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Detection of site-specific positive Darwinian selection on pandemic influenza A/H1N1 virus genome: integrative approaches

Identifieur interne : 001705 ( Istex/Corpus ); précédent : 001704; suivant : 001706

Detection of site-specific positive Darwinian selection on pandemic influenza A/H1N1 virus genome: integrative approaches

Auteurs : Ramaiah Arunachalam

Source :

RBID : ISTEX:90E94B1E6C56E7D6EB85AE7F147A15EFF402162E

English descriptors

Abstract

Abstract: In the twenty-first century, the first pandemic novel human influenza A/H1N1virus (NIV) outbreak was reported at Mexico and USA on March and early April, 2009 respectively. The outbreak occurred among human populations due to the presence of meager or no immune response against newly emerged viruses. The success of vaccines and drugs depends on their low susceptibility to the formation of escape mutants in virus. Identification of excess, non-synonymous substitutions over synonymous ones is a main indicator of positive Darwinian selection in protein-coding genes of NIVs. The positive Darwinian selection operating on each site of proteins were inferred by computing ω, the ratio of the non-synonymous/synonymous substitutions [dN/dS (or) Ka/Ks], which was calculated by three different methods in terms of codon-based maximum likelihood, branch-site and empirical Bayesian methods under various models. Totally, nine sites from PB2, PB1, HA, M2 and NS1 are inferred as positively selected. The function for amino acid sites of NIVs proteins under positive selection are inferred by comparing the sites with experimentally determined functionally known amino acid sites. Completely 4 positively selected sites of PB1, HA and M2 are found to be involved in B-cell epitopes (BCEs). Interestingly, most of these sites are also involving in T-cell epitopes (TCEs). However, more sites under positive selection forces are involved in TCEs than those of BCEs. Amino acid sites engaged in both BCEs and TCEs should be measured as highly suitable targets, because these sites could induce the strong humoral and cellular immune responses against targets.

Url:
DOI: 10.1007/s10709-013-9713-x

Links to Exploration step

ISTEX:90E94B1E6C56E7D6EB85AE7F147A15EFF402162E

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], which was calculated by three different methods in terms of codon-based maximum likelihood, branch-site and empirical Bayesian methods under various models. Totally, nine sites from PB2, PB1, HA, M2 and NS1 are inferred as positively selected. The function for amino acid sites of NIVs proteins under positive selection are inferred by comparing the sites with experimentally determined functionally known amino acid sites. Completely 4 positively selected sites of PB1, HA and M2 are found to be involved in B-cell epitopes (BCEs). Interestingly, most of these sites are also involving in T-cell epitopes (TCEs). However, more sites under positive selection forces are involved in TCEs than those of BCEs. Amino acid sites engaged in both BCEs and TCEs should be measured as highly suitable targets, because these sites could induce the strong humoral and cellular immune responses against targets.</Para>
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<Heading>Keywords</Heading>
<Keyword>Novel influenza A/H1N1 virus</Keyword>
<Keyword>Genome</Keyword>
<Keyword>Natural selection</Keyword>
<Keyword>Amino acid function</Keyword>
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<title>Detection of site-specific positive Darwinian selection on pandemic influenza A/H1N1 virus genome: integrative approaches</title>
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<title>Detection of site-specific positive Darwinian selection on pandemic influenza A/H1N1 virus genome: integrative approaches</title>
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<namePart type="given">Ramaiah</namePart>
<namePart type="family">Arunachalam</namePart>
<affiliation>Sri Paramakalyani Centre for Environmental Sciences, Manonmaniam Sundaranar University, 627412, Alwarkurichi, Tamil Nadu, India</affiliation>
<affiliation>Structural Bioinformatics Laboratory, Department of Biosciences, Åbo Akademi University, 20520, Turku, Finland</affiliation>
<affiliation>E-mail: arunachalamphd@gmail.com</affiliation>
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<dateCreated encoding="w3cdtf">2012-11-15</dateCreated>
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<abstract lang="en">Abstract: In the twenty-first century, the first pandemic novel human influenza A/H1N1virus (NIV) outbreak was reported at Mexico and USA on March and early April, 2009 respectively. The outbreak occurred among human populations due to the presence of meager or no immune response against newly emerged viruses. The success of vaccines and drugs depends on their low susceptibility to the formation of escape mutants in virus. Identification of excess, non-synonymous substitutions over synonymous ones is a main indicator of positive Darwinian selection in protein-coding genes of NIVs. The positive Darwinian selection operating on each site of proteins were inferred by computing ω, the ratio of the non-synonymous/synonymous substitutions [dN/dS (or) Ka/Ks], which was calculated by three different methods in terms of codon-based maximum likelihood, branch-site and empirical Bayesian methods under various models. Totally, nine sites from PB2, PB1, HA, M2 and NS1 are inferred as positively selected. The function for amino acid sites of NIVs proteins under positive selection are inferred by comparing the sites with experimentally determined functionally known amino acid sites. Completely 4 positively selected sites of PB1, HA and M2 are found to be involved in B-cell epitopes (BCEs). Interestingly, most of these sites are also involving in T-cell epitopes (TCEs). However, more sites under positive selection forces are involved in TCEs than those of BCEs. Amino acid sites engaged in both BCEs and TCEs should be measured as highly suitable targets, because these sites could induce the strong humoral and cellular immune responses against targets.</abstract>
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<topic>Natural selection</topic>
<topic>Amino acid function</topic>
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<dateIssued encoding="w3cdtf">2013-06-27</dateIssued>
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<identifier type="eISSN">1573-6857</identifier>
<identifier type="JournalID">10709</identifier>
<identifier type="IssueArticleCount">14</identifier>
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<number>141</number>
<caption>vol.</caption>
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<number>4-6</number>
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<start>143</start>
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