Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates

Abstract

The CD209 gene family that encodes C-type lectins in primates includes CD209 (DC-SIGN), CD209L (L-SIGN) and CD209L2. Understanding the evolution of these genes can help understand the duplication events generating this family, the process leading to the repeated neck region and identify protein domains under selective pressure. We compiled sequences from 14 primates representing 40 million years of evolution and from three non-primate mammal species. Phylogenetic analyses used Bayesian inference, and nucleotide substitutional patterns were assessed by codon-based maximum likelihood. Analyses suggest that CD209 genes emerged from a first duplication event in the common ancestor of anthropoids, yielding CD209L2 and an ancestral CD209 gene, which, in turn, duplicated in the common Old World primate ancestor, giving rise to CD209L and CD209. KA/KS values averaged over the entire tree were 0.43 (CD209), 0.52 (CD209L) and 0.35 (CD209L2), consistent with overall signatures of purifying selection. We also assessed the Toll-like receptor (TLR) gene family, which shares with CD209 genes a common profile of evolutionary constraint. The general feature of purifying selection of CD209 genes, despite an apparent redundancy (gene absence and gene loss), may reflect the need to faithfully recognize a multiplicity of pathogen motifs, commensals and a number of self-antigens.

This is a preview of subscription content

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

References

  1. Bashirova AA, Wu L, Cheng J, Martin TD, Martin MP, Benveniste RE et al. Novel member of the CD209 (DC-SIGN) gene family in primates. J Virol 2003; 77: 217–227.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  2. Koppel EA, van Gisbergen KP, Geijtenbeek TB, van Kooyk Y . Distinct functions of DC-SIGN and its homologues L-SIGN (DC-SIGNR) and mSIGNR1 in pathogen recognition and immune regulation. Cell Microbiol 2005; 7: 157–165.

    CAS  Article  PubMed  Google Scholar 

  3. Wu L, Kewalramani VN . Dendritic-cell interactions with HIV: infection and viral dissemination. Nat Rev Immunol 2006; 6: 859–868.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  4. Figdor CG, van KY, Adema GJ . C-type lectin receptors on dendritic cells and Langerhans cells. Nat Rev Immunol 2002; 2: 77–84.

    CAS  Article  PubMed  Google Scholar 

  5. Feinberg H, Guo Y, Mitchell DA, Drickamer K, Weis WI . Extended neck regions stabilize tetramers of the receptors DC-SIGN and DC-SIGNR. J Biol Chem 2005; 280: 1327–1335.

    CAS  Article  PubMed  Google Scholar 

  6. Yang Z . The power of phylogenetic comparison in revealing protein function. Proc Natl Acad Sci USA 2005; 102: 3179–3180.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  7. Nielsen R, Hellmann I, Hubisz M, Bustamante C, Clark AG . Recent and ongoing selection in the human genome. Nat Rev Genet 2007; 8: 857–868.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  8. Goodman M . The genomic record of Humankind's evolutionary roots. Am J Hum Genet 1999; 64: 31–39.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  9. Yang Z, Wong WS, Nielsen R . Bayes empirical bayes inference of amino acid sites under positive selection. Mol Biol Evol 2005; 22: 1107–1118.

    CAS  Article  PubMed  Google Scholar 

  10. Snyder GA, Colonna M, Sun PD . The structure of DC-SIGNR with a portion of its repeat domain lends insights to modeling of the receptor tetramer. J Mol Biol 2005; 347: 979–989.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  11. Barreiro LB, Patin E, Neyrolles O, Cann HM, Gicquel B, Quintana-Murci L . The heritage of pathogen pressures and ancient demography in the human innate-immunity CD209/CD209L region. Am J Hum Genet 2005; 77: 869–886.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  12. Wagner A . Rapid detection of positive selection in genes and genomes through variation clusters. Genetics 2007; 176: 2451–2463.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  13. Ortiz M, Bleiber G, Martinez R, Kaessmann H, Telenti A . Patterns of evolution of host proteins involved in retroviral pathogenesis. Retrovirology 2006; 3: 11.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sawyer SL, Emerman M, Malik HS . Ancient adaptive evolution of the primate antiviral DNA-editing enzyme APOBEC3G. PLoS Biol 2004; 2: E275.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Sawyer SL, Wu LI, Emerman M, Malik HS . Positive selection of primate TRIM5{alpha} identifies a critical species-specific retroviral restriction domain. Proc Natl Acad Sci USA 2005; 102: 2832–2837.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  16. Goldschmidt V, Ciuffi A, Ortiz M, Brawand D, Munoz M, Kaessmann H et al. Antiretroviral activity of ancestral TRIM5alpha. J Virol 2008; 82: 2089–2096.

