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Journal of Virology, September 2002, p. 8675-8681, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8675-8681.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Modeling Viral Genome Fitness Evolution Associated with Serial Bottleneck Events: Evidence of Stationary States of Fitness

Ester Lázaro,1 Cristina Escarmís,2 Esteban Domingo,1,2* and Susanna C. Manrubia1

Centro de Astrobiología (CSIC-INTA), 28850 Torrejón de Ardoz, Madrid,1 Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain2

Received 4 February 2002/ Accepted 3 June 2002

Evolution of fitness values upon replication of viral populations is strongly influenced by the size of the virus population that participates in the infections. While large population passages often result in fitness gains, repeated plaque-to-plaque transfers result in average fitness losses. Here we develop a numerical model that describes fitness evolution of viral clones subjected to serial bottleneck events. The model predicts a biphasic evolution of fitness values in that a period of exponential decrease is followed by a stationary state in which fitness values display large fluctuations around an average constant value. This biphasic evolution is in agreement with experimental results of serial plaque-to-plaque transfers carried out with foot-and-mouth disease virus (FMDV) in cell culture. The existence of a stationary phase of fitness values has been further documented by serial plaque-to-plaque transfers of FMDV clones that had reached very low relative fitness values. The statistical properties of the stationary state depend on several parameters of the model, such as the probability of advantageous versus deleterious mutations, initial fitness, and the number of replication rounds. In particular, the size of the bottleneck is critical for determining the trend of fitness evolution.

* Corresponding author. Mailing address: Centro de Biología Molecular "Severo Ochoa" (CSIC-UAM), Universidad Autónoma de Madrid, Cantoblanco, 28049 Madrid, Spain. Phone: 34-91 3978485. Fax: 34-91 3974799. E-mail: edomingo{at}cbm.uam.es.

Journal of Virology, September 2002, p. 8675-8681, Vol. 76, No. 17
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.17.8675-8681.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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