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Originally published in Science Express on 27 July 2006
Science 11 August 2006:
Vol. 313. no. 5788, pp. 807 - 812
DOI: 10.1126/science.1125134
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Research Articles

Genome Sequence Diversity and Clues to the Evolution of Variola (Smallpox) Virus

Joseph J. Esposito,1*{dagger} Scott A. Sammons,1* A. Michael Frace,1* John D. Osborne,1*{ddagger} Melissa Olsen-Rasmussen,1* Ming Zhang,1§ Dhwani Govil,1 Inger K. Damon,2 Richard Kline,2 Miriam Laker,2|| Yu Li,2 Geoffrey L. Smith,3 Hermann Meyer,4 James W. LeDuc,2 Robert M. Wohlhueter1

Comparative genomics of 45 epidemiologically varied variola virus isolates from the past 30 years of the smallpox era indicate low sequence diversity, suggesting that there is probably little difference in the isolates' functional gene content. Phylogenetic clustering inferred three clades coincident with their geographical origin and case-fatality rate; the latter implicated putative proteins that mediate viral virulence differences. Analysis of the viral linear DNA genome suggests that its evolution involved direct descent and DNA end-region recombination events. Knowing the sequences will help understand the viral proteome and improve diagnostic test precision, therapeutics, and systems for their assessment.

1 Biotechnology Core Facility Branch, Division of Scientific Resources, National Center for Preparedness, Detection, and Control of Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
2 Poxvirus and Rabies Branch, Division of Viral and Rickettsial Diseases, National Center for Zoonotic, Vector-Borne, and Enteric Diseases, Coordinating Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30329, USA.
3 Imperial College London, St. Mary's Campus, London, W2 1PG, UK.
4 Bundeswehr Institute of Microbiology, Munich, Germany 80937.

* These authors contributed equally to this work.

{ddagger} Present address: Northwestern University, Chicago, IL 60611, USA.

§ Present address: University of Goettingen, Goettingen, Germany 37077.

|| Present address: 324 North Kern Street, Ridgecrest, CA 93555, USA.

Unit designations pending agency reorganization.

{dagger} To whom correspondence should be addressed. E-mail: jesposito{at}cdc.gov

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From the Cover: On the origin of smallpox: Correlating variola phylogenics with historical smallpox records.
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GeneChip Resequencing of the Smallpox Virus Genome Can Identify Novel Strains: a Biodefense Application.
I. M. Sulaiman, K. Tang, J. Osborne, S. Sammons, and R. M. Wohlhueter (2007)
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