Abstract
We report a major improvement to the assembly of published short read sequencing data from an ancient variola virus (VARV) genome by the removal of contig-capping sequencing tags and manual searches for gap-spanning reads. The new assembly, together with camelpox and taterapox genomes, permitted new dates to be calculated for the last common ancestor of all VARV genomes. The analysis of recently sequenced VARV-like cowpox virus genomes showed that single nucleotide polymorphisms (SNPs) and amino acid changes in the vaccinia virus (VACV)-Cop-O1L ortholog, predicted to be associated with VARV host specificity and virulence, were introduced into the lineage before the divergence of these viruses. A comparison of the ancient and modern VARV genome sequences also revealed a measurable drift towards adenine + thymine (A + T) richness.
Highlights
Smallpox, which is caused by the poxvirus variola virus (VARV) [1], was declared eradicated almost 40 years ago, following a massive worldwide vaccination campaign [2,3]
VARV and vaccinia virus (VACV), which was used as a live vaccine, belong to the Orthopoxvirus genus within the Poxviridae family and have linear dsDNA genomes of approximately 200 kb
We found a block of single nucleotide polymorphisms (SNPs) in the O1L gene with the BBB search parameter “find position of nucleotides that are identical in VARV + CMLV + TATV but different in all CPXVs and
Summary
Smallpox, which is caused by the poxvirus variola virus (VARV) [1], was declared eradicated almost 40 years ago, following a massive worldwide vaccination campaign [2,3]. Not all are yet officially recognized, these likely fall into at least 18 genera When these viruses are aligned, the highest synteny and DNA sequence identity is found within a central core region of approximately 80 to 100 kb, with a gene density averaging approximately one per kb. Outside of this core, the genes, which mostly encode host range and virulence factors and are not present in all viruses, are frequently rearranged and have significantly lower levels of DNA and amino acid (aa) conservation than genes in the core region. When different sets of genes are compared for a given group of viruses, it is not uncommon to observe significantly different levels of conservation because core genes are more highly conserved [12]
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