Abstract
The aim of this study was to estimate substitution rate and imprints of natural selection on parvovirus B19 genotype 1. Studied datasets included 137 near complete coding B19 genomes (positions 665 to 4851) for phylogenetic and substitution rate analysis and 146 and 214 partial genomes for selection analyses in open reading frames ORF1 and ORF2, respectively, collected 1973–2012 and including 9 newly sequenced isolates from Serbia. Phylogenetic clustering assigned majority of studied isolates to G1A. Nucleotide substitution rate for total coding DNA was 1.03 (0.6–1.27) x 10−4 substitutions/site/year, with higher values for analyzed genome partitions. In spite of the highest evolutionary rate, VP2 codons were found to be under purifying selection with rare episodic positive selection, whereas codons under diversifying selection were found in the unique part of VP1, known to contain B19 immune epitopes important in persistent infection. Analyses of overlapping gene regions identified nucleotide positions under opposite selective pressure in different ORFs, suggesting complex evolutionary mechanisms of nucleotide changes in B19 viral genomes.
Highlights
The aim of this study was to estimate substitution rate and imprints of natural selection on parvovirus B19 genotype 1
Human parvovirus B19 (B19) is a widespread member of the family Parvoviridae that causes a variety of clinical manifestations, from asymptomatic to persistent infection associated with different autoimmune diseases[1,2]
Average nucleotide distance in the whole analyzed near complete coding DNA (cDNA) dataset of 133 B19 genotype 1 isolates was 0.014, s.d. = 0.009
Summary
The aim of this study was to estimate substitution rate and imprints of natural selection on parvovirus B19 genotype 1. Studied datasets included 137 near complete coding B19 genomes (positions 665 to 4851) for phylogenetic and substitution rate analysis and 146 and 214 partial genomes for selection analyses in open reading frames ORF1 and ORF2, respectively, collected 1973–2012 and including 9 newly sequenced isolates from Serbia. B19 virions are nonenveloped icosahedral particles with a linear single-stranded DNA genome of approximately 5600 bp. Coding sequence of the B19 genome (≈4 .8 kb) is divided in two main open reading frames (ORFs), one encoding the nonstructural protein (NS1) and the other encoding both major VP2 and minor VP1 structural proteins[1,3]. Viremia declines with appearance of IgM antibodies against linear and conformational epitopes of viral capsid proteins VP1 and VP2, with the peak levels during the third weeks after infection. All genotypes have similar functional, structural and immunological characteristics and comprise the same serotype[15]
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