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. 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.

The DC-SIGN of Zebrafish: Insights into the Existence of a CD209 Homologue in a Lower Vertebrate and Its Involvement in Adaptive Immunity

“…Structurally, the fish CD209 lacks tandem repeats in the neck region, which is the same situation seen in primate CD209L2 molecules (although the partial CD209L2 has a shorter or interceptive region). This, at least in part, supports the idea that the ancestor of the modern CD209 family was most likely a member that resembled CD209L2 (42).…”

“…The inserted ancestral motif increased to seven or eight repeats after duplications to form a complete neck region. This finally gave rise to CD209L and CD209, where the extant CD209L2, which lacks tandem repeats in the neck region, kept its characterization from the first duplication and became a pseudogene in partial primates (42).…”

Polymorphisms in DC-SIGN and L-SIGN genes are associated with HIV-1 vertical transmission in a Northeastern Brazilian population

“…In contrast, in Indian population this region was not implicated in viral transmission [27]. The great conservation of DC-SIGN exon 4 tandem repeats polymorphisms in different populations, suggests a fundamental role for this region, not affected by selective pressure [23,29,30].…”

Evolution and diversity of copy number variation in the great ape lineage

“…By this definition, we identified 86 putative gene losses along the branches leading to the human lineage-40 since divergence from chimpanzee. A search of these ORFs against the RefSeq protein database yielded not only previously annotated gene-loss events, such as the human-specific SIGLEC13 (Wang et al 2012) and CLECM4 (Ortiz et al 2008) deletions, but 42 pre-viously unannotated or only predicted protein-coding genes with homology with other genes, 28 of which intersect highly conserved elements (HCEs) (Siepel et al 2005). In total we identified 180 kb of highly conserved sequence within these fixed deletions, a marked depletion compared to the 3%-8% of the human reference genome encompassed by HCEs.…”