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Journal of Virology, May 2008, p. 4429-4440, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02354-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Calibration of Multiple Poliovirus Molecular Clocks Covering an Extended Evolutionary Range{triangledown} ,{dagger}

Jaume Jorba,* Ray Campagnoli, Lina De, and Olen Kew

Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 30333

Received 31 October 2007/ Accepted 7 February 2008

We have calibrated five different molecular clocks for circulating poliovirus based upon the rates of fixation of total substitutions (Kt), synonymous substitutions (Ks), synonymous transitions (As), synonymous transversions (Bs), and nonsynonymous substitutions (Ka) into the P1/capsid region (2,643 nucleotides). Rates were determined over a 10-year period by analysis of sequences of 31 wild poliovirus type 1 isolates representing a well-defined phylogeny derived from a common imported ancestor. Similar rates were obtained by linear regression, the maximum likelihood/single-rate dated-tip method, and Bayesian inference. The very rapid Kt [(1.03 ± 0.10) x 10–2 substitutions/site/year] and Ks [(1.00 ± 0.08) x 10–2] clocks were driven primarily by the As clock [(0.96 ± 0.09) x 10–2], the Bs clock was ~10-fold slower [(0.10 ± 0.03) x 10–2], and the more stochastic Ka clock was ~30-fold slower [(0.03 ± 0.01) x 10–2]. Nonsynonymous substitutions at all P1/capsid sites, including the neutralizing antigenic sites, appeared to be constrained by purifying selection. Simulation of the evolution of third-codon positions suggested that saturation of synonymous transitions would be evident at 10 years and complete at ~65 years of independent transmission. Saturation of synonymous transversions was predicted to be minimal at 20 years and incomplete at 100 years. The rapid evolution of the Kt, Ks, and As clocks can be used to estimate the dates of divergence of closely related viruses, whereas the slower Bs and Ka clocks may be used to explore deeper evolutionary relationships within and across poliovirus genotypes.

* Corresponding author. Mailing address: Polio and Picornavirus Laboratory Branch, G-10, Division of Viral Diseases, National Center for Immunization and Respiratory Diseases, Centers for Disease Control and Prevention, Atlanta, GA 30333. Phone: (404) 639-4296. Fax: (404) 639-4011. E-mail: JJorba{at}cdc.gov

{triangledown} Published ahead of print on 20 February 2008.

{dagger} Supplemental material for this article may be found at http://jvi.asm.org/.

Journal of Virology, May 2008, p. 4429-4440, Vol. 82, No. 9
0022-538X/08/$08.00+0     doi:10.1128/JVI.02354-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.



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