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RESEARCH PRODUCT
Comparative analysis of variation and selection in the HCV genome
Fernando González-candelasJuan ÁNgel Patiño-galindosubject
CD4-Positive T-Lymphocytes0301 basic medicineMicrobiology (medical)GenotypeEpitopes T-LymphocyteGenome ViralHepacivirusCD8-Positive T-LymphocytesBiologyGenoma humàMicrobiologyGenomeEpitopeNucleic acid secondary structureEvolution MolecularViral Proteins03 medical and health sciencesNegative selection0302 clinical medicineGenotypeGeneticsHumansCoding regionAmino Acid SequenceGenetic variabilitySelection GeneticMolecular BiologyGenePhylogenyEcology Evolution Behavior and SystematicsSelection (genetic algorithm)GeneticsGenetic VariationSequence Analysis DNAHepatitis C AntibodiesHepatitis C ChronicVirus030104 developmental biologyInfectious DiseasesRNA Viral030211 gastroenterology & hepatologydescription
AbstractGenotype 1 of the hepatitis C virus (HCV) is the most prevalent of the variants of this virus. Its two main subtypes, HCV-1a and HCV-1b, are associated to differences in epidemic features and risk groups, despite sharing similar features in most biological properties. We have analyzed the impact of positive selection on the evolution of these variants using complete genome coding regions, and compared the levels of genetic variability and the distribution of positively selected sites. We have also compared the distributions of positively selected and conserved sites considering different factors such as RNA secondary structure, the presence of different epitopes (antibody, CD4 and CD8), and secondary protein structure. Less than 10% of the genome was found to be under positive selection, and purifying selection was the main evolutionary force in both subtypes. We found differences in the number of positively selected sites between subtypes in several genes (Core, HVR2 inE2, P7, helicase inNS3andNS4a).Heterozygosity values in positively selected sites and the rate of non-synonymous substitutions were significantly higher in subtype HCV-1b. Logistic regression analyses revealed that similar selective forces act at the genome level in both subtypes: RNA secondary structure and CD4 T-cell epitopes are associated with conservation, while CD8 T-cell epitopes are associated with positive selection in both subtypes. These results indicate that similar selective constraints are acting along HCV-1a and HCV-1b genomes, despite some differences in the distribution of positively selected sites at independent genes.
year | journal | country | edition | language |
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2016-09-30 |