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Biological evolution can be conceptualized as a search process in the space of gene sequences guided by the fitness landscape, a mapping that assigns a measure of reproductive value to each genotype. Here we discuss probabilistic models of fitness landscapes with a focus on their evolutionary accessibility, where a path in a fitness landscape is said to be accessible if the fitness values encountered along the path increase monotonically. For uncorrelated (random) landscapes with independent and identically distributed fitness values, the probability of existence of accessible paths between genotypes at a distance linear in the sequence length $L$ becomes nonzero at a nontrivial threshold value of the fitness difference between the initial and final genotype, which can be explicitly computed for large classes of genotype graphs. The behaviour in uncorrelated random landscapes is contrasted with landscape models that display additional, biologically motivated structural features. In particular, landscapes defined by a tradeoff between adaptation to environmental extremes have been found to display a combinatorially large number of accessible paths to all local fitness maxima. We show that this property is characteristic of a broad class of models that satisfy a certain global constraint, and provide further examples from this class., Comment: Accepted contribution to the STATPHYS 28 issue of JSTAT; 30 pages, 10 figures

The translation of messenger RNA transcripts to proteins is commonly modeled as a one-dimensional totally asymmetric exclusion process with extended particles. Here we focus on the effects of premature termination of translation through the irreversible detachment of ribosomes. We consider a model where the detachment is induced by the unsuccessful attempt to move to an occupied site. The model is exactly solvable in a simplified geometry consisting of the translation initiation region followed by a single slow site representing a translation bottleneck. In agreement with recent experimental and computational studies we find a non-monotonic dependence of the ribosome current on the initiation rate, but only if the leading particle in a colliding pair detaches. Simulations show that the effect persists for larger lattices and extended bottlenecks. In the homogeneous system the ribosome density decays asymptotically as the inverse square root of the distance to the initiation site., Comment: 15 pages, 8 figures

We investigate two stochastic models of a growing population subject to selection and mutation. In our models each individual carries a fitness which determines its mean offspring number. Many of these offspring inherit their parent's fitness, but some are mutants and obtain a fitness randomly sampled from a distribution in the domain of attraction of the Fr\'echet distribution. We give a rigorous proof for the precise rate of superexponential growth of these stochastic processes and support the argument by a heuristic and numerical study of the mechanism underlying this growth., Comment: 29 pages, 3 figures

The extent of parallel evolution at the genotypic level is quantitatively linked to the distribution of beneficial fitness effects (DBFE) of mutations. The standard view, based on light-tailed distributions (i.e. distributions with finite moments), is that the probability of parallel evolution in duplicate populations is inversely proportional to the number of available mutations, and moreover that the DBFE is sufficient to determine the probability when the number of available mutations is large. Here we show that when the DBFE is heavy-tailed, as found in several recent experiments, these expectations are defied. The probability of parallel evolution decays anomalously slowly in the number of mutations or even becomes independent of it, implying higher repeatability of evolution. At the same time, the probability of parallel evolution is non-self-averaging, that is, it does not converge to its mean value even when a large number of mutations are involved. This behavior arises because the evolutionary process is dominated by only a few mutations of high weight. Consequently, the probability varies widely across systems with the same DBFE. Contrary to the standard view, the DBFE is no longer sufficient to determine the extent of parallel evolution, making it much less predictable. We illustrate these ideas theoretically and through analysis of empirical data on antibiotic resistance evolution.

A significant proportion of the infections driving the current {SARS-CoV-2} pandemic are transmitted asymptomatically. Here we introduce and study a simple epidemic model with separate compartments comprising asymptomatic and symptomatic infected individuals. The linear dynamics determining the outbreak condition of the model is equivalent to a renewal theory approach with exponential waiting time distributions. Exploiting a nontrivial conservation law of the full nonlinear dynamics, we derive analytic bounds on the peak number of infections in the absence and presence of mitigation through isolation and testing. The bounds are compared to numerical solutions of the differential equations., Comment: 15 pages, 4 figures

Biological evolution of a population is governed by the fitness landscape, which is a map from genotype to fitness. However, a fitness landscape depends on the organisms environment, and evolution in changing environments is still poorly understood. We study a particular model of antibiotic resistance evolution in bacteria where the antibiotic concentration is an environmental parameter and the fitness landscapes incorporate tradeoffs between adaptation to low and high antibiotic concentration. With evolutionary dynamics that follow fitness gradients, the evolution of the system under slowly changing antibiotic concentration resembles the athermal dynamics of disordered physical systems under external drives. Exploiting this resemblance, we show that our model can be described as a system with interacting hysteretic elements. As in the case of the driven disordered systems, adaptive evolution under antibiotic concentration cycling is found to exhibit hysteresis loops and memory formation. We derive a number of analytical results for quasistatic concentration changes. We also perform numerical simulations to study how these effects are modified under driving protocols in which the concentration is changed in discrete steps. Our approach provides a general framework for studying motifs of evolutionary dynamics in biological systems in a changing environment.

