Efficient escape from local optima in a highly rugged fitness landscape by evolving RNA virus populations

Cervera, Héctor; Lalić, Jasna; Elena, Santiago F.

doi:10.1098/rspb.2016.0984

Cited by 19 publications

(21 citation statements)

References 39 publications

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“…We had anticipated that insertions in the virus genome might have evolutionary benefits by increasing mutational robustness, if they coded functional sequences that result in functional redundancy. Theoretically, redundancy may contribute to flattening off the typically rugged fitness landscape of RNA viruses (Cervera et al 2016), thus allowing for a more efficient exploration of distant regions of the fitness landscape without the need of crossing fitness valleys (Van Nimwegen 2006). Surprisingly, our results suggest that no such relationship exists, and that functional or non-functional increases in the size of the coding genome decrease the mutational robustness, even for the case of duplicated genes.…”

Section: Discussionmentioning

confidence: 71%

Going, going, gone: predicting the fate of genomic insertions in plant RNA viruses

et al. 2018

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Horizontal gene transfer is common among viruses, while they also have highly compact genomes and tend to lose artificial genomic insertions rapidly. Understanding the stability of genomic insertions in viral genomes is therefore relevant for explaining and predicting their evolutionary patterns. Here, we revisit a large body of experimental research on a plant RNA virus, tobacco etch potyvirus (TEV), to identify the patterns underlying the stability of a range of homologous and heterologous insertions in the viral genome. We obtained a wide range of estimates for the recombination rate-the rate at which deletions removing the insertion occur-and these appeared to be independent of the type of insertion and its location. Of the factors we considered, recombination rate was the best predictor of insertion stability, although we could not identify the specific sequence characteristics that would help predict insertion instability. We also considered experimentally the possibility that functional insertions lead to higher mutational robustness through increased redundancy. However, our observations suggest that both functional and non-functional increases in genome size decreased the mutational robustness. Our results therefore demonstrate the importance of recombination rates for predicting the long-term stability and evolution of viral RNA genomes and suggest that there are unexpected drawbacks to increases in genome size for mutational robustness.

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Section: Discussionmentioning

confidence: 71%

Going, going, gone: predicting the fate of genomic insertions in plant RNA viruses

et al. 2018

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“…The relationships between mutation rates, quasispecies, robustness, and evolvability of RNA viruses are discussed in detail in numerous publications (487,(515)(516)(517)(518)(519)(520)(521)(522)(523)(524)(525)(526). This problem is closely related to the emergence/reemergence of pathogenic viruses, which has recently become a hot topic (527)(528)(529)(530)(531)(532).…”

Section: Robustness Resilience and Evolvability Of Viral Rna Genomesmentioning

confidence: 99%

Emergency Services of Viral RNAs: Repair and Remodeling

Agol

Gmyl

2018

Microbiol Mol Biol Rev

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Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.

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“…Another important factor influencing fitness trajectories is the underlying fitness landscape ( Clune et al. 2008 ; Cervera, Lalić, and Elena 2016a ), which determines the most accessible fitness peak for each genome. Populations can be trapped in quasi-mutation-selection balance on these suboptimal fitness peaks for a very long time ( Jain and Krug 2007 ; Cervera, Lalić, and Elena 2016b ), such that the global maximum is not always found before a new perturbation affects the population.…”

Section: Introductionmentioning

confidence: 99%

Differences in adaptive dynamics determine the success of virus variants that propagate together

et al. 2018

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Virus fitness is a complex parameter that results from the interaction of virus-specific characters (e.g. intracellular growth rate, adsorption rate, virion extracellular stability, and tolerance to mutations) with others that depend on the underlying fitness landscape and the internal structure of the whole population. Individual mutants usually have lower fitness values than the complex population from which they come from. When they are propagated and allowed to attain large population sizes for a sufficiently long time, they approach mutation-selection equilibrium with the concomitant fitness gains. The optimization process follows dynamics that vary among viruses, likely due to differences in any of the parameters that determine fitness values. As a consequence, when different mutants spread together, the number of generations experienced by each of them prior to co-propagation may determine its particular fate. In this work we attempt a clarification of the effect of different levels of population diversity in the outcome of competition dynamics. To this end, we analyze the behavior of two mutants of the RNA bacteriophage Qβ that co-propagate with the wild-type virus. When both competitor viruses are clonal, the mutants rapidly outcompete the wild type. However, the outcome in competitions performed with partially optimized virus populations depends on the distance of the competitors to their clonal origin. We also implement a theoretical population dynamics model that describes the evolution of a heterogeneous population of individuals, each characterized by a fitness value, subjected to subsequent cycles of replication and mutation. The experimental results are explained in the framework of our theoretical model under two non-excluding, likely complementary assumptions: (1) The relative advantage of both competitors changes as populations approach mutation-selection equilibrium, as a consequence of differences in their growth rates and (2) one of the competitors is more robust to mutations than the other. The main conclusion is that the nearness of an RNA virus population to mutation-selection equilibrium is a key factor determining the fate of particular mutants arising during replication.

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Efficient escape from local optima in a highly rugged fitness landscape by evolving RNA virus populations

Cited by 19 publications

References 39 publications

Going, going, gone: predicting the fate of genomic insertions in plant RNA viruses

Going, going, gone: predicting the fate of genomic insertions in plant RNA viruses

Emergency Services of Viral RNAs: Repair and Remodeling

Differences in adaptive dynamics determine the success of virus variants that propagate together

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