Details:

Alternative Title:
PLoS One
Personal Author:
Chen, Ping; Gan, Yun; Han, Na; Fang, Wei; Li, Jiafu; ... More +
Chen, Ping; Gan, Yun; Han, Na; Fang, Wei; Li, Jiafu; Zhao, Fei; Hu, Kanghong; Rayner, Simon; Less -
Description:
Introduction The Hepatitis B Virus (HBV) genome contains four ORFs, S (surface), P (polymerase), C (core) and X. S is completely overlapped by P and as a consequence the overlapping region is subject to distinctive evolutionary constraints compared to the remainder of the genome. Specifically, a non-synonymous substitution in one coding frame may produce a synonymous substitution in the alternative frame, suggesting a possible conflict between requirements for diversifying and purifying forces. To examine how these contrasting requirements are balanced within this region, we investigated the relationship amongst positive selection sites, conserved regions, epitopes and elements of protein structure to consider how HBV balances the contrasting evolutionary pressures. Methodology/Results 323 HBV genotype D genome sequences were collected and analyzed to identify sites under positive selection and highly conserved regions. Epitopes sequences were retrieved from previously published experimental studies stored in the Immune Epitope Database. Predicted secondary structures were used to investigate the association between structure and conservation. Entropy was used as a measure of conservation and bivariate logistic regression was used to investigate the relationship between positive selection/conserved sites and epitope/secondary structure regions. Our results indicate: (i) conservation in S is primarily dictated by α-helix elements in the protein structure, (ii) variable residues are mainly located in PreS, the major hydrophilic region (MHR) and the C-terminus, (iii) epitopes in S, which are directly targeted by the host immune system, are significantly associated with sites under positive selection. Conclusions The highly variable spacer domain in P, which corresponds to PreS in S, appears to act as a harbor for the accumulation of mutations that can provide flexibility for conformational changes and responding to immune pressure.
Subject:
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Biology
Computational Biology
Conserved Sequence
Databases, Genetic
DNA-Directed DNA Polymerase
Epitopes
Evolution, Molecular
Genome, Viral
Hepatitis B Virus
Humans
Medicine
Microbial Viability
Models, Molecular
Open Reading Frames
Protein Structure, Secondary
Protein Structure, Tertiary
Research Article
RNA-Directed DNA Polymerase
Selection, Genetic
Viral Proteins

Source:
PLoS One. 2013; 8(4).;
Document Type:
Journal Article;
Collection(s):
CDC Public Access
Main Document Checksum:
[+]
urn:sha256:e1d0061106374188626c1e2e20c8b264bc07602096540cb1949b3adefc6b5f6e
File Type:

Supporting Files

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