Darwinian evolution is driven by random mutations, genetic recombination (gene shuffling) and selection that favors genotypes with high fitness. For systems where each genotype can be represented as a bitstring of length $L$, an overview of possible evolutionary trajectories is provided by the $L$-cube graph with nodes labeled by genotypes and edges directed toward the genotype with higher fitness. Peaks (sinks in the graphs) are important since a population can get stranded at a suboptimal peak. The fitness landscape is defined by the fitness values of all genotypes in the system. Some notion of curvature is necessary for a more complete analysis of the landscapes, including the effect of recombination. The shape approach uses triangulations (shapes) induced by fitness landscapes. The main topic for this work is the interplay between peak patterns and shapes. Because of constraints on the shapes for $L=3$ imposed by peaks, there are in total 25 possible combinations of peak patterns and shapes. Similar constraints exist for higher $L$. Specifically, we show that the constraints induced by the staircase triangulation can be formulated as a condition of {\emph{universal positive epistasis}}, an order relation on the fitness effects of arbitrary sets of mutations that respects the inclusion relation between the corresponding genetic backgrounds. We apply the concept to a large protein fitness landscape for an immunoglobulin-binding protein expressed in Streptococcal bacteria., Comment: 25 pages, 6 figures

Understanding non-equilibrium phenomena, such as growth, and connecting them to equilibrium phase behavior is a major challenge, in particular for complex multicomponent materials. We use X-ray reflectivity to determine the surface roughness of binary mixtures of several prototypical organic compounds. By analyzing the roughness as a function of composition, we find a systematic behavior depending on the bulk phase behavior in terms of intermixing, co-crystallization or phase separation. Supported by kinetic Monte Carlo simulations, we provide evidence that the growth behavior can be rationalized by a lowered step edge barrier in the mixed films which is induced by reduced in-plane crystallinity., Comment: 10 pages, 9 figures

Motivated by recent experiments on an antibiotic resistance gene, we investigate genetic interactions between synonymous mutations in the framework of exclusion models of translation. We show that the range of possible interactions is markedly different depending on whether translation efficiency is assumed to be proportional to ribosome current or ribosome speed. In the first case every mutational effect has a definite sign that is independent of genetic background, whereas in the second case the effect-sign can vary depending on the presence of other mutations. The latter result is demonstrated using configurations of multiple translational bottlenecks induced by slow codons., Comment: 10 pages, 4 figures

Fisher's geometric model describes biological fitness landscapes by combining a linear map from the discrete space of genotypes to an $n$-dimensional Euclidean phenotype space with a nonlinear, single-peaked phenotype-fitness map. Genotypes are represented by binary sequences of length $L$, and the phenotypic effects of mutations at different sites are represented by $L$ random vectors drawn from an isotropic Gaussian distribution. Recent work has shown that the interplay between the genotypic and phenotypic levels gives rise to a range of different landscape topographies that can be characterised by the number of local fitness maxima. Extending our previous study of the mean number of local maxima, here we focus on the distribution of the number of maxima when the limit $L \to \infty$ is taken at finite $n$. We identify the typical scale of the number of maxima for general $n$, and determine the full scaled probability density and two point correlation function of maxima for the one-dimensional case. We also elaborate on the close relation of the model to the anti-ferromagnetic Hopfield model with $n$ random continuous pattern vectors, and show that many of our results carry over to this setting. More generally, we expect that our analysis can help to elucidate the fluctuation structure of metastable states in various spin glass problems., Comment: 36 pages, 5 figures. Minor corrections

