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Positive selection of HIV host factors and the evolution of lentivirus genes.

ABSTRACT: BACKGROUND: Positive selection of host proteins that interact with pathogens can indicate factors relevant for infection and potentially be a measure of pathogen driven evolution. RESULTS: Our analysis of 1439 primate genes and 175 lentivirus genomes points to specific host factors of high genetic variability that could account for differences in susceptibility to disease and indicate specific mechanisms of host defense and pathogen adaptation. We find that the largest amount of genetic change occurs in genes coding for cellular membrane proteins of the host as well as in the viral envelope genes suggesting cell entry and immune evasion as the primary evolutionary interface between host and pathogen. We additionally detect the innate immune response as a gene functional group harboring large differences among primates that could potentially account for the different levels of immune activation in the HIV/SIV primate infection. We find a significant correlation between the evolutionary rates of interacting host and viral proteins pointing to processes of the host-pathogen biology that are relatively conserved among species and to those undergoing accelerated genetic evolution. CONCLUSIONS: These results indicate specific host factors and their functional groups experiencing pathogen driven evolutionary selection pressures. Individual host factors pointed to by our analysis might merit further study as potential targets of antiretroviral therapies.

SUBMITTER: Bozek K

PROVIDER: S-EPMC2906474 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Positive selection of HIV host factors and the evolution of lentivirus genes.

Bozek Katarzyna K Lengauer Thomas T

BMC evolutionary biology 20100618

<h4>Background</h4>Positive selection of host proteins that interact with pathogens can indicate factors relevant for infection and potentially be a measure of pathogen driven evolution.<h4>Results</h4>Our analysis of 1439 primate genes and 175 lentivirus genomes points to specific host factors of high genetic variability that could account for differences in susceptibility to disease and indicate specific mechanisms of host defense and pathogen adaptation. We find that the largest amount of gen ...[more]

PMID: 20565842

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Project description:Gene regulatory factors (GRFs), such as transcription factors, co-factors and histone-modifying enzymes, play many important roles in modifying gene expression in biological processes. They have also been proposed to underlie speciation and adaptation. To investigate potential contributions of GRFs to primate evolution, we analyzed GRF genes in 27 publicly available primate genomes. Genes coding for zinc finger (ZNF) proteins, especially ZNFs with a Krüppel-associated box (KRAB) domain were the most abundant TFs in all genomes. Gene numbers per TF family differed between all species. To detect signs of positive selection in GRF genes we investigated more than 3,000 human GRFs with their more than 70,000 orthologs in 26 non-human primates. We implemented two independent tests for positive selection, the branch-site-model of the PAML suite and aBSREL of the HyPhy suite, focusing on the human and great ape branch. Our workflow included rigorous procedures to reduce the number of false positives: excluding distantly similar orthologs, manual corrections of alignments, and considering only genes and sites detected by both tests for positive selection. Furthermore, we verified the candidate sites for selection by investigating their variation within human and non-human great ape population data. In order to approximately assign a date to positively selected sites in the human lineage, we analyzed archaic human genomes. Our work revealed with high confidence five GRFs that have been positively selected on the human lineage and one GRF that has been positively selected on the great ape lineage. These GRFs are scattered on different chromosomes and have been previously linked to diverse functions. For some of them a role in speciation and/or adaptation can be proposed based on the expression pattern or association with human diseases, but it seems that they all contributed independently to human evolution. Four of the positively selected GRFs are KRAB-ZNF proteins, that induce changes in target genes co-expression and/or through arms race with transposable elements. Since each positively selected GRF contains several sites with evidence for positive selection, we suggest that these GRFs participated pleiotropically to phenotypic adaptations in humans.

Project description:Hosts and viruses are locked in an evolutionary arms race. Hosts are constantly evolving to suppress virulence and replication, while viruses, which are reliant on host machinery for survival and reproduction, develop counterstrategies to escape this immune defense. Viruses must also adapt to novel conditions while establishing themselves in a host species. Both processes provide strong selection for viral adaptation. Understanding adaptive evolution in insect viruses can help us to better understand adaptive evolution in general and is important due to the use of these viruses as biocontrol agents and for protecting ecologically or economically important species from outbreaks. Here we examine the molecular evolution of baculoviruses and nudiviruses, a group of insect-infecting viruses with key roles in biocontrol. We looked for signatures of selection between genomes of baculoviruses infecting a range of species and within a population of baculoviruses. Both analyses found only a few strong signatures of positive selection, primarily in replication- and transcription-associated genes and several structural protein genes. In both analyses, we detected a conserved complex of genes, including the helicase gene, showing consistently high levels of adaptive evolution, suggesting that they may be key in antagonistic coevolution to escape host suppression. These genes are integral to the baculovirus life cycle and may be good focal genes for developing baculoviruses as effective biocontrol agents or for targeting baculoviruses infecting ecologically relevant species. Recombination and complex genomes make evolution in these double-stranded DNA viruses more efficient than that in smaller RNA viruses with error-prone replication, as seen via signatures of selection in specific genes within a population of baculoviruses.IMPORTANCE Most viral evolutionary studies focus on RNA viruses. While these viruses cause many human and animal diseases, such studies leave us with a lesser understanding of how DNA viruses adapt to hosts and how the host responds to these pathogens. In this paper, we focus on the evolution of baculoviruses, a group of insect-infecting DNA viruses, many of which have been used in biocontrol. We find that most of the genome is under purifying selection, with only a few key genes evolving adaptively. Our results provide a glimpse into how DNA viruses differ from RNA viruses in their evolutionary dynamics and identify genes that are key to DNA virus adaptation, improving our understanding of how this group of pathogens evolves.

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Positive selection of HIV host factors and the evolution of lentivirus genes.

Publications

Positive selection of HIV host factors and the evolution of lentivirus genes.

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