    CAS  Article  PubMed  Google Scholar 

  17. Barreiro LB, Quintana-Murci L . DC-SIGNR neck-region polymorphisms and HIV-1 susceptibility: From population stratification to a possible advantage of the 7/5 heterozygous genotype. J Infect Dis 2006; 194: 1184–1185.

    CAS  Article  PubMed  Google Scholar 

  18. Wichukchinda N, Kitamura Y, Rojanawiwat A, Nakayama EE, Song H, Pathipvanich P et al. The polymorphisms in DC-SIGNR affect susceptibility to HIV type 1 infection. AIDS Res Hum Retroviruses 2007; 23: 686–692.

    CAS  Article  PubMed  Google Scholar 

  19. Martin MP, Lederman MM, Hutcheson HB, Goedert JJ, Nelson GW, van KY et al. Association of DC-SIGN promoter polymorphism with increased risk for parenteral, but not mucosal, acquisition of human immunodeficiency virus type 1 infection. J Virol 2004; 78: 14053–14056.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  20. Liu H, Hwangbo Y, Holte S, Lee J, Wang C, Kaupp N et al. Analysis of genetic polymorphisms in CCR5, CCR2, stromal cell-derived factor-1, RANTES, and dendritic cell-specific intercellular adhesion molecule-3-grabbing nonintegrin in seronegative individuals repeatedly exposed to HIV-1. J Infect Dis 2004; 190: 1055–1058.

    CAS  Article  PubMed  Google Scholar 

  21. Gramberg T, Zhu T, Chaipan C, Marzi A, Liu H, Wegele A et al. Impact of polymorphisms in the DC-SIGNR neck domain on the interaction with pathogens. Virology 2006; 347: 354–363.

    CAS  Article  PubMed  Google Scholar 

  22. Olesen R, Wejse C, Velez DR, Bisseye C, Sodemann M, Aaby P et al. DC-SIGN (CD209), pentraxin 3 and vitamin D receptor gene variants associate with pulmonary tuberculosis risk in West Africans. Genes Immun 2007; 8: 456–467.

    CAS  Article  PubMed  Google Scholar 

  23. Vannberg FO, Chapman SJ, Khor CC, Tosh K, Floyd S, Jackson-Sillah D et al. CD209 genetic polymorphism and tuberculosis disease. PLoS ONE 2008; 3: e1388.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Lynch M, Conery JS . The evolutionary fate and consequences of duplicate genes. Science 2000; 290: 1151–1155.

    CAS  Article  PubMed  Google Scholar 

  25. Medzhitov R . Toll-like receptors and innate immunity. Nat Rev Immunol 2001; 1: 135–145.

    CAS  Article  PubMed  Google Scholar 

  26. Edgar RC . MUSCLE: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 2004; 32: 1792–1797.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  27. Rice P, Longden I, Bleasby A . EMBOSS: the European Molecular Biology Open Software Suite. Trends Genet 2000; 16: 276–277.

    CAS  Article  PubMed  Google Scholar 

  28. Ronquist F, Huelsenbeck JP . MrBayes 3: Bayesian phylogenetic inference under mixed models. Bioinformatics 2003; 19: 1572–1574.

    CAS  Article  PubMed  Google Scholar 

  29. Yang Z . PAML: a program package for phylogenetic analysis by maximum likelihood. Comput Appl Biosci 1997; 13: 555–556.

    CAS  PubMed  Google Scholar 

  30. Yang Z, Bielawski JP . Statistical methods for detecting molecular adaptation. Trends Ecol Evol 2000; 15: 496–503.

    CAS  Article  PubMed  PubMed Central  Google Scholar 

  31. Yang Z, Nielsen R, Goldman N, Pedersen AM . Codon-substitution models for heterogeneous selection pressure at amino acid sites. Genetics 2000; 155: 431–449.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Yang Z . Likelihood ratio tests for detecting positive selection and application to primate lysozyme evolution. Mol Biol Evol 1998; 15: 568–573.

    CAS  Article  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Keith Mansfield and Kuei-Chin Lin from the New England Primate Center, and Charles Buillard and Eugène Chabloz from the Zoo of Servion for materials. This work was funded by the Swiss National Science Foundation and a grant for interdisciplinary research from the Faculty of Biology and Medicine of the University of Lausanne. This project has been funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract N01-CO-12400. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products or organizations imply endorsement by the US Government. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to A Telenti.

Additional information

Supplementary Information accompanies the paper on Genes and Immunity website (http://www.nature.com/gene)

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Ortiz, M., Kaessmann, H., Zhang, K. et al. The evolutionary history of the CD209 (DC-SIGN) family in humans and non-human primates. Genes Immun 9, 483–492 (2008). https://doi.org/10.1038/gene.2008.40

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/gene.2008.40

Keywords

  • C-type lectins
  • HIV
  • Ebola
  • Mycobacteria
  • innate immunity
  • DC-SIGN

Further reading

Search

Quick links