Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations.

Pathak, Vinay K.; Temin, Howard M.

doi:10.1073/pnas.87.16.6019

Cited by 256 publications

(210 citation statements)

References 27 publications

(17 reference statements)

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“…Likewise, certain RTs can jump on a template with direct repeats, for example, in retroviruses (Pathak and Temin, 1990). RT jumping between direct repeats leads to a duplication or deletion depending on the jump direction.…”

Section: Evolution Of Sinesmentioning

confidence: 99%

Origin and evolution of SINEs in eukaryotic genomes

2011

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Section: Evolution Of Sinesmentioning

confidence: 99%

Origin and evolution of SINEs in eukaryotic genomes

2011

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“…Retroviruses, in particular human immunodeficiency virus type 1 (HIV-1), mutate and recombine at high rates (10 Ϫ4 misincorporations per nucleotide copied) (34)(35)(36). Rapid genetic variation, together with the short replication time of HIV-1, generates complex and dynamic mutant swarms termed viral quasispecies (28,40,46).…”

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confidence: 99%

Few Mutations in the 5′ Leader Region Mediate Fitness Recovery of Debilitated Human Immunodeficiency Type 1 Viruses

Yuste

Bordería

Domingo

et al. 2005

J Virol

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Repeated bottleneck passages of RNA viruses result in fitness losses due to the accumulation of deleterious mutations. In contrast, repeated transfers of large virus populations result in exponential fitness increases. Human immunodeficiency virus type 1 (HIV-1) manifested a drastic fitness loss after a limited number of plaque-to-plaque transfers in MT-4 cells. An analysis of the mutations associated with fitness loss in four debilitated clones revealed mutation frequencies in gag that were threefold higher than those in env. We now show an increase in the fitness of the debilitated HIV-1 clones by repeated passages of large populations. An analysis of the entire genomic nucleotide sequences of these populations showed that few mutations, from two to seven per clone, mediated fitness recovery. Eight of the 20 mutations affected coding regions, mainly by the introduction of nonsynonymous mutations (75%). However, most of the mutations accumulated during fitness recovery (12 of 20) were located in the 5 untranslated leader region of the genome, and more specifically, in the primer binding site (PBS) loop. Two of the viruses incorporated the same mutation in the primer activation signal in the PBS loop, which is critical for the tRNA 3Lys -mediated initiation of reverse transcription. Moreover, 25% of the mutations observed were reversions. This fact, together with the presence of a large proportion of nonsynonymous replacements, may disclose the operation, during large population passages, of strong positive selection for optimal HIV-1 replication, which seems to be primarily affected by binding of the tRNA to the PBS and the initiation of reverse transcription.

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“…Considerable data now document the extensive genetic variability and potential for rapid evolution of RNA viruses (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19). The molecular basis for this variation is extremely high mutation frequencies per average site in RNA virus genomes (ranging between 10-3 and 10-6 and usually of the order of 10' to .…”

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confidence: 99%

High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus.

Torre

Giachetti

Semler

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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We employed independent clones of a temperature-sensitive mutant of type 1 poliovirus, to quantitate the frequency of specific U -+ C transitions at nucleotide 5310, within the genomic region encoding polypeptide 3AB, which is involved in the initiation ofRNA replication.Only this U --C base substitution restores the wild-type phenotypic ability to form plaques at 39C; the other two base substitutions at this site are lethal. The observed frequency of this specific transition averaged 2 x i0S, and all revertant viruses forming plaques at39°C contained the expected cytidine at nucleotide 5310. Incredibly, only 3 of 10 revertants exhibited this one specific U --C transition whereas 7 of 10 exhibited this same transition plus four additional base substitutions that precisely reverted temperature-sensitive 3AB-310/4 to wildtype poliovirus sequence (these latter four mutations had been introduced into 3AB-310/4 as silent third base mutations to provide new restriction sites in infectious cDNAs). No other mutations were detected in this polypeptide 3AB domain in either the single-base or the precise 5-base revertants. No intermediates were seen; all revertants exhibited either the single U --C transition at nucleotide 5310 or the same transition plus four precise reversions to the wild-type sequence at sites 8, 11, 43, and 46 bases distant from nucleotide 5310. Similar results were obtained after transfection of cDNAderived transcripts. We discuss possible mechaniss for our data. These include (but may not be limited to) error-prone polymerase activity, sequential RNA recombination events joining independent mutations, or some unusual RNA editing process.Considerable data now document the extensive genetic variability and potential for rapid evolution of RNA viruses (1-19). The molecular basis for this variation is extremely high mutation frequencies per average site in RNA virus genomes (ranging between 10-3 and 10-6 and usually of the order of 10' to 10-5). Such high mutation frequencies dictate that even clones of RNA viruses are not homogeneous populations but consist of complex "mutant swarms" or "quasispecies" populations (20)(21)(22)(23)(24)(25)(26). By virtue of their extreme heterogeneity, quasispecies populations can adapt rapidly to new environments by selection of variants preexisting within the population. Some very low polymerase error values have been reported for poliovirus. Thus, Parvin et al. (27) have estimated a poliovirus mutation rate of <10-6 per site for viable neutral or quasineutral mutants of poliovirus.A similar low error frequency of 2.5 x 10-6 was estimated for the reversion of a poliovirus amber mutant (28). In contrast, frequencies of resistance to monoclonal antibody neutralization for poliovirus are in the range 10-3 to 10-5 base substitutions per site (29,30). In vitro measurements of poliovirus polymerase error frequencies (31) and the mutation frequency of poliovirus type 1 to a high degree of resistance to guanidine indicated specific single-site mutation frequencies...

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Broad spectrum of in vivo forward mutations, hypermutations, and mutational hotspots in a retroviral shuttle vector after a single replication cycle: substitutions, frameshifts, and hypermutations.

Cited by 256 publications

References 27 publications

Origin and evolution of SINEs in eukaryotic genomes

Origin and evolution of SINEs in eukaryotic genomes

Few Mutations in the 5′ Leader Region Mediate Fitness Recovery of Debilitated Human Immunodeficiency Type 1 Viruses

High frequency of single-base transitions and extreme frequency of precise multiple-base reversion mutations in poliovirus.

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