showing 9 related works from this author
Effect of mismatch repair on the mutation rate of bacteriophage ϕX174
2015
Viral mutation rates vary widely in nature, yet the mechanistic and evolutionary determinants of this variability remain unclear. Small DNA viruses mutate orders of magnitude faster than their hosts despite using host-encoded polymerases for replication, which suggests these viruses may avoid post-replicative repair. Supporting this, the genome of bacteriophage ϕX174 is completely devoid of GATC sequence motifs, which are required for methyl-directed mismatch repair in Escherichia coli . Here, we show that restoration of the randomly expected number of GATC sites leads to an eightfold reduction in the rate of spontaneous mutation of the phage, without severely impairing its replicative capa…
Delayed lysis confers resistance to the nucleoside analogue 5-fluorouracil and alleviates mutation accumulation in the single-stranded DNA bacterioph…
2014
ABSTRACT Rates of spontaneous mutation determine viral fitness and adaptability. In RNA viruses, treatment with mutagenic nucleoside analogues selects for polymerase variants with increased fidelity, showing that viral mutation rates can be adjusted in response to imposed selective pressures. However, this type of resistance is not possible in viruses that do not encode their own polymerases, such as single-stranded DNA viruses. We previously showed that serial passaging of bacteriophage ϕX174 in the presence of the nucleoside analogue 5-fluorouracil (5-FU) favored substitutions in the lysis protein E (P. Domingo-Calap, M. Pereira-Gomez, and R. Sanjuán, J. Virol. 86: 9640–9646, 2012, doi:10…
Mutation rate of bacteriophage ΦX174 modified through changes in GATC sequence context
2011
Bacteriophage ΦX174 has a relatively high mutation rate of 10⁻⁶ substitutions per nucleotide per strand copying. A thirty-fold reduction in the mutation rate was achieved by introducing seven GATC sequences in its genome. This motif allows for methyl-directed mismatch repair and is strongly avoided in nature by ΦX174 and other phages.
Selection for thermostability can lead to the emergence of mutational robustness in an RNA virus
2010
Mutational robustness has important evolutionary implications, yet the mechanisms leading to its emergence remain poorly understood. One possibility is selection acting on a correlated trait, as for instance thermostability (plastogenetic congruence). Here, we examine the correlation between mutational robustness and thermostability in experimental populations of the RNA bacteriophage Qβ. Thermostable viruses evolved after only six serial passages in the presence of heat shocks, and genome sequencing suggested that thermostability can be conferred by several alternative mutations. To test whether thermostable viruses have increased mutational robustness, we performed additional passages in …
Lamivudine/Adefovir Treatment Increases the Rate of Spontaneous Mutation of Hepatitis B Virus in Patients.
2016
The high levels of genetic diversity shown by hepatitis B virus (HBV) are commonly attributed to the low fidelity of its polymerase. However, the rate of spontaneous mutation of human HBV in vivo is currently unknown. Here, based on the evolutionary principle that the population frequency of lethal mutations equals the rate at which they are produced, we have estimated the mutation rate of HBV in vivo by scoring premature stop codons in 621 publicly available, full-length, molecular clone sequences derived from patients. This yielded an estimate of 8.7 × 10-5 spontaneous mutations per nucleotide per cell infection in untreated patients, which should be taken as an upper limit estimate becau…
Nucleoside Analogue Mutagenesis of a Single-Stranded DNA Virus: Evolution and Resistance
2012
ABSTRACT It has been well established that chemical mutagenesis has adverse fitness effects in RNA viruses, often leading to population extinction. This is mainly a consequence of the high RNA virus spontaneous mutation rates, which situate them close to the extinction threshold. Single-stranded DNA viruses are the fastest-mutating DNA-based systems, with per-nucleotide mutation rates close to those of some RNA viruses, but chemical mutagenesis has been much less studied in this type of viruses. Here, we serially passaged bacteriophage ϕX174 in the presence of the nucleoside analogue 5-fluorouracil (5-FU). We found that 5-FU was unable to trigger population extinction for the range of conce…
Seguint la pista del VIH: els estudis evolutius i la comprensió de la sida.
2013
El VIH o virus de la immunodefi ciencia humana te un gran impacte sanitari, social i economic; les terapies actuals permeten controlar la infeccio pero no s’ha trobat tractament guaridor ni vacuna efectiva. Per a aconseguir aquests objectius, ha de tenir-se en compte la gran variabilitat genetica i la rapida evolucio del VIH, associades, per exemple, a l’aparicio de variants de resistencia a farmacs o de canvis antigenics.
Experimental Evolution and Population Genetics of RNA Viruses
2009
Viral studies have contributed substantially to the field of experimental evolution during the last two decades. The rapid evolution of RNA viruses makes them especially suitable for investigating real-time evolution, while their small genomes facilitate the analysis of the genetic basis of evolutionary change. We review recent advances in RNA virus experimental evolution, focusing on genetic properties that differentiate them from DNA-based organisms, such as their high mutation rates, small genome sizes, low genetic robustness, and the predominance of antagonistic epistasis. We argue that these properties can explain many aspects of RNA virus evolution, including rapid evolution, marked f…
Genome Instability in DNA Viruses
2016
Genome instability generally refers to the appearance of a high frequency of mutations in a single genome, including point mutations, insertions/deletions, or major rearrangements. DNA viruses usually show greater genome stability than RNA viruses. However, recent genome-wide molecular evolution and experimental studies have shown that DNA viruses can exhibit rapid sequence changes that are often found in loci involved in dynamic host–virus interactions. In fact, DNA viruses are capable of promoting genome instability specifically at certain genes, thus boosting diversity wherein needed. We review some of the molecular mechanisms underlying genomic instability in prokaryotic and eukaryotic …