0000000000349720
AUTHOR
Esteban Domingo
EVOLUTIONARY DYNAMICS OF FITNESS RECOVERY FROM THE DEBILITATING EFFECTS OF MULLER'S RATCHET.
The great adaptability shown by RNA viruses is a consequence of their high mutation rates. The evolution of fitness in a severely debilitated, clonal population of the nonsegmented ribovirus vesicular stomatitis virus (VSV) has been compared under five different demographic regimes, ranging from severe serial bottleneck passages (one virion) to large population passages (105 virions or more) under similar environmental conditions (cell culture type and temperature). No matter how small the bottleneck, the fitness of the evolved populations was always higher than the fitness of the starting population; this result is clearly different from that previously reported for viruses with higher fit…
Repeated transfer of small RNA virus populations leading to balanced fitness with infrequent stochastic drift
The population dynamics of RNA viruses have an important influence on fitness variation and, in consequence, on the adaptative potential and virulence of this ubiquitous group of pathogens. Earlier work with vesicular stomatitis virus showed that large population transfers were reproducibly associated with fitness increases, whereas repeated transfers from plaque to plaque (genetic bottlenecks) lead to losses in fitness. We demonstrate here that repeated five-plaque to five-plaque passage series yield long-term fitness stability, except for occasional stochastic fitness jumps. Repeated five-plaque passages regularly alternating with two consecutive large population transmissions did not cau…
RNA viruses: a bridge between life and artificial life
RNA viruses can be an adequate bridge between life and artificial life. Under experimental conditions the parameters that in last instance are responsible for the evolution of replicons resembling primitive life forms can be easily studied. One year of a RNA virus evolving may be equivalent to one million years of an evolving DNA-based entity. High mutation rates as well as very short life cycles permit the capability of observing evolutionary effects in the lifetime of a human observer. Another important feature of RNA viruses, functionally related to its mutation rate, is the genome length, which ranges between 3 and 30 Kb, probably the shortest lengths with the highest estimated mutation…
Gene encoding capsid protein VP1 of foot-and-mouth disease virus A quasispecies model of molecular evolution
A phylogenetic tree relating the VP1 gene of 15 isolates of foot-and-mouth disease virus (FMDV) of serotypes A, C, and O has been constructed. The most parsimonious tree shows that FMDV subtypes and isolates within subtypes constitute sets of related, nonidentical genomes, in agreement with a quasispecies mode of evolution of this virus. The average number of nucleotide replacements per site for all possible pairs of VP1 coding segments is higher among representatives of serotype A than serotype C or O. In comparing amino acid sequences, the values of dispersion index (variance/mean value) are greater than 1, with the highest values scored when all sequences are considered. This indicates a…
Fixation of mutations at the VP1 gene of foot-and-mouth disease virus. Can quasispecies define a transient molecular clock?
The number of nucleotide (nt) substitutions found in the VP1 gene (encoding viral capsid protein) between any two of 16 closely related isolates of foot-and-mouth disease virus (FMDV) has been quantified as a function of the time interval between isolations [Villaverde et al.,J. Mol. Biol. 204(1988)771-776]. One of them (isolate C-S12) includes some replacements found in isolates that preceded it and other replacements found in later isolates. The study has revealed alternating periods of rapid evolution and of relative genetic stability of VP1. During a defined period of acute disease, the rate of fixation of replacements at the VP1 coding segment was 6 × 10-3 substitutions per nt per year…
Genetic Variability and Antigenic Diversity of Foot-and-Mouth Disease Virus
Foot-and-mouth disease (FMD) is an acute systemic disease of cloven-hooved animals, including cattle, swine, sheep, and goats. Despite mortality rates being generally below 5%, FMD severely decreases livestock productivity and trade. It is considered the economically most important disease of farm animals. Near two thousand million doses of vaccine are used annually to try to control FMD, which, nevertheless, is enzootic in most South American and African countries, parts of Asia, the Middle East, and the south of Europe. The causative agent, foot-and-mouth disease virus (FMDV), is an aphthovirus of the family Picornaviridae, a historically important virus as it was the first recognized vir…
Evidence for Positive Selection in the Capsid Protein-Coding Region of the Foot-and-Mouth Disease Virus (FMDV) Subjected to Experimental Passage Regimens
We present sequence data from two genomic regions of foot-and-mouth disease virus (FMDV) subjected to several experimental passage regimens. Maximum-likelihood estimates of the nonsynonymous-to-synonymous rate ratio parameter (dN/dS) suggested the action of positive selection on some antigenic sites of the FMDV capsid during some experimental passages. These antigenic sites showed an accumulation of convergent amino acid replacements during massive serial cytolytic passages and also in persistent infections of FMDV in cell culture. This accumulation was most significant at the antigenic site A (the G-H loop of capsid VP1), which includes an Arg-Gly-Asp (RGD) cellular recognition motif. Our …
Genetic lesions associated with Muller's ratchet in an RNA virus
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 m…
Repetitive nucleotide sequencing of a dispensable DNA segment in a clonal population of African swine fever virus
Abstract Repetitive nucleotide sequencing of a dispensable genomic segment of a clonal population of African swine fever (ASF) virus has been carried out to estimate the mutant frequency to neutral alleles. Since no mutations have been detected in a total of 54026 nucleotides screened, the maximum mutant frequency is 5.5 × 10 −5 substitutions/nucleotide (95% confidence level). The result renders very unlikely the occurrence of hypermutational events during ASF virus DNA replication, at least within the selected DNA fragment.
Evolution of fitness in experimental populations of vesicular stomatitis virus
Abstract The evolution of fitness in experimental clonal populations of vesicular stomatitis virus (VSV) has been compared under different genetic (fitness of initial clone) and demographic (population dynamics) regimes. In spite of the high genetic heterogeneity among replicates within experiments, there is a clear effect of population dynamics on the evolution of fitness. Those populations that went through strong periodic bottlenecks showed a decreased fitness in competition experiments with wild type. Conversely, mutant populations that were transferred under the dynamics of continuous population expansions increased their fitness when compared with the same wild type. The magnitude of …