4.5 Article

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

Journal

GENES AND IMMUNITY
Volume 9, Issue 6, Pages 483-492

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/gene.2008.40

Keywords

C-type lectins; HIV; Ebola; mycobacteria; innate immunity; DC-SIGN

Funding

  1. Swiss National Science Foundation
  2. Faculty of Biology and Medicine of the University of Lausanne
  3. National Cancer Institute
  4. National Institutes of Health [N01-CO-12400]
  5. Intramural Research Program of the NIH
  6. Center for Cancer Research

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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. K(A)/K(S) 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.

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