Evolutionary trajectories of primate genes involved in HIV pathogenesis.

Details

Serval ID
serval:BIB_9538BDFBC951
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Evolutionary trajectories of primate genes involved in HIV pathogenesis.
Journal
Molecular Biology and Evolution
Author(s)
Ortiz Millan, Ciuffi Angela, Xenarios Ioannis, Martin Olivier, Patin Etienne, Guex Nicolas, Quintana-Murci Luis, Telenti Amalio
ISSN
1537-1719[electronic]
Publication state
Published
Issued date
2009
Volume
26
Number
12
Pages
2865-2875
Language
english
Abstract
The current availability of five complete genomes of different primate species allows the analysis of genetic divergence over the last 40 million years of evolution. We hypothesized that the interspecies differences observed in susceptibility to HIV-1 would be influenced by the long-range selective pressures on host genes associated with HIV-1 pathogenesis. We established a list of human genes (n = 140) proposed to be involved in HIV-1 biology and pathogenesis and a control set of 100 random genes. We retrieved the orthologous genes from the genome of humans and of four nonhuman primates (Pan troglodytes, Pongo pygmaeus abeli, Macaca mulatta, and Callithrix jacchus) and analyzed the nucleotide substitution patterns of this data set using codon-based maximum likelihood procedures. In addition, we evaluated whether the candidate genes have been targets of recent positive selection in humans by analyzing HapMap Phase 2 single-nucleotide polymorphisms genotyped in a region centered on each candidate gene. A total of 1,064 sequences were used for the analyses. Similar median K(A)/K(S) values were estimated for the set of genes involved in HIV-1 pathogenesis and for control genes, 0.19 and 0.15, respectively. However, genes of the innate immunity had median values of 0.37 (P value = 0.0001, compared with control genes), and genes of intrinsic cellular defense had K(A)/K(S) values around or greater than 1.0 (P value = 0.0002). Detailed assessment allowed the identification of residues under positive selection in 13 proteins: AKT1, APOBEC3G, APOBEC3H, CD4, DEFB1, GML, IL4, IL8RA, L-SIGN/CLEC4M, PTPRC/CD45, Tetherin/BST2, TLR7, and TRIM5alpha. A number of those residues are relevant for HIV-1 biology. The set of 140 genes involved in HIV-1 pathogenesis did not show a significant enrichment in signals of recent positive selection in humans (intraspecies selection). However, we identified within or near these genes 24 polymorphisms showing strong signatures of recent positive selection. Interestingly, the DEFB1 gene presented signatures of both interspecies positive selection in primates and intraspecies recent positive selection in humans. The systematic assessment of long-acting selective pressures on primate genomes is a useful tool to extend our understanding of genetic variation influencing contemporary susceptibility to HIV-1.
Keywords
APOBEC3, Evolutionary Genomics, HapMap, TRIM5, Tetherin, Amino-Acid Sites, Positive Selection, Natural-Selection, Retroviral Restriction, Human Genome, Adaptive Evolution, Sequence Alignment, Proteins, Trim5-Alpha, Infection
Pubmed
Web of science
Open Access
Yes
Create date
03/12/2009 10:58
Last modification date
20/08/2019 15:57
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