM103452 (I.S), the National Basic Research Program of China (973 Program-2010CB945300), and the China National Natural Science Foundation (31100886).

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Authors and Affiliations

  1. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, National Engineering Laboratory for Animal Breeding, China Agricultural University, Beijing, 100193, People’s Republic of China

    Tianyi Zhang & Yaofeng Zhao

  2. Center for Evolutionary and Theoretical Immunology, University of New Mexico, Albuquerque, NM, 87131-0001, USA

    Luca Tacchi & Irene Salinas

  3. College of Animal Science and Technology, Henan University of Science and Technology, Henan, 471003, People’s Republic of China

    Zhiguo Wei

Authors
  1. Tianyi Zhang
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  2. Luca Tacchi
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  3. Zhiguo Wei
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  4. Yaofeng Zhao
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  5. Irene Salinas
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Corresponding authors

Correspondence to Yaofeng Zhao or Irene Salinas.

Additional information

Tianyi Zhang and Luca Tacchi contributed equally to this work.

Electronic supplementary material

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Supplemental Table 1

Primers used in this study (DOCX 32 kb)

Supplemental Table 2

Amino acid sequence identities of IgM isotypes in three lungfish (DOCX 20 kb)

Supplemental Table 3

Amino acid sequence identities of IgW and IgN in three lungfish (DOCX 20 kb)

Supplemental Table 4

VH gene usage in different IgH isotypes (DOCX 17 kb)

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Zhang, T., Tacchi, L., Wei, Z. et al. Intraclass diversification of immunoglobulin heavy chain genes in the African lungfish. Immunogenetics 66, 335–351 (2014). https://doi.org/10.1007/s00251-014-0769-2

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  • DOI: https://doi.org/10.1007/s00251-014-0769-2

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