Understanding how genotypes map onto phenotypes, fitness, and eventually organisms is arguably the next major missing piece in a fully predictive theory of evolution. We refer to this generally as the problem of the genotype-phenotype map. Though we are still far from achieving a complete picture of these relationships, our current understanding of simpler questions, such as the structure induced in the space of genotypes by sequences mapped to molecular structures, has revealed important facts that deeply affect the dynamical description of evolutionary processes. Empirical evidence supporting the fundamental relevance of features such as phenotypic bias is mounting as well, while the synthesis of conceptual and experimental progress leads to questioning current assumptions on the nature of evolutionary dynamics-cancer progression models or synthetic biology approaches being notable examples. This work delves into a critical and constructive attitude in our current knowledge of how genotypes map onto molecular phenotypes and organismal functions, and discusses theoretical and empirical avenues to broaden and improve this comprehension. As a final goal, this community should aim at deriving an updated picture of evolutionary processes soundly relying on the structural properties of genotype spaces, as revealed by modern techniques of molecular and functional analysis., Comment: 111 pages, 11 figures uses elsarticle latex class

A fitness landscape is a mapping from a space of discrete genotypes to the real numbers. A path in a fitness landscape is a sequence of genotypes connected by single mutational steps. Such a path is said to be accessible if the fitness values of the genotypes encountered along the path increase monotonically. We study accessible paths on random fitness landscapes of the House-of-Cards type, on which fitness values are independent, identically and continuously distributed random variables. The genotype space is taken to be a Cartesian power graph $\mathcal{A}^L$, where $L$ is the number of genetic loci and the allele graph $\mathcal{A}$ encodes the possible allelic states and mutational transitions on one locus. The probability of existence of accessible paths between two genotypes at a distance linear in $L$ displays a transition from 0 to a positive value at a threshold $\beta_c$ for the fitness difference between the initial and final genotype. We derive a lower bound on $\beta_c$ for general $\mathcal{A}$ and show that this bound is tight for a large class of allele graphs. Our results generalize previous results for accessibility percolation on the biallelic hypercube, and compare favorably to published numerical results for multiallelic Hamming graphs., Comment: 43 pages, 9 figures, 2 tables

The fitness landscape encodes the mapping of genotypes to fitness and provides a succinct representation of possible trajectories followed by an evolving population. Evolutionary accessibility is quantified by the existence of fitness-monotonic paths connecting far away genotypes. Studies of accessibility percolation use probabilistic fitness landscape models to explore the emergence of such paths as a function of the initial fitness, the parameters of the landscape or the structure of the genotype graph. This chapter reviews these studies and discusses their implications for the predictability of evolutionary processes., Comment: 20 pages, 3 figures

Mutational robustness quantifies the effect of random mutations on fitness. When mutational robustness is high, most mutations do not change fitness or have only a minor effect on it. From the point of view of fitness landscapes, robust genotypes form neutral networks of almost equal fitness. Using deterministic population models it has been shown that selection favors genotypes inside such networks, which results in increased mutational robustness. Here we demonstrate that this effect is massively enhanced by recombination. Our results are based on a detailed analysis of mesa-shaped fitness landscapes, where we derive precise expressions for the dependence of the robustness on the landscape parameters for recombining and non-recombining populations. In addition, we carry out numerical simulations on different types of random holey landscapes as well as on an empirical fitness landscape. We show that the mutational robustness of a genotype generally correlates with its recombination weight, a new measure that quantifies the likelihood for the genotype to arise from recombination. We argue that the favorable effect of recombination on mutational robustness is a highly universal feature that may have played an important role in the emergence and maintenance of mechanisms of genetic exchange., Comment: 15 figures, Supplementary appendix, supplementary figures

We report on the universality of height fluctuations at the crossing point of two interacting (1+1)-dimensional Kardar-Parisi-Zhang (KPZ) interfaces with curved and flat initial conditions. We introduce a control parameter p as the probability for the initially flat geometry to be chosen and compute the phase diagram as a function of p. We find that the distribution of the fluctuations converges to the Gaussian orthogonal ensemble Tracy-Widom (TW) distribution for p<0.5, and to the Gaussian unitary ensemble TW distribution for p>0.5. For p=0.5 where the two geometries are equally weighted, the behavior is governed by an emergent Gaussian statistics in the universality class of Brownian motion. We propose a phenomenological theory to explain our findings and discuss possible applications in nonequilibrium transport and traffic flow., Comment: 5 pages, 6 figures, Phys. Rev. Lett. (2019) (accepted)

