Quantitative analyses of empirical fitness landscapes

Szendro, Ivan G.; Schenk, Martijn; Franke, Jasper; Krug, Joachim; Visser, Jaap

doi:10.1088/1742-5468/2013/01/p01005

Cited by 251 publications

(408 citation statements)

References 88 publications

(172 reference statements)

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“…Each subgraph represented a classical adaptive landscape connecting WT to a beneficial quadruple mutant, analogous to previously studied protein fitness landscapes (Weinreich et al, 2006;Szendro et al, 2013). Each variant is denoted by the single letter code of amino acids across sites 39, 40, 41 and 54 (for example, WT sequence is VDGV).…”

Section: Direct Paths Of Adaptation Are Constrained By Pairwise Epistmentioning

confidence: 99%

“…We decomposed the fitness landscape into epistatic interactions of different orders by Fourier analysis (Stadler, 1996;Szendro et al, 2013;Weinreich et al, 2013;Neidhart et al, 2013). The Fourier coefficients given by the transform can be interpreted as epistasis of different orders (Weinreich et al, 2013;de Visser and Krug, 2014).…”

Section: Fourier Analysismentioning

confidence: 99%

“…Large-scale datasets combined with quantitative analysis have successfully unraveled important features of empirical fitness landscapes (Kouyos et al, 2012;Barton et al, 2015;Szendro et al, 2013). Nevertheless, there is a huge gap between the limited throughput of fitness measurements (usually on the order of 10 2 variants) and the vast size of sequence space.…”

Section: Introductionmentioning

confidence: 99%

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Adaptation in protein fitness landscapes is facilitated by indirect paths

Dai

Olson

et al. 2016

Preprint

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The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20 L ) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 20 4 = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve.

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Section: Direct Paths Of Adaptation Are Constrained By Pairwise Epistmentioning

confidence: 99%

Section: Fourier Analysismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Adaptation in protein fitness landscapes is facilitated by indirect paths

Dai

Olson

et al. 2016

Preprint

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“…Furthermore, recent experimental analyses of empirical fitness landscapes seem to indicate that a particularly strong form of epistasis termed sign epistasis (Weinreich et al 2005) is quite common (Weinreich et al 2006;de Visser et al 2009;Franke et al 2011;Szendro et al 2013b). Sign epistasis generally implies that the fitness landscape is rugged.…”

mentioning

confidence: 99%

Rate of Adaptation in Sexuals and Asexuals: A Solvable Model of the Fisher–Muller Effect

Park

Krug

2013

Genetics

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The adaptation of large asexual populations is hampered by the competition between independently arising beneficial mutations in different individuals, which is known as clonal interference. In classic work, Fisher and Muller proposed that recombination provides an evolutionary advantage in large populations by alleviating this competition. Based on recent progress in quantifying the speed of adaptation in asexual populations undergoing clonal interference, we present a detailed analysis of the Fisher-Muller mechanism for a model genome consisting of two loci with an infinite number of beneficial alleles each and multiplicative (nonepistatic) fitness effects. We solve the deterministic, infinite population dynamics exactly and show that, for a particular, natural mutation scheme, the speed of adaptation in sexuals is twice as large as in asexuals. This result is argued to hold for any nonzero value of the rate of recombination. Guided by the infinite population result and by previous work on asexual adaptation, we postulate an expression for the speed of adaptation in finite sexual populations that agrees with numerical simulations over a wide range of population sizes and recombination rates. The ratio of the sexual to asexual adaptation speed is a function of population size that increases in the clonal interference regime and approaches 2 for extremely large populations. The simulations also show that the imbalance between the numbers of accumulated mutations at the two loci is strongly suppressed even by a small amount of recombination. The generalization of the model to an arbitrary number L of loci is briefly discussed. If each offspring samples the alleles at each locus from the gene pool of the whole population rather than from two parents, the ratio of the sexual to asexual adaptation speed is approximately equal to L in large populations. A possible realization of this scenario is the reassortment of genetic material in RNA viruses with L genomic segments.T HE evolutionary advantage of sex remains one of the most intriguing puzzles in evolutionary biology (Kondrashov 1993;de Visser and Elena 2007;Otto 2009). Many hypotheses explaining why sexual reproduction is widespread in nature despite apparent disadvantages such as the twofold cost of sex have been suggested (Maynard Smith 1978). Well-known examples are the deterministic mutation hypothesis (Kondrashov 1988), the Fisher-Muller (FM) mechanism (Fisher 1930;Muller 1932;Crow and Kimura 1965), and Muller's ratchet (Muller 1964;Felsenstein 1974), to name only a few. These three hypotheses are applicable when the fitness landscape in question has certain specific features. Specifically, the deterministic mutation hypothesis requires deleterious mutations to be synergistically epistatic, while the Fisher-Muller mechanism as well as Muller's ratchet can explain the advantage of sex if epistasis is negligible.Theoretical analyses of the effect of epistasis on the speed of Muller's ratchet have concluded that it practically stops operating when epis...

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“…Indeed, the number of peaks in a landscape ultimately depends on whether mutations interact multiplicatively or epistatically in determining fitness [3]. Especially, if epistasis takes the form of sign [6] or reciprocal sign [7], landscapes are highly rugged and the number of accessible pathways will be limited [8][9][10].…”

Section: Introductionmentioning

confidence: 99%

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

2016

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Predicting viral evolution has proven to be a particularly difficult task, mainly owing to our incomplete knowledge of some of the fundamental principles that drive it. Recently, valuable information has been provided about mutation and recombination rates, the role of genetic drift and the distribution of mutational, epistatic and pleiotropic fitness effects. However, information about the topography of virus' adaptive landscapes is still scarce, and to our knowledge no data has been reported so far on how its ruggedness may condition virus' evolvability. Here, we show that populations of an RNA virus move efficiently on a rugged landscape and scape from the basin of attraction of a local optimum. We have evolved a set of Tobacco etch virus genotypes located at increasing distances from a local adaptive optimum in a highly rugged fitness landscape, and we observed that few evolved lineages remained trapped in the local optimum, while many others explored distant regions of the landscape. Most of the diversification in fitness among the evolved lineages was explained by adaptation, while historical contingency and chance events contribution was less important. Our results demonstrate that the ruggedness of adaptive landscapes is not an impediment for RNA viruses to efficiently explore remote parts of it.

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Quantitative analyses of empirical fitness landscapes

Cited by 251 publications

References 88 publications

Adaptation in protein fitness landscapes is facilitated by indirect paths

Adaptation in protein fitness landscapes is facilitated by indirect paths

Rate of Adaptation in Sexuals and Asexuals: A Solvable Model of the Fisher–Muller Effect

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

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