title: Prediction of steps in the evolution of variola virus host range.
abstract: Variola virus, the agent of smallpox, has a severely restricted host range (humans) but a devastatingly high mortality rate. Although smallpox has been eradicated by a World Health Organization vaccination program, knowledge of the evolutionary processes by which human super-pathogens such as variola virus arise is important. By analyzing the evolution of variola and other closely related poxviruses at the level of single nucleotide polymorphisms we detected a hotspot of genome variation within the smallpox ortholog of the vaccinia virus O1L gene, which is known to be necessary for efficient replication of vaccinia virus in human cells. These mutations in the variola virus ortholog and the subsequent loss of the functional gene from camelpox virus and taterapox virus, the two closest relatives of variola virus, strongly suggest that changes within this region of the genome may have played a key role in the switch to humans as a host for the ancestral virus and the subsequent host-range restriction that must have occurred to create the phenotype exhibited by smallpox.
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Chad
authors.initials: C
authors.lastname: Smithson
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Alex
authors.initials: A
authors.lastname: Purdy
authors.affiliation: Department of Molecular Genetics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Verster
authors.affiliation: Department of Biochemistry and Microbiology, University of Victoria, Victoria, British Columbia, Canada.
authors.forename: Chris
authors.initials: C
authors.lastname: Upton
mesh_terms: D000596:Amino Acids / Q000737:chemistry; D004279:DNA, Viral / Q000235:genetics; D019143:Evolution, Molecular; D005814:Genes, Viral; D014644:Genetic Variation; D016678:Genome; D016679:Genome, Viral; D058507:Host Specificity / Q000235:genetics; D006801:Humans; D009154:Mutation; D010802:Phylogeny; D020641:Polymorphism, Single Nucleotide; D011212:Poxviridae / Q000235:genetics; D014616:Vaccinia virus / Q000235:genetics; D012901:Variola virus / Q000235:genetics*
chemical_list: D000596:Amino Acids; D004279:DNA, Viral