Daily precipitation time series are composed of null entries corresponding to dry days and nonzero entries that describe the rainfall amounts on wet days. Assuming that wet days follow a Bernoulli process with success probability $p$, we show that the presence of dry days induces negative correlations between record-breaking precipitation events. The resulting non-monotonic behavior of the Fano factor of the record counting process is recovered in empirical data. We derive the full probability distribution $P(R,n)$ of the number of records $R_n$ up to time $n$, and show that for large $n$, its large deviation form coincides with that of a Poisson distribution with parameter $\ln(p\,n)$. We also study in detail the joint limit $p \to 0$, $n \to \infty$, which yields a random record model in continuous time $t = pn$., Comment: 11 pages, 2 figures + 13 pages and 2 figures of supplemental material

Muller's ratchet describes the irreversible accumulation of deleterious mutations in asexual populations. In well-mixed populations the speed of fitness decline is exponentially small in the population size, and any positive rate of beneficial mutations is sufficient to reverse the ratchet in large populations. The behavior is fundamentally different in populations with spatial structure, because the speed of the ratchet remains nonzero in the infinite size limit when the deleterious mutation rate exceeds a critical value. Based on the relation between the spatial ratchet and directed percolation, we develop a scaling theory incorporating both deleterious and beneficial mutations. The theory is verified by extensive simulations in one and two dimensions., Comment: 7 pages, 6 figures

These lecture notes introduce key concepts of mathematical population genetics within the most elementary setting and describe a few recent applications to microbial evolution experiments. Pointers to the literature for further reading are provided, and some of the derivations are left as exercises for the reader., Comment: 18 pages, 7 figures

The spreading of density fluctuations in two-dimensional driven diffusive systems is marginally anomalous. Mode coupling theory predicts that the diffusivity in the direction of the drive diverges with time as $(\ln t)^{2/3}$ with a prefactor depending on the macroscopic current-density relation and the diffusion tensor of the fluctuating hydrodynamic field equation. Here we present the first numerical verification of this behavior for a particular version of the two-dimensional asymmetric exclusion process. Particles jump strictly asymmetrically along one of the lattice directions and symmetrically along the other, and an anisotropy parameter $p$ governs the ratio between the two rates. Using a novel massively parallel coupling algorithm that strongly reduces the fluctuations in the numerical estimate of the two-point correlation function, we are able to accurately determine the exponent of the logarithmic correction. In addition, the variation of the prefactor with $p$ provides a stringent test of mode coupling theory., Comment: 14 pages, 4 figures

Kauffman's NK-model is a paradigmatic example of a class of stochastic models of genotypic fitness landscapes that aim to capture generic features of epistatic interactions in multilocus systems. Genotypes are represented as sequences of $L$ binary loci. The fitness assigned to a genotype is a sum of contributions, each of which is a random function defined on a subset of $k \le L$ loci. These subsets or neighborhoods determine the genetic interactions of the model. Whereas earlier work on the NK model suggested that most of its properties are robust with regard to the choice of neighborhoods, recent work has revealed an important and sometimes counter-intuitive influence of the interaction structure on the properties of NK fitness landscapes. Here we review these developments and present new results concerning the number of local fitness maxima and the statistics of selectively accessible (that is, fitness-monotonic) mutational pathways. In particular, we develop a unified framework for computing the exponential growth rate of the expected number of local fitness maxima as a function of $L$, and identify two different universality classes of interaction structures that display different asymptotics of this quantity for large $k$. Moreover, we show that the probability that the fitness landscape can be traversed along an accessible path decreases exponentially in $L$ for a large class of interaction structures that we characterize as locally bounded. Finally, we discuss the impact of the NK interaction structures on the dynamics of evolution using adaptive walk models., Comment: 61 pages, 9 figures

Whether evolution can be predicted is a key question in evolutionary biology. Here we set out to better understand the repeatability of evolution. We explored experimentally the effect of mutation supply and the strength of selective pressure on the repeatability of selection from standing genetic variation. Different sizes of mutant libraries of an antibiotic resistance gene, TEM-1 $\beta$-lactamase in Escherichia coli, were subjected to different antibiotic concentrations. We determined whether populations went extinct or survived, and sequenced the TEM gene of the surviving populations. The distribution of mutations per allele in our mutant libraries- generated by error-prone PCR- followed a Poisson distribution. Extinction patterns could be explained by a simple stochastic model that assumed the sampling of beneficial mutations was key for survival. In most surviving populations, alleles containing at least one known large-effect beneficial mutation were present. These genotype data also support a model which only invokes sampling effects to describe the occurrence of alleles containing large-effect driver mutations. Hence, evolution is largely predictable given cursory knowledge of mutational fitness effects, the mutation rate and population size. There were no clear trends in the repeatability of selected mutants when we considered all mutations present. However, when only known large-effect mutations were considered, the outcome of selection is less repeatable for large libraries, in contrast to expectations. Furthermore, we show experimentally that alleles carrying multiple mutations selected from large libraries confer higher resistance levels relative to alleles with only a known large-effect mutation, suggesting that the scarcity of high-resistance alleles carrying multiple mutations may contribute to the decrease in repeatability at large library sizes., Comment: 31pages, 9 figures

