Document Detail

Genetic lesions associated with Muller's ratchet in an RNA virus.
MedLine Citation:
PMID:  8951375     Owner:  NLM     Status:  MEDLINE    
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 a severely debilitated clone suggests that very few mutations may be sufficient to drive FMDV near extinction. The results provide an account of the molecular basis of Muller's ratchet for an RNA virus, and insight into the types of genetic variants which populate the mutant spectra of FMDV quasispecies.
C Escarmís; M Dávila; N Charpentier; A Bracho; A Moya; E Domingo
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of molecular biology     Volume:  264     ISSN:  0022-2836     ISO Abbreviation:  J. Mol. Biol.     Publication Date:  1996 Nov 
Date Detail:
Created Date:  1997-01-02     Completed Date:  1997-01-02     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  2985088R     Medline TA:  J Mol Biol     Country:  ENGLAND    
Other Details:
Languages:  eng     Pagination:  255-67     Citation Subset:  IM    
Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Spain.
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MeSH Terms
Aphthovirus / genetics*
Cell Line
Extinction, Psychological
Nucleic Acid Conformation
Plaque Assay
RNA, Viral / analysis*
Reg. No./Substance:
0/RNA, Viral

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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