The cost of replication fidelity in human immunodeficiency virus type 1

Furió, Victoria; Moya, Andrés; Sanjuán, Rafael

doi:10.1098/rspb.2006.3732

Cited by 38 publications

(40 citation statements)

References 41 publications

(46 reference statements)

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“…Given the potential for pleiotropy among diverse gene products that has been revealed by recent genomic approaches (Paaby and Rockman, 2013;Solovieff et al, 2013), there remains a clear need for experiments testing whether mutation rate modifiers themselves have direct selective effects. Limited studies, for example, have shown that enhanced replication fidelity (lower mutation rate) may decrease replication rate in some viruses and thus be directly costly (Furio et al, 2005;Furio et al, 2007). A recent study in Pseudomonas aeruginosa also showed that a mutS mutator allele can provide inherent resistance to oxidative stress and so could have a direct fitness benefit in certain environments (Torres- Barceló et al, 2013).…”

Section: Why Aren't All Asexually Reproducing Populations Fixed For Mmentioning

confidence: 99%

Experimental evolution and the dynamics of genomic mutation rate modifiers

Raynes

Sniegowski

2014

Heredity

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Because genes that affect mutation rates are themselves subject to mutation, mutation rates can be influenced by natural selection and other evolutionary forces. The population genetics of mutation rate modifier alleles has been a subject of theoretical interest for many decades. Here, we review experimental contributions to our understanding of mutation rate modifier dynamics. Numerous evolution experiments have shown that mutator alleles (modifiers that elevate the genomic mutation rate) can readily rise to high frequencies via genetic hitchhiking in non-recombining microbial populations. Whereas these results certainly provide an explanatory framework for observations of sporadically high mutation rates in pathogenic microbes and in cancer lineages, it is nonetheless true that most natural populations have very low mutation rates. This raises the interesting question of how mutator hitchhiking is suppressed or its phenotypic effect reversed in natural populations. Very little experimental work has addressed this question; with this in mind, we identify some promising areas for future experimental investigation.

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Section: Why Aren't All Asexually Reproducing Populations Fixed For Mmentioning

confidence: 99%

Experimental evolution and the dynamics of genomic mutation rate modifiers

Raynes

Sniegowski

2014

Heredity

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“…Elevated mutation frequencies are associated with human pathologies such as cancer and premature aging (7,8). Large increases in accuracy, on the other hand, can be energetically costly (9) and also lead to decreased fitness.…”

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confidence: 99%

Optimization of DNA polymerase mutation rates during bacterial evolution

Loh

Salk

Loeb

2009

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

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Mutation rate is an important determinant of evolvability. The optimal mutation rate for different organisms during evolution has been modeled in silico and tested in vivo, predominantly through pairwise comparisons. To characterize the fitness landscape across a broad range of mutation rates, we generated a panel of 66 DNA polymerase I mutants in Escherichia coli with comparable growth properties, yet with differing DNA replication fidelities, spanning 10 3 -fold higher and lower than that of wild type. These strains were competed for 350 generations in six replicate cultures in two different environments. A narrow range of mutation rates, 10-to 47-fold greater than that of wild type, predominated after serial passage. Mutants exhibiting higher mutation rates were not detected, nor were wild-type or antimutator strains. Winning clones exhibited shorter doubling times, greater maximum culture densities, and a growth advantages in pairwise competition relative to their precompetition ancestors, indicating the acquisition of adaptive phenotypes. To investigate the basis for mutator selection, we undertook a large series of pairwise competitions between mutator and wildtype strains under conditions where, in most cases, one strain completely overtook the culture within 18 days. Mutators were the most frequent winners but wild-type strains were also observed winning, suggesting that the competitive advantage of mutators is due to a greater probability of developing selectably advantageous mutations rather than from an initial growth advantage conferred by the polymerase variant itself. Our results indicate that under conditions where organism fitness is not yet maximized for a particular environment, competitive adaptation may be facilitated by enhanced mutagenesis.adaptation | competition | fidelity | mutator M utation rates in organisms reflect the need for accuracy to maintain critical genetic information and the requirement for flexibility to adapt to environmental changes. In eukaryotic and prokaryotic cells, spontaneous mutations occur infrequently-less than once per billion bases copied (1). A departure from this norm can be detrimental to an individual and to a population as a whole. Increased mutation rates in viruses (2, 3) and bacteria (4, 5) can lead to decreased fitness and ultimately to extinction (6). Elevated mutation frequencies are associated with human pathologies such as cancer and premature aging (7,8). Large increases in accuracy, on the other hand, can be energetically costly (9) and also lead to decreased fitness.Although low mutation rates benefit populations in stable environments, higher mutation rates favor adaptation. Evolution has derived mechanisms for transient changes in mutation rates to circumvent the narrow restriction imposed by the high fidelity required for long-term survival. Mutagenesis is induced by bacteria during times of stress (10), and the mammalian immune system relies on targeted hypermutation to respond to new pathogens (11). In experiments where populations of bacte...

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“…rspb.royalsocietypublishing.org Proc R Soc B 280: 20122047 that this has been explicitly studied in the context of viruses [29,30]. The basic principles applying to prokaryotes and eukaryotes do not directly apply to viruses because selection acts differently in viruses.…”

Section: Discussionmentioning

confidence: 99%

Viral mutation rates: modelling the roles of within-host viral dynamics and the trade-off between replication fidelity and speed

2013

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Many viruses, particularly RNA viruses, mutate at a very high rate per genome per replication. One possible explanation is that high mutation rates are selected to meet the challenge of fluctuating environments, including the host immune response. Alternatively, recent studies argue that viruses evolve under a trade-off between replication speed and fidelity such that fast replication is selected, and, along with it, high mutation rates. Here, in addition to these factors, we consider the role of viral lifehistory properties: namely, the within-host dynamics of viruses resulting from their interaction with the host. We develop mathematical models incorporating factors occurring within and between hosts, including deleterious and advantageous mutations, host death owing to virulence and clearance of viruses by the host. Beneficial mutations confer both a within-host and a transmission advantage. First, we find that advantageous mutations have only a weak effect on the optimal genomic mutation rate. Second, viral life-history properties have a large effect on the mutation rate. Third, when the speed-fidelity trade-off is included, there can be two locally optimal mutation rates. Our analysis provides a way to consider how life-history properties combine with biochemical trade-offs to shape mutation rates.

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The cost of replication fidelity in human immunodeficiency virus type 1

Cited by 38 publications

References 41 publications

Experimental evolution and the dynamics of genomic mutation rate modifiers

Experimental evolution and the dynamics of genomic mutation rate modifiers

Optimization of DNA polymerase mutation rates during bacterial evolution

Viral mutation rates: modelling the roles of within-host viral dynamics and the trade-off between replication fidelity and speed

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