Fisher's geometric model was originally introduced to argue that complex adaptations must occur in small steps because of pleiotropic constraints. When supplemented with the assumption of additivity of mutational effects on phenotypic traits, it provides a simple mechanism for the emergence of genotypic epistasis from the nonlinear mapping of phenotypes to fitness. Of particular interest is the occurrence of reciprocal sign epistasis, which is a necessary condition for multipeaked genotypic fitness landscapes. Here we compute the probability that a pair of randomly chosen mutations interacts sign epistatically, which is found to decrease with increasing phenotypic dimension $n$, and varies nonmonotonically with the distance from the phenotypic optimum. We then derive expressions for the mean number of fitness maxima in genotypic landscapes comprised of all combinations of $L$ random mutations. This number increases exponentially with $L$, and the corresponding growth rate is used as a measure of the complexity of the landscape. The dependence of the complexity on the model parameters is found to be surprisingly rich, and three distinct phases characterized by different landscape structures are identified. Our analysis shows that the phenotypic dimension, which is often referred to as phenotypic complexity, does not generally correlate with the complexity of fitness landscapes and that even organisms with a single phenotypic trait can have complex landscapes. Our results further inform the interpretation of experiments where the parameters of Fisher's model have been inferred from data, and help to elucidate which features of empirical fitness landscapes can be described by this model., Comment: 27 pages, 14 figures, 2 tables, minor changes (published version)

We study the importance of local structural properties in networks which have been evolved for a power-law scaling in their Laplacian spectrum. To this end, the degree distribution, two-point degree correlations, and degree-dependent clustering are extracted from the evolved networks and used to construct random networks with the prescribed distributions. In the analysis of these reconstructed networks it turns out that the degree distribution alone is not sufficient to generate the spectral scaling and the degree-dependent clustering has only an indirect influence. The two-point correlations are found to be the dominant characteristic for the power-law scaling over a broader eigenvalue range., Comment: 9 pages, 8 figures

We study a modified record process where the $k$'th record in a series of independent and identically distributed random variables is defined recursively through the condition $Y_k > Y_{k-1} - \delta_{k-1}$ with a deterministic sequence $\delta_k > 0$ called the handicap. For constant $\delta_k \equiv \delta$ and exponentially distributed random variables it has been shown in previous work that the process displays a phase transition as a function of $\delta$ between a normal phase where the mean record value increases indefinitely and a stationary phase where the mean record value remains bounded and a finite fraction of all entries are records (Park \textit{et al} 2015 {\it Phys. Rev.} E \textbf{91} 042707). Here we explore the behavior for general probability distributions and decreasing and increasing sequences $\delta_k$, focusing in particular on the case when $\delta_k$ matches the typical spacing between subsequent records in the underlying simple record process without handicap. We find that a continuous phase transition occurs only in the exponential case, but a novel kind of first order transition emerges when $\delta_k$ is increasing. The problem is partly motivated by the dynamics of evolutionary adaptation in biological fitness landscapes, where $\delta_k$ corresponds to the change of the deterministic fitness component after $k$ mutational steps. The results for the record process are used to compute the mean number of steps that a population performs in such a landscape before being trapped at a local fitness maximum., Comment: minor changes. Published

