Abstract

Poxviruses are highly successful pathogens, known to infect a variety of hosts. The family Poxviridae includes Variola virus, the causative agent of smallpox, which has been eradicated as a public health threat but could potentially reemerge as a bioterrorist threat. The risk scenario includes other animal poxviruses and genetically engineered manipulations of poxviruses. Studies of orthologous gene sets have established the evolutionary relationships of members within the Poxviridae family. It is not clear, however, how variations between family members arose in the past, an important issue in understanding how these viruses may vary and possibly produce future threats. Using a newly developed poxvirus-specific tool, we predicted accurate gene sets for viruses with completely sequenced genomes in the genus Orthopoxvirus. Employing sensitive sequence comparison techniques together with comparison of syntenic gene maps, we established the relationships between all viral gene sets. These techniques allowed us to unambiguously identify the gene loss/gain events that have occurred over the course of orthopoxvirus evolution. It is clear that for all existing Orthopoxvirus species, no individual species has acquired protein-coding genes unique to that species. All existing species contain genes that are all present in members of the species Cowpox virus and that cowpox virus strains contain every gene present in any other orthopoxvirus strain. These results support a theory of reductive evolution in which the reduction in size of the core gene set of a putative ancestral virus played a critical role in speciation and confining any newly emerging virus species to a particular environmental (host or tissue) niche.

Highlights

  • Poxviruses are a family of viral pathogens known to infect a variety of organisms including insects, reptiles, birds and mammals

  • High-quality alignments can be generated using a subset of well-conserved genes shared between each subfamily, and these genes can be used to assess the evolutionary history for the whole Poxviridae family of viruses

  • The tree was inferred based on the amino acid alignment to minimize artifacts that arise from tree construction based on nucleic acid alignments of sequences with biased base compositions. (The family Poxviridae contains viruses with base compositions ranging from approximately 18% GC for entomopoxvirus strains to 64% GC for parapoxviruses and molluscum contagiosum virus.) This tree clearly delineates the two Poxviridae subfamilies, and shows the phylogenetic relationships that exist between the

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Summary

Introduction

Poxviruses are a family of viral pathogens known to infect a variety of organisms including insects, reptiles, birds and mammals. Based on some of these differences in host range, the Poxviridae family of viruses is subdivided into two subfamilies, the Chordopoxvirinae (ChPV), which infect vertebrates, and the Entomopoxvirinae, which infect insects. Each of these subfamilies is further subdivided into genera based on shared characteristics such as host range, morphology, antigenicity, and sequence similarity [2]. Host range represents one of the significant major phenotypic differences between members of the Poxviridae family [3], and there have been suggestions that one of the major evolutionary driving forces of this virus family has been co-speciation with their hosts [4,5]. Members of the Yatapoxvirus genus infect primate species [12,13]

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