Genetic lesions associated with Muller's ratchet in an RNA virus

Journal of Molecular Biology
Cristina EscarmísE Domingo

Abstract

The molecular basis of Muller's ratchet has been investigated using the important animal pathogen foot-and-mouth disease virus (FMDV). Clones from two FMDV populations were subjected to serial plaque transfers (repeated bottleneck events) on host BHK-21 cells. Relative fitness losses were documented in 11 out of 19 clones tested. Small fitness gains were observed in three clones. One viral clone attained an extremely low plating efficiency, suggesting that accumulation of deleterious mutations had driven the virus near extinction. Nucleotide sequence analysis revealed unique genetic lesions in multiply transferred clones that had never been seen in FMDVs isolated in nature or subjected to massive infections in cell culture. In particular, a frequent internal polyadenylate extension has identified a mutational hot spot on the FMDV genome. Furthermore, amino acid residue substitutions in internal capsid sites which are severely restricted during FMDV evolution, amounted to half of capsid replacements in the transferred clones. In addition, a striking dominance of non-synonymous replacements fixed upon large population infections of FMDV was not observed upon serial plaque transfers. The nucleotide sequence of the entire genome of...Continue Reading

Citations

Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Samuel OjosnegrosEsteban Domingo
Aug 11, 2000·Evolution; International Journal of Organic Evolution·M de la PeñaA Moya
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Nov 17, 2009·PLoS Pathogens·Celia PeralesEsteban Domingo

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