We study adaptation of a haploid asexual population on a fitness landscape defined over binary genotype sequences of length $L$. We consider greedy adaptive walks in which the population moves to the fittest among all single mutant neighbors of the current genotype until a local fitness maximum is reached. The landscape is of the rough mount Fuji type, which means that the fitness value assigned to a sequence is the sum of a random and a deterministic component. The random components are independent and identically distributed random variables, and the deterministic component varies linearly with the distance to a reference sequence. The deterministic fitness gradient $c$ is a parameter that interpolates between the limits of an uncorrelated random landscape ($c = 0$) and an effectively additive landscape ($c \to \infty$). When the random fitness component is chosen from the Gumbel distribution, explicit expressions for the distribution of the number of steps taken by the greedy walk are obtained, and it is shown that the walk length varies non-monotonically with the strength of the fitness gradient when the starting point is sufficiently close to the reference sequence. Asymptotic results for general distributions of the random fitness component are obtained using extreme value theory, and it is found that the walk length attains a non-trivial limit for $L \to \infty$, different from its values for $c=0$ and $c = \infty$, if $c$ is scaled with $L$ in an appropriate combination., Comment: minor changes

Fitness landscapes are genotype to fitness mappings commonly used in evolutionary biology and computer science which are closely related to spin glass models. In this paper, we study the NK model for fitness landscapes where the interaction scheme between genes can be explicitly defined. The focus is on how this scheme influences the overall shape of the landscape. Our main tool for the analysis are adaptive walks, an idealized dynamics by which the population moves uphill in fitness and terminates at a local fitness maximum. We use three different types of walks and investigate how their length (the number of steps required to reach a local peak) and height (the fitness at the endpoint of the walk) depend on the dimensionality and structure of the landscape. We find that the distribution of local maxima over the landscape is particularly sensitive to the choice of interaction pattern. Most quantities that we measure are simply correlated to the rank of the scheme, which is equal to the number of nonzero coefficients in the expansion of the fitness landscape in terms of Walsh functions., Comment: 29 pages, 9 figures

Networks with a prescribed power-law scaling in the spectrum of the graph Laplacian can be generated by evolutionary optimization. The Laplacian spectrum encodes the dynamical behavior of many important processes. Here, the networks are evolved to exhibit subdiffusive dynamics. Under the additional constraint of degree-regularity, the evolved networks display an abundance of symmetric motifs arranged into loops and long linear segments. Exploiting results from algebraic graph theory on symmetric networks, we find the underlying backbone structures and how they contribute to the spectrum. The resulting coarse-grained networks provide an intuitive view of how the anomalous diffusive properties can be realized in the evolved structures., Comment: 6 pages, 5 figures

We study biological evolution on a random fitness landscape where correlations are introduced through a linear fitness gradient of strength $c$. When selection is strong and mutations rare the dynamics is a directed uphill walk that terminates at a local fitness maximum. We analytically calculate the dependence of the walk length on the genome size $L$. When the distribution of the random fitness component has an exponential tail we find a phase transition of the walk length $D$ between a phase at small $c$ where walks are short $(D \sim \ln L)$ and a phase at large $c$ where walks are long $(D \sim L)$. For all other distributions only a single phase exists for any $c > 0$. The considered process is equivalent to a zero temperature Metropolis dynamics for the random energy model in an external magnetic field, thus also providing insight into the aging dynamics of spin glasses.

Identifying and quantifying the benefits of sex and recombination is a long standing problem in evolutionary theory. In particular, contradictory claims have been made about the existence of a benefit of recombination on high dimensional fitness landscapes in the presence of sign epistasis. Here we present a comparative numerical study of sexual and asexual evolutionary dynamics of haploids on tunably rugged model landscapes under strong selection, paying special attention to the temporal development of the evolutionary advantage of recombination and the link between population diversity and the rate of adaptation. We show that the adaptive advantage of recombination on static rugged landscapes is strictly transitory. At early times, an advantage of recombination arises through the possibility to combine individually occurring beneficial mutations, but this effect is reversed at longer times by the much more efficient trapping of recombining populations at local fitness peaks. These findings are explained by means of well established results for a setup with only two loci. In accordance with the Red Queen hypothesis the transitory advantage can be prolonged indefinitely in fluctuating environments, and it is maximal when the environment fluctuates on the same time scale on which trapping at local optima typically occurs., Comment: 34 pages, 9 figures and 8 supplementary figures; revised and final version

