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Published Online July 27, 2006
Science DOI: 10.1126/science.1125134

Research Articles

Submitted on January 19, 2006
Accepted on May 30, 2006

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

Joseph J. Esposito 1*, Scott A. Sammons 1, A. Michael Frace 1, John D. Osborne 2, Melissa Olsen-Rasmussen 1, Ming Zhang 3, Dhwani Govil 1, Inger K. Damon 4, Richard Kline 5, Miriam Laker 6, Yu Li 4, Geoffrey L. Smith 7, Hermann Meyer 8, James W. LeDuc 9, Robert M. Wohlhueter 1

1 Biotechnology Core Facility Branch, Division of Scientific Resources, National Center for Preparedness, Detection, and Control of Infectious Diseases
2 Biotechnology Core Facility Branch, Division of Scientific Resources, National Center for Preparedness, Detection, and Control of Infectious Diseases; Present address: Northwestern University, Chicago, IL 60611, USA.
3 Biotechnology Core Facility Branch, Division of Scientific Resources, National Center for Preparedness, Detection, and Control of Infectious Diseases; Present address: University of Goettingen, Goettingen, Germany 37077
4 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.
5 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.
6 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; Present address: 324 North Kern Street, Ridgecrest, CA 93555, USA.
7 Imperial College London, St. Mary's Campus, London, W2 1PG, UK.
8 Bundeswehr Institute of Microbiology, Munich, Germany 80937
9 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.

* To whom correspondence should be addressed.
Joseph J. Esposito , E-mail: jesposito{at}cdc.gov

Comparative genomics of 45 epidemiologically varied Variola virus isolates from the last 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.


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