, Volume 59, Issue 6, pp 493–506

Species-specific evolution of the FcR family in endothermic vertebrates

  • Svetlana A. Fayngerts
  • Alexander M. Najakshin
  • Alexander V. Taranin
Original Paper


In primates and rodents, the extended FcR family is comprised of three subsets: classical FcRs, structurally diverse cell surface receptors currently designated FCRL1–FCRL6, and intracellular proteins FCRLA and FCRLB. Using bioinformatic analysis, we revealed the FcR-like genes of the same three subsets in the genome of dog, another representative of placental mammals, and in the genome of short-tailed opossum, a representative of marsupials. In contrast, a single FcR-like gene was found in the current version of the chicken genome. This in silico finding was confirmed by the gene cloning and subsequent Southern blot hybridization. The chicken FCRL gene encodes a cell surface receptor with the extracellular region composed of four Ig-like domains of the D1-, D2-, D3-, and D4-subtypes. The gene is expressed in lymphoid and non-lymphoid tissues. Phylogenetic analysis of the mammalian and chicken genes suggested that classical FcRs, FCRLA, and FCRLB emerged after the mammalian–avian split but before the eutherian–marsupial radiation. The data obtained show that the repertoire of the classical FcRs and surface FcR-like proteins in mammalian species was shaped by an extensive recombination process, which resulted in domain shuffling and species-specific gain and loss of distinct exons or entire genes.


FcR family Domain shuffling Species-specific evolution 

Supplementary material


  1. Altschul SF, Madden TL, Schaffer AA, Zhang J, Zhang Z, Miller W, Lipman DJ (1997) Gapped BLAST and PSI-BLAST: a new generation of protein database search programs. Nucleic Acids Res 25:3389–3402PubMedCrossRefGoogle Scholar
  2. Burge C, Karlin S (1997) Prediction of complete gene structures in human genomic DNA. J Mol Biol 268:78–94PubMedCrossRefGoogle Scholar
  3. Chikaev NA, Bykova EA, Najakshin AM, Mechetina LV, Volkova OY, Peklo MM, Shevelev AY, Vlasik TN, Roesch A, Vogt T, Taranin AV (2005) Cloning and characterization of the human FCRL2 gene. Genomics 85:264–272PubMedCrossRefGoogle Scholar
  4. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162:156–159PubMedCrossRefGoogle Scholar
  5. Daeron M (1997) Fc receptor biology. Annu Rev Immunol 5:203–234CrossRefGoogle Scholar
  6. Davis RS, Wang YH, Kubagawa H, Cooper MD (2001) Identification of a family of Fc receptor homologs with preferential B cell expression. Proc Natl Acad Sci USA 98:9772–9777PubMedCrossRefGoogle Scholar
  7. Davis RS, Dennis G Jr, Odom MR, Gibson AW, Kimberly RP, Burrows PD, Cooper MD (2002a) Fc receptor homologs: newest members of a remarkably diverse Fc receptor gene family. Immunol Rev 190:123–136PubMedCrossRefGoogle Scholar
  8. Davis RS, Li H, Chen CC, Wang YH, Cooper MD, Burrows PD (2002b) Definition of an Fc receptor-related gene (FcRX) expressed in human and mouse B cells. Int Immunol 14:1075–1083PubMedCrossRefGoogle Scholar
  9. Davis RS, Stephan RP, Chen C-C, Dennis G Jr, Cooper MD (2004) Differential B cell expression of mouse Fc receptor homologs. Int Immunol 16:1343–1353PubMedCrossRefGoogle Scholar
  10. Davis RS, Ehrhardt GR, Leu CM, Hirano M, Cooper MD (2005) An extended family of Fc receptor relatives. Eur J Immunol 35:674–680PubMedCrossRefGoogle Scholar
  11. Ehrhardt GR, Davis RS, Hsu JT, Leu CM, Ehrhardt A, Cooper MD (2003) The inhibitory potential of Fc receptor homolog 4 on memory B cells. Proc Natl Acad Sci USA 100:13489–13494PubMedCrossRefGoogle Scholar
  12. Ehrhardt GR, Hsu JT, Gartland L, Leu CM, Zhang S, Davis RS, Cooper MD (2005) Expression of the immunoregulatory molecule FcRH4 defines a distinctive tissue-based population of memory B cells. J Exp Med 202:783–791PubMedCrossRefGoogle Scholar
  13. Ershova SA, Peklo MM, Shevelev AY, Najakshim AM, Mechetina LV, Volkova OY, Chikaev NA, Vlasik TN, Taranin AV (2004) IFGPG: a novel human member of the IFGP/IRTA/FcRH family that is selectively expressed by CD8 T and NK cells. Clin Invest Med Proceedings of the 12th International Congress of Immunology, July 18–23, 2004, Montreal, Canada 27(4):10CGoogle Scholar
  14. Ewald S, Freedman L, Sanders BG (1976) EA rosette-forming lymphoid cells in chickens: specificity of the Fc receptor and its relationship to other surface antigens. Immunology 31:847–854PubMedGoogle Scholar
  15. Facchetti F, Cella M, Festa S, Fremont DH, Colonna M (2002) An unusual Fc receptor-related protein expressed in human centroblasts. Proc Natl Acad Sci USA 99:3776–3781PubMedCrossRefGoogle Scholar
  16. Falini B, Tiacci E, Pucciarini A, Bigerna B, Kurth J, Hatzivassiliou G, Droetto S, Galletti BV, Gambacorta M, Orazi A, Pasqualucci L, Miller I, Kuppers R, Dalla-Favera R, Cattoretti G (2003) Expression of the IRTA1 receptor identifies intraepithelial and subepithelial marginal zone B cells of the mucosa-associated lymphoid tissue (MALT). Blood 102:3684–3692PubMedCrossRefGoogle Scholar
  17. Guselnikov SV, Ershova SA, Mechetina LV, Najakshin AM, Volkova OY, Alabyev BY, Taranin AV (2002) A family of highly diverse human and mouse genes structurally links leukocyte FcR, gp42 and PECAM-1. Immunogenetics 54:87–95PubMedCrossRefGoogle Scholar
  18. Guselnikov SV, Erilova AY, Najakshin AM, Cohen N, Rober J, Taranin AV (2004) FcR-like genes in the amphibian Xenopus: species-specific expansion, structure diversity, and developmental expression. Clin Invest Med. Proceedings of the 12th International Congress of Immunology, July 18–23, 2004, Montreal, Canada 27(4):82CGoogle Scholar
  19. Hatzivassiliou G, Miller I, Takizawa J, Palanisamy N, Rao PH, Iida S, Tagawa S, Taniwaki M, Russo J, Neri A, Cattoretti G, Clynes R, Mendelsohn C, Chaganti RS, Dalla-Favera R (2001) IRTA1 and IRTA2, novel immunoglobulin superfamily receptors expressed in B cells and involved in chromosome 1q21 abnormalities in B cell malignancy. Immunity 14:277–289PubMedCrossRefGoogle Scholar
  20. Hillier LW et al (2004) Sequence and comparative analysis of the chicken genome provide unique perspectives on vertebrate evolution. Nature 432:695–716CrossRefGoogle Scholar
  21. Hubbard T, Barker D, Birney E, Cameron G, Chen Y, Clark L, Cox T, Cuff J, Curwen V, Down T, Durbin R, Eyras E, Gilbert J, Hammond M, Huminiecki L, Kasprzyk A, Lehvaslaiho H, Lijnzaad P, Melsopp C, Mongin E, Pettett R, Pocock M, Potter S, Rust A, Schmidt E, Searle S, Slater G, Smith J, Spooner W, Stabenau A, Stalker J, Stupka E, Ureta-Vidal A, Vastrik I, Clamp M (2002) The Ensembl genome database project. Nucleic Acids Res 30:38–41PubMedCrossRefGoogle Scholar
  22. Hughes AL (1996) Gene duplication and recombination in the evolution of mammalian Fc receptors. J Mol Evol 43:4–10PubMedCrossRefGoogle Scholar
  23. Imboden JB, Eriksson EC, McCutcheon M, Reynolds CW, Seaman WE (1989) Identification and characterization of a cell-surface molecule that is selectively induced on rat lymphokine-activated killer cells. J Immunol 143:3100–3103PubMedGoogle Scholar
  24. Kumar S, Tamura K, Nei M (2004) MEGA3: Integrated software for molecular evolutionary genetics analysis and sequence alignment. Brief Bioinform 5:150–163PubMedCrossRefGoogle Scholar
  25. Leu CM, Davis RS, Gartland LA, Fine WD, Cooper MD (2005) FcRH1: an activation coreceptor on human B cells. Blood 105:1121–1126PubMedCrossRefGoogle Scholar
  26. Maltais LJ, Lovering RC, Taranin AV, Colonna M, Ravetch JV, Dalla-Favera R, Burrows PD, Cooper MD, Davis RS (2006) New nomenclature for Fc receptor-like molecules. Nat Immunol 7:431–432PubMedCrossRefGoogle Scholar
  27. Manghi MA, Venturiello SM, Gutierrez MI, Etchevierrigaray M, Margni RA (1987) Isolation and partial characterization of biologically active Fc receptor of chicken red cells. Biochim Biophys Acta 923:381–388PubMedGoogle Scholar
  28. Masuda K, Davis RS, Maruyama T, Zhang J, He T, Cooper MD, O-Wang J, Burrows PD (2005) FcRY, an Fc receptor related gene differentially expressed during B lymphocyte development and activation. Gene 363:32–40PubMedCrossRefGoogle Scholar
  29. Mechetina LV, Najakshin AM, Alabyev BY, Chikaev NA, Taranin AV (2002a) Identification of CD16-2, a novel mouse receptor homologous to CD16/Fc gamma RIII. Immunogenetics 54:463–468PubMedCrossRefGoogle Scholar
  30. Mechetina LV, Najakshin AM, Volkova OY, Guselnikov SV, Faizulin RZ, Alabyev BY, Chikaev NA, Vinogradova MS, Taranin AV (2002b) FCRL, a novel member of the leukocyte Fc receptor family possesses unique structural features. Eur J Immunol 32:87–96PubMedCrossRefGoogle Scholar
  31. Milanesi L, D’Angelo D, Rogozin IB (1999) GeneBuilder: interactive in silico prediction of gene structure. Bioinformatics 15:612–621PubMedCrossRefGoogle Scholar
  32. Miller I, Hatzivassiliou G, Cattoretti G, Mendelsohn C, Dalla-Favera R (2002) IRTAs: a new family of immunoglobulin-like receptors differentially expressed in B cells. Blood 99:2662–2669PubMedCrossRefGoogle Scholar
  33. Nakamura R, Sato Y, Takagi K, Sasaki N, Sawada J, Kitani S, Teshima R (2003) Presence and primary sequence of a high-affinity IgG receptor on canine mastocytoma (CM-MC) cells. Immunogenetics 55:271–274PubMedCrossRefGoogle Scholar
  34. Nakayama Y, Weissman SM, Bothwell AL (2001) BXMAS1 identifies a cluster of homologous genes differentially expressed in B cells. Biochem Biophys Res Commun 285:830–837PubMedCrossRefGoogle Scholar
  35. Nimmerjahn F, Bruhns P, Horiuchi K, Ravetch JV (2005) FcgammaRIV: a novel FcR with distinct IgG subclass specificity. Immunity 23:41–51PubMedCrossRefGoogle Scholar
  36. Pearson WR (1990) Rapid and sensitive sequence comparison with FASTP and FASTA. Methods Enzymol 183:63–98PubMedCrossRefGoogle Scholar
  37. Polson AG, Zheng B, Elkins K, Chang W, Du C, Dowd P, Yen L, Tan C, Hongo JA, Koeppen H, Ebens A (2006) Expression pattern of the human FcRH/IRTA receptors in normal tissue and in B-chronic lymphocytic leukemia. Int Immunol 18:1363–1373PubMedCrossRefGoogle Scholar
  38. Ravetch JV, Kinet J-P (1991) Fc receptors. Annu Rev Immunol 9:457–492PubMedGoogle Scholar
  39. Sambrook T, Fritsch EF, Maniatis T (eds) (1989) Molecular cloning: a laboratory manual, 2nd edn. Cold Spring Harbor Laboratory Press, Plainview, NYGoogle Scholar
  40. Smith J, Speed D, Law AS, Glass EJ, Burt DW (2004) In-silico identification of chicken immune-related genes. Immunogenetics 56:122–33PubMedCrossRefGoogle Scholar
  41. Thanaraj TA, Robinson AJ (2000) Prediction of exact boundaries of exons. Brief Bioinform 1:343–356PubMedCrossRefGoogle Scholar
  42. Thompson JD, Higgins DG, Gibson TJ (1994) CLUSTAL W: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, positions-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680PubMedCrossRefGoogle Scholar
  43. Tressler RL, Roth TF (1987) IgG receptors on the embryonic chick yolk sac. J Biol Chem 262:15406–15412PubMedGoogle Scholar
  44. Vernersson M, Aveskogh M, Munday B, Hellman L (2002) Evidence for an early appearance of modern post-switch immunoglobulin isotypes in mammalian evolution (II); cloning of IgE, IgG1 and IgG2 from a monotreme, the duck-billed platypus, Ornithorhynchus anatinus. Eur J Immunol 32:2145–2155PubMedCrossRefGoogle Scholar
  45. Warr GW, Magor KE, Higgins DA (1995) IgY: clues to the origins of modern antibodies. Immunol Today 16:392–398PubMedCrossRefGoogle Scholar
  46. West AP Jr, Herr AB, Bjorkman PJ (2004) The chicken yolk sac IgY receptor, a functional equivalent of the mammalian MHC-related Fc receptor, is a phospholipase A2 receptor homolog. Immunity 20:601–610PubMedCrossRefGoogle Scholar
  47. Wilson TJ, Colonna M (2005) A new Fc receptor homolog, FREB2, found in germinal center B cells. Genes Immun 6:341–346PubMedCrossRefGoogle Scholar
  48. Xu MJ, Zhao R, Zhao ZJ (2001) Molecular cloning and characterization of SPAP1, an inhibitory receptor. Biochem Biophys Res Commun 280:768–775PubMedCrossRefGoogle Scholar
  49. Xu MJ, Zhao R, Cao H, Zhao ZJ (2002) SPAP2, an Ig family receptor containing both ITIMs and ITAMs. Biochem Biophys Res Commun 293:1037–1046PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • Svetlana A. Fayngerts
    • 1
  • Alexander M. Najakshin
    • 1
  • Alexander V. Taranin
    • 1
  1. 1.Laboratory of ImmunogeneticsInstitute of Cytology and GeneticsNovosibirskRussia

Personalised recommendations