Much of the current theory of adaptation is based on Gillespie's mutational landscape model (MLM), which assumes that the fitness values of genotypes linked by single mutational steps are independent random variables. On the other hand, a growing body of empirical evidence shows that real fitness landscapes, while possessing a considerable amount of ruggedness, are smoother than predicted by the MLM. In the present article we propose and analyse a simple fitness landscape model with tunable ruggedness based on the Rough Mount Fuji (RMF) model originally introduced by Aita et al. [Biopolymers 54:64-79 (2000)] in the context of protein evolution. We provide a comprehensive collection of results pertaining to the topographical structure of RMF landscapes, including explicit formulae for the expected number of local fitness maxima, the location of the global peak, and the fitness correlation function. The statistics of single and multiple adaptive steps on the RMF landscape are explored mainly through simulations, and the results are compared to the known behavior in the MLM model. Finally, we show that the RMF model can explain the large number of second-step mutations observed on a highly-fit first step backgound in a recent evolution experiment with a microvirid bacteriophage [Miller et al., Genetics 187:185-202 (2011)]., Comment: 43 pages, 12 figures; revised version with new results on the number of fitness maxima

A fitness landscape is a mapping from the space of genetic sequences, which is modeled here as a binary hypercube of dimension $L$, to the real numbers. We consider random models of fitness landscapes, where fitness values are assigned according to some probabilistic rule, and study the statistical properties of pathways to the global fitness maximum along which fitness increases monotonically. Such paths are important for evolution because they are the only ones that are accessible to an adapting population when mutations occur at a low rate. The focus of this work is on the block model introduced by A.S. Perelson and C.A. Macken [Proc. Natl. Acad. Sci. USA 92:9657 (1995)] where the genome is decomposed into disjoint sets of loci (`modules') that contribute independently to fitness, and fitness values within blocks are assigned at random. We show that the number of accessible paths can be written as a product of the path numbers within the blocks, which provides a detailed analytic description of the path statistics. The block model can be viewed as a special case of Kauffman's NK-model, and we compare the analytic results to simulations of the NK-model with different genetic architectures. We find that the mean number of accessible paths in the different versions of the model are quite similar, but the distribution of the path number is qualitatively different in the block model due to its multiplicative structure. A similar statement applies to the number of local fitness maxima in the NK-models, which has been studied extensively in previous works. The overall evolutionary accessibility of the landscape, as quantified by the probability to find at least one accessible path to the global maximum, is dramatically lowered by the modular structure., Comment: 26 pages, 12 figures; final version with some typos corrected

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. 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 fitness effects. We solve the 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. 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., Comment: Title has been changed. Supporting Information (animation) can be found in the source file. 53 pages. 10 figures. To appear in Genetics

Competition between independently arising beneficial mutations is enhanced in spatial populations due to the linear rather than exponential growth of clones. Recent theoretical studies have pointed out that the resulting fitness dynamics is analogous to a surface growth process, where new layers nucleate and spread stochastically, leading to the build up of scale-invariant roughness. This scenario differs qualitatively from the standard view of adaptation in that the speed of adaptation becomes independent of population size while the fitness variance does not. Here we exploit recent progress in the understanding of surface growth processes to obtain precise predictions for the universal, non-Gaussian shape of the fitness distribution for one-dimensional habitats, which are verified by simulations. When the mutations are deleterious rather than beneficial the problem becomes a spatial version of Muller's ratchet. In contrast to the case of well-mixed populations, the rate of fitness decline remains finite even in the limit of an infinite habitat, provided the ratio $U_d/s^2$ between the deleterious mutation rate and the square of the (negative) selection coefficient is sufficiently large. Using again an analogy to surface growth models we show that the transition between the stationary and the moving state of the ratchet is governed by directed percolation.

Accessibility percolation is a new type of percolation problem inspired by evolutionary biology. To each vertex of a graph a random number is assigned and a path through the graph is called accessible if all numbers along the path are in ascending order. For the case when the random variables are independent and identically distributed, we derive an asymptotically exact expression for the probability that there is at least one accessible path from the root to the leaves in an $n$-tree. This probability tends to 1 (0) if the branching number is increased with the height of the tree faster (slower) than linearly. When the random variables are biased such that the mean value increases linearly with the distance from the root, a percolation threshold emerges at a finite value of the bias., Comment: 6 pages, 4 figures

Starting from fitness correlation functions, we calculate exact expressions for the amplitude spectra of fitness landscapes as defined by P.F. Stadler [J. Math. Chem. 20, 1 (1996)] for common landscape models, including Kauffman's NK-model, rough Mount Fuji landscapes and general linear superpositions of such landscapes. We further show that correlations decaying exponentially with the Hamming distance yield exponentially decaying spectra similar to those reported recently for a model of molecular signal transduction. Finally, we compare our results for the model systems to the spectra of various experimentally measured fitness landscapes. We claim that our analytical results should be helpful when trying to interpret empirical data and guide the search for improved fitness landscape models., Comment: 13 pages, 5 figures; revised and final version

