Topological features of rugged fitness landscapes in sequence space

Kondrashov, D.A.; Kondrashov, Fyodor A.

doi:10.1016/j.tig.2014.09.009

Cited by 101 publications

(110 citation statements)

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“…Recent data from bacterial, viral and eukaryotic systems show that epistasis is pervasive and that it might have an impact on resistance evolution [107][108][109] .…”

Section: Clonal Interferencementioning

confidence: 99%

“…From the left-hand side of the figure: resistant genetic variants generally have lower fitness than the susceptible parent, and in the absence of drug selection or of compensatory evolution, will gradually be lost from the population 39,40 (the ordering of the thick and thin arrows is not important). Multiple different mutant variants will frequently arise in a population, and the enrichment of specific successful variants will be determined by their relative fitness, the effects of clonal interference on competition between variants 91,92,95 and the effects of epistasis on the expression of mutant phenotypes 107,109 . The multiple parallel arrows indicate that the population of competing cells or organisms may contain many genetic variants, with some being driven to extinction and newer variants arising, before one or a few dominant cells or organisms finally approach fixation in the population 70,89 .…”

Section: Compensatory Evolutionmentioning

confidence: 99%

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Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms

2015

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Drug therapy has a crucial role in the treatment of viral, bacterial, fungal and protozoan infections, as well as the control of human cancer. The success of therapy is being threatened by the increasing prevalence of resistance. We examine and compare mechanisms of drug resistance in these diverse biological systems (using HIV and Plasmodium falciparum as examples of viral and protozoan pathogens, respectively) and discuss how factors — such as mutation rates, fitness effects of resistance, epistasis and clonal interference — influence the evolutionary trajectories of drug-resistant clones. We describe commonalities and differences related to resistance development that could guide strategies to improve therapeutic effectiveness and the development of a new generation of drugs.

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“…Recent data from bacterial, viral and eukaryotic systems show that epistasis is pervasive and that it might have an impact on resistance evolution [107][108][109] .…”

Section: Clonal Interferencementioning

confidence: 99%

Section: Compensatory Evolutionmentioning

confidence: 99%

Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms

2015

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“…However, this is not so. There is a progressive understanding of the importance of interactions within a genome, which are collectively referred to as epistasis [10][11][12][13]. Under epistasis, the SPFL is affected by genetic changes elsewhere in the genome.…”

Section: Causes Of Changementioning

confidence: 99%

“…It has been argued, for example, that the ancestral alleles found to be pathogenic in humans cannot be owing to adaptation of humans to a novel environment, as the phenotypes resulting from them are not reminiscent of ancestral ones [62]. Conversely, epistasis is expected to arise as an epiphenomenon of a wide range of biological processes [68], and its high prevalence is underscored by recently accumulating experimental data, including empirical data on interactions, limitations on the order in which substitutions may proceed, and repeatability of substitution paths in experimental evolution [11,13].…”

Section: Causes Of Changementioning

confidence: 99%

Changing preferences: deformation of single position amino acid fitness landscapes and evolution of proteins

Bazykin

2015

Biol. Lett.

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The fitness landscape-the function that relates genotypes to fitness-and its role in directing evolution are a central object of evolutionary biology. However, its huge dimensionality precludes understanding of even the basic aspects of its shape. One way to approach it is to ask a simpler question: what are the properties of a function that assigns fitness to each possible variant at just one particular site-a single position fitness landscape-and how does it change in the course of evolution? Analyses of genomic data from multiple species and multiple individuals within a species have proved beyond reasonable doubt that fitness functions of positions throughout the genome do themselves change with time, thus shaping protein evolution. Here, I will briefly review the literature that addresses these dynamics, focusing on recent genome-scale analyses of fitness functions of amino acid sites, i.e. vectors of fitnesses of 20 individual amino acid variants at a given position of a protein.The set of amino acids that confer high fitness at a particular position changes with time, and the rate of this change is comparable with the rate at which a position evolves, implying that this process plays a major role in evolutionary dynamics. However, the causes of these changes remain largely unclear.

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“…While it is easy to imagine some forms of epistasis that would cause reversion rates to decrease over time, evolutionary dynamics on high-dimensional fitness landscapes can have many counterintuitive properties (Conrad 1990;Gavrilets 1997;Carneiro and Hartl 2010;McCandlish et al 2013McCandlish et al , 2015bKondrashov and Kondrashov 2015). Here we undertake a rigorous mathematical investigation into the relationship between the rate of reversion and the presence of epistasis, for arbitrary fitness landscapes.…”

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confidence: 99%

Epistasis and the Dynamics of Reversion in Molecular Evolution

2016

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Recent studies of protein evolution contend that the longer an amino acid substitution is present at a site, the less likely it is to revert to the amino acid previously occupying that site. Here we study this phenomenon of decreasing reversion rates rigorously and in a much more general context. We show that, under weak mutation and for arbitrary fitness landscapes, reversion rates decrease with time for any site that is involved in at least one epistatic interaction. Specifically, we prove that, at stationarity, the hazard function of the distribution of waiting times until reversion is strictly decreasing for any such site. Thus, in the presence of epistasis, the longer a particular character has been absent from a site, the less likely the site will revert to its prior state. We also explore several examples of this general result, which share a common pattern whereby the probability of having reverted increases rapidly at short times to some substantial value before becoming almost flat after a few substitutions at other sites. This pattern indicates a characteristic tendency for reversion to occur either almost immediately after the initial substitution or only after a very long time.KEYWORDS weak mutation; fitness landscape; entrenchment; reversible Markov chain I N the context of evolutionary theory, reversion describes a population that returns to an ancestral character state (Porter and Crandall 2003). While many early (Dollo 1893;Muller 1939;Simpson 1953;Gould 1970) and more recent (Teotónio and Rose 2001;Collin and Miglietta 2008;Bridgham et al. 2009;Tan et al. 2011) discussions of reversion consider an environmental change that confers a selective advantage to an ancestral phenotype, reversion may also occur at the level of nucleic acids or protein sequences, with evolution proceeding under long-term purifying selection (Kimura 1983). Such reversions occur both because of the strictly limited number of character states (four possible nucleotides or 20 possible amino acids, Jukes and Cantor 1969) and because selection on molecular function may constrain a given position to only a subset of these possible character states (Rokas and Carroll 2008;Breen et al. 2012).It has long been hypothesized that epistatic interactions should lower the rate of reversion, rendering evolution effectively irreversible (Muller 1918(Muller , 1939. This issue has been especially important recently, due to ongoing debate in the field of protein evolution about how position-specific preferences for amino acids may change over time (Naumenko et al. 2012;Pollock et al. 2012;Ashenberg et al. 2013;Pollock and Goldstein 2014;Bazykin 2015;Doud et al. 2015;Goldstein et al. 2015;Risso et al. 2015;Shah et al. 2015;Usmanova et al. 2015). Specifically, several groups have suggested that once an amino acid substitution occurs at a particular position, epistatic interactions with subsequent substitutions at other positions should tend to increase the selective preference for the derived amino acid relative to the ancestral stat...

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Topological features of rugged fitness landscapes in sequence space

Cited by 101 publications

References 100 publications

Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms

Evolutionary consequences of drug resistance: shared principles across diverse targets and organisms

Changing preferences: deformation of single position amino acid fitness landscapes and evolution of proteins

Epistasis and the Dynamics of Reversion in Molecular Evolution

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