, Volume 57, Issue 1–2, pp 151–157 | Cite as

Origin and evolution of the Ig-like domains present in mammalian leukocyte receptors: insights from chicken, frog, and fish homologues

Brief Communication


In mammals many natural killer (NK) cell receptors, encoded by the leukocyte receptor complex (LRC), regulate the cytotoxic activity of NK cells and provide protection against virus-infected and tumor cells. To investigate the origin of the Ig-like domains encoded by the LRC genes, a subset of C2-type Ig-like domain sequences was compiled from mammals, birds, amphibians, and fish. Phylogenetic analysis of these sequences generated seven monophyletic groups in mammals (MI, MII, and FcI, FcIIa, FcIIb, FcIII, FcIV), two in chicken (CI, CII), four in frog (FI–FIV), and five in zebrafish (ZI–ZV). The analysis of the major groups supported the following order of divergence: ZI [or a common ancestor of ZI and F (a cluster composed of the FcIII and FIII groups)], F, CII (or a common ancestor of CII and MII), MII, and MI–CI. The relationships of the remaining groups were unclear, since the phylogenetic positions of these groups were not supported by high bootstrap values. Two main conclusions can be drawn from this analysis. First, the two groups of mammalian LRC sequences must diverged before the separation of the avian and mammalian lineages. Second, the mammalian LRC sequences are most closely related to the Fc receptor sequences and these two groups diverged before the separation of birds and mammals.


Leukocyte receptor complex Chicken Ig-like receptors Fc receptors Ig-like domain groups 



The Washington University Genome Sequencing Center, the DoE Joint Genome Institute and the Sanger Genomic Institute are acknowledged for making the chicken, frog and zebrafish sequences available. We thank the three anonymous reviewers for their comments and suggestions. We also thank Wojciech Makalowski and Dimitra Chalkia for valuable comments and discussions. This work was supported by a grant from the National Institutes of Health (GM20293) to M.N.

Supplementary material

251_2004_764_ESM_supp.pdf (189 kb)
(PDF 190 KB)


  1. Altschul SF, Gish W, Miller W, Myers EW, Lipman DJ (1990) Basic local alignment search tool. J Mol Biol 215:403–410CrossRefPubMedGoogle Scholar
  2. Bateman A, Coin L, Durbin R, Finn RD, Hollich V, Griffiths-Jones S, Khanna A, Marshall M, Moxon S, Sonnhammer EL, Studholme DJ, Yeats C, Eddy SR (2004) The Pfam protein families database. Nucleic Acids Res 32:138–141CrossRefGoogle Scholar
  3. Davis RS, Wang Y-H, Kubagawa H, Cooper MD (2001) Identification of a family of Fc receptor homologs with preferential B cell expression. Proc Natl Acad Sci USA 98:9772–9777CrossRefGoogle Scholar
  4. Dennis G Jr , Kubagawa H, Cooper MD (2000) Paired Ig-like receptor homologs in birds and mammals share a common ancestor with mammalian Fc receptors. Proc Natl Acad Sci USA 97:13245–13250CrossRefGoogle Scholar
  5. Hao L, Nei M (2004) Rapid expansion of killer cell immunoglobulin-like receptor genes in primates and their coevolution with MHC class I genes. Gene, in pressGoogle Scholar
  6. Hoelsbrekken SE, Nylenna O, Saether PC, Slettedal IO, Ryan JC, Fossum S, Dissen E (2003) Cutting edge: molecular cloning of a killer cell Ig-like receptor in the mouse and rat. J Immunol 170:2259–2263PubMedGoogle Scholar
  7. Hughes AL (2002) Evolution of the human killer cell inhibitory receptor family. Mol Phylogenet Evol 25:330–340CrossRefPubMedGoogle Scholar
  8. Hughes AL, Nei M (1988) Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 355:167–170CrossRefGoogle Scholar
  9. Klein J, Hořejší V (1997) Immunology, 2nd edn. Oxford Blackwell Science, OxfordGoogle Scholar
  10. Kumar S, Tamura K, Jakobsen IB, Nei M (2001) MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 17:1244–1245CrossRefPubMedGoogle Scholar
  11. Lanier LM (2003) Natural killer cell receptor signaling. Curr Opin Immunol 15:308–314Google Scholar
  12. Letunic I, Copley RR, Schmidt S, Ciccarelli FD, Doerks T, Schultz J, Ponting CP, Bork P (2004) SMART 4.0: towards genomic data integration. Nucleic Acids Res 32:142–144CrossRefGoogle Scholar
  13. Martin AM, Kulski JK, Witt C, Pontarotti P, Christiansen FT (2002) Leukocyte Ig-like receptor complex (LRC) in mice and men. Trends Immunol 23:81–88CrossRefGoogle Scholar
  14. Maruoka T, Nagata T, Kasahara M (2004) Identification of the rat IgA Fc receptor encoded in the leukocyte receptor complex. Immunogenetics 55:712–716CrossRefGoogle Scholar
  15. 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 99:2662–2669CrossRefGoogle Scholar
  16. Morton HC, Pleass RJ, Storset AK, Dissen E, Williams JL, Brandtzaeg P, Woof JM (2004) Cloning and characterization of an immunoglobulin A Fc receptor from cattle. Immunology 111:201–211CrossRefGoogle Scholar
  17. Nei M, Kumar S (2000) Molecular evolution and phylogenetics. Oxford University Press, New YorkGoogle Scholar
  18. Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882CrossRefPubMedGoogle Scholar
  19. Trowsdale J, Barten R, Haude A, Stewart CA, Beck S, Wilson MJ (2001) The genomic context of natural killer receptor extended gene families. Immunol Rev 181:20–38CrossRefPubMedGoogle Scholar
  20. Volz A, Wende H, Laun K, Ziegler A (2001) Genesis of the ILT/LIR/MIR clusters within the human leukocyte receptor complex. Immunol Rev 181:39–51CrossRefGoogle Scholar
  21. Yeh R-F, Lim LP, Burge CB (2001) Computational inference of homologous gene structures in the human genome. Genome Res 11:803–816CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2005

Authors and Affiliations

  1. 1.Department of Biology, Institute of Molecular Evolutionary GeneticsPennsylvania State UniversityUniversity ParkUSA

Personalised recommendations