We analyze the occurrence and the values of record-breaking temperatures in daily and monthly temperature observations. Our aim is to better understand and quantify the statistics of temperature records in the context of global warming. Similar to earlier work we employ a simple mathematical model of independent and identically distributed random variables with a linearly growing expectation value. This model proved to be useful in predicting the increase (decrease) in upper (lower) temperature records in a warming climate. Using both station and re-analysis data from Europe and the United States we further investigate the statistics of temperature records and the validity of this model. The most important new contribution in this article is an analysis of the statistics of record values for our simple model and European reanalysis data. We estimate how much the mean values and the distributions of record temperatures are affected by the large scale warming trend. In this context we consider both the values of records that occur at a certain time and the values of records that have a certain record number in the series of record events. We compare the observational data both to simple analytical computations and numerical simulations. We find that it is more difficult to describe the values of record breaking temperatures within the framework of our linear drift model. Observations from the summer months fit well into the model with Gaussian random variables under the observed linear warming, in the sense that record breaking temperatures are more extreme in the summer. In winter however a significant asymmetry of the daily temperature distribution hides the effect of the slow warming trends. Therefore very extreme cold records are still possible in winter. This effect is even more pronounced if one considers only data from subpolar regions., Comment: 16 pages, 20 figures, revised version, published in Climate Dynamics

This is an extended abstract of lectures delivered at the 4th Warsaw Summer School on Statistical Physics in Kazimierz Dolny, June 25-July 2, 2011.

The adaptive evolution of a population under the influence of mutation and selection is strongly influenced by the structure of the underlying fitness landscape, which encodes the interactions between mutations at different genetic loci. Theoretical studies of such landscapes have been carried out for several decades, but only recently experimental fitness measurements encompassing all possible combinations of small sets of mutations have become available. The empirical studies have spawned new questions about the accessibility of optimal genotypes under natural selection. Depending on population dynamic parameters such as mutation rate and population size, evolutionary accessibility can be quantified through the statistics of accessible mutational pathways (along which fitness increases monotoncially), or through the study of the basin of attraction of the optimal genotype under greedy (steepest ascent) dynamics. Here we investigate these two measures of accessibility in the framework of Kauffman's $LK$-model, a paradigmatic family of random fitness landscapes with tunable ruggedness. The key parameter governing the strength of genetic interactions is the number $K$ of interaction partners of each of the $L$ sites in the genotype sequence. In general, accessibility increases with increasing genotype dimensionality $L$ and decreases with increasing number of interactions $K$. Remarkably, however, we find that some measures of accessibility behave non-monotonically as a function of $K$, indicating a special role of the most sparsely connected, non-trivial cases K=1 and 2. The relation between models for fitness landscapes and spin glasses is also addressed., Comment: 22 pages, 13 Figures

The concept of a fitness landscape is a powerful metaphor that offers insight into various aspects of evolutionary processes and guidance for the study of evolution. Until recently, empirical evidence on the ruggedness of these landscapes was lacking, but since it became feasible to construct all possible genotypes containing combinations of a limited set of mutations, the number of studies has grown to a point where a classification of landscapes becomes possible. The aim of this review is to identify measures of epistasis that allow a meaningful comparison of fitness landscapes and then apply them to the empirical landscapes to discern factors that affect ruggedness. The various measures of epistasis that have been proposed in the literature appear to be equivalent. Our comparison shows that the ruggedness of the empirical landscape is affected by whether the included mutations are beneficial or deleterious and by whether intra- or intergenic epistasis is involved. Finally, the empirical landscapes are compared to landscapes generated with the Rough Mt.\ Fuji model. Despite the simplicity of this model, it captures the features of the experimental landscapes remarkably well., Comment: 24 pages, 5 figures; to appear in Journal of Statistical Mechanics: Theory and Experiment

We report new results on the non-conserved dynamics of parallel steps on vicinal surfaces in the case of sublimation with electromigration and step-step interactions. The derived equations are valid in the quasistatic approximation and in the limit $f^{-1}\gg l_D\gg l_{\pm} \gg l_i$, where $f$ is the inverse electromigration length, $l_D$ the diffusion length, $l_{\pm}$ the kinetic lengths and $l_i$ the terrace widths. The coupling between crystal sublimