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Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R

Genes & Immunity volume 2, pages 335–342 (2001)Cite this article

Abstract

N-formylpeptides are phagocyte chemoattractants that act by binding to two structurally related receptors, FPR (formylpeptide receptor) and FPRL1R (FPR-like-1 receptor), which are encoded by the human genes FPR1 and FPRL1. Single nucleotide polymorphisms (SNPs) in the FPR coding region have been reported and two have been associated with the disease juvenile periodontitis; however, their frequency and linkage relationships are unknown. Here we systematically analyzed polymorphism in the open reading frames of FPR1 and FPRL1 by direct sequencing of cloned alleles from random blood donors from North America. For FPR1 we detected five non-synonymous SNPs and two synonymous SNPs in a sample of 26 chromosomes one each from 17 Caucasian and nine black random blood donors. Although all five non-synonymous SNPs were common in Caucasians, Blacks, and Asians, notable differences in allele frequency were found for each SNP in the different racial groups, suggesting differential selective pressures. We found that the FPR1 polymorphisms are linked in 15 common haplotypes. No polymorphisms were detected in FPRL1 after sampling 44 chromosomes from 36 random blood donors from the same three racial groups. Thus FPR1 and FPRL1, though they originated from a common gene, appear to have undergone markedly different evolutionary events.

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References

  1. Rosenberg HF, Gallin JI Inflammation. In: Paul WE (ed). Fundamental Immunology Lippincott-Raven Publishers:Philadelphia 1999 pp 1051–1066

  2. Zimmerman PA, Buckler-White A, Alkhatib G et al Inherited resistance to HIV-1 conferred by an inactivating mutation in CC chemokine receptor 5: studies in populations with contrasting clinical phenotypes, defined racial background, and quantified risk Mol Med 1997 3 23–36

    Article  CAS  Google Scholar 

  3. Childs B, Moxon ER, Winkelstein JA Genetics and infectious diseases. In: King RA, Rotter JI, Motulsky AG (ed) The Genetic Basis of Common Diseases Oxford University Press: New York 1992 71–91

    Google Scholar 

  4. Gwinn MR, Sharma A, De Nardin E Single nucleotide polymorphisms of the N-formyl peptide receptor in localized juvenile periodontitis J Periodontol 1999 70 1194–201

    Article  CAS  Google Scholar 

  5. Perez HD, Kelly E, Elfman F, Armitage G, Winkler J Defective polymorphonuclear leukocyte formyl peptide receptor(s) in juvenile periodontitis J Clin Invest 1991 87 971–976

    Article  CAS  Google Scholar 

  6. Gao JL, Lee EJ, Murphy PM Impaired antibacterial host defense in mice lacking the N-formylpeptide receptor J Exp Med 1999 189 657–662

    Article  CAS  Google Scholar 

  7. Perez HD, Holmes R, Kelly E, McClary J, Chou Q, Andrews WH Cloning of the gene coding for a human receptor for formyl peptides. Characterization of a promoter region and evidence for polymorphic expression Biochemistry 1992 31 11595–11599

    Article  CAS  Google Scholar 

  8. Murphy PM, Tiffany HL, McDermott D, Ahuja SK Sequence and organization of the human N-formyl peptide receptor-encoding gene Gene 1993 133 285–290

    Article  CAS  Google Scholar 

  9. Bao L, Gerard NP, Eddy RL Jr, Shows TB, Gerard C Mapping of genes for the human C5a receptor (C5AR), human FMLP receptor (FPR), and two FMLP receptor homologue orphan receptors (FPRH1, FPRH2) to chromosome 19 Genomics 1992 13 437–440

    Article  CAS  Google Scholar 

  10. Boulay F, Tardif M, Brouchon L, Vignais P The human N-formylpeptide receptor. Characterization of two cDNA isolates and evidence for a new subfamily of G-protein-coupled receptors Biochemistry 1990 29 11123–11133

    Article  CAS  Google Scholar 

  11. Gao JL, Becker EL, Freer RJ, Muthukumaraswamy N, Murphy PM A high potency nonformylated peptide agonist for the phagocyte N-formylpeptide chemotactic receptor J Exp Med 1994 180 2191–2197

    Article  CAS  Google Scholar 

  12. Murphy PM, Ozcelik T, Kenney RT, Tiffany HL, McDermott D, Francke U A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family J Biol Chem 1992 267 7637–7643

    CAS  PubMed  Google Scholar 

  13. Durstin M, Gao JL, Tiffany HL, McDermott D, Murphy PM Differential expression of members of the N-formylpeptide receptor gene cluster in human phagocytes Biochem Biophys Res Commun 1994 201 174–179

    Article  CAS  Google Scholar 

  14. Yeagle PL, Danis C, Choi G, Alderfer JL, Albert AD Three dimensional structure of the seventh transmembrane helical domain of the G-protein receptor, rhodopsin Mol Vis 2000 6 125–131

    CAS  PubMed  Google Scholar 

  15. Palczewski K, Kumasaka T, Hori T et al Crystal structure of rhodopsin: a G protein-coupled receptor Science 2000 289 739–745

    Article  CAS  Google Scholar 

  16. Perez HD, Holmes R, Kelly E, McClary J, Andrews WH Cloning of a cDNA encoding a receptor related to the formyl peptide receptor of human neutrophils Gene 1992 118 303–304

    Article  CAS  Google Scholar 

  17. Ye RD, Quehenberger O, Thomas KM et al The rabbit neutrophil N-formyl peptide receptor. c-DNA cloning, expression, and structure/function implications J Immunol 1993 150 1383–1394

    CAS  PubMed  Google Scholar 

  18. Alvarez V, Coto E, Setien F, Gonzalez-Roces S, Lopez-Larrea C Molecular evolution of the N-formyl peptide and C5a receptors in non- human primates Immunogenetics 1996 44 446–452

    Article  CAS  Google Scholar 

  19. Gao JL, Chen H, Filie JD, Kozak CA, Murphy PM Differential expansion of the N-formylpeptide receptor gene cluster in human and mouse Genomics 1998 51 270–276

    Article  CAS  Google Scholar 

  20. Kumar S, Tamura K, Nei M Mega: molecular evolutionary genetics analysis software for microcomputers Comput Appl Biosci 1994 10 189–191

    CAS  PubMed  Google Scholar 

  21. Cargill M, Altshuler D, Ireland J et al Characterization of single-nucleotide polymorphisms in coding regions of human genes Nat Genet 1999 22 231–238

    Article  CAS  Google Scholar 

  22. Nei M, Li WH Mathematical model for studying genetic variation in terms of restriction endonucleases Proc Natl Acad Sci USA 1979 76 5269–5273

    Article  CAS  Google Scholar 

  23. Halushka MK, Fan JB, Bentley K et al Patterns of single-nucleotide polymorphisms in candidate genes for blood-pressure homeostasis Nat Genet 1999 22 239–247

    Article  CAS  Google Scholar 

  24. Murphy PM The N-formylpeptide chemotactic receptor. In: Horuk R (ed) Chemoattractant Ligands and their Receptors CRC Press: Boca Raton 1996 269–299

    Google Scholar 

  25. Murphy PM Molecular mimicry and the generation of host defense protein diversity [letter] Cell 1993 72 823–826

    Article  CAS  Google Scholar 

  26. Zhang J, Rosenberg HF Sequence variation at two eosinophil-associated ribonuclease loci in humans Genetics 2000 156 1949–1958

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Karlen A Man and Microbes: Disease and Plagues in History and Modern Times Putnam: New York 1995 pp 1–266

  28. Mills JS, Miettinen HM, Cummings D, Jesaitis AJ Characterization of the binding site on the formyl peptide receptor using three receptor mutants and analogs of Met-Leu-Phe and Met-Met-Trp- Leu-Leu J Biol Chem 2000 275 39012–39017

    Article  CAS  Google Scholar 

  29. Prossnitz ER, Kim CM, Benovic JL, Ye RD Phosphorylation of the N-formyl peptide receptor carboxyl terminus by the G protein-coupled receptor kinase, grk2 J Biol Chem 1995 270 1130–1137

    Article  CAS  Google Scholar 

  30. Miettinen HM, Mills JS, Gripentrog JM, Dratz EA, Granger BL, Jesaitis AJ The ligand binding site of the formyl peptide receptor maps in the transmembrane region J Immunol 1997 159 4045–4054

    CAS  PubMed  Google Scholar 

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Acknowledgements

We thank Dr George Zhang of the Laboratory of Host Defenses of the National Institute of Allergy and Infectious Disease of the National Institutes of Health, Bethesda, MD for helpful discussions regarding FPR evolution.

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Authors and Affiliations

  1. Molecular Signaling Section, Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA

    A Sahagun-Ruiz, JS Colla, J Juhn, J-L Gao, PM Murphy & DH McDermott

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  1. A Sahagun-Ruiz
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  2. JS Colla
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  3. J Juhn
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  4. J-L Gao
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  5. PM Murphy
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Corresponding author

Correspondence to DH McDermott.

Additional information

ASR is supported by a grant from the Pan-American Fellowship, US-Mexico Cooperative Biomedical and Behavioral Research Program (CoBRP), United States National Institutes of Health and Mexican National Council for Science and Technology (CONACYT).

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Sahagun-Ruiz, A., Colla, J., Juhn, J. et al. Contrasting evolution of the human leukocyte N-formylpeptide receptor subtypes FPR and FPRL1R . Genes Immun 2, 335–342 (2001). https://doi.org/10.1038/sj.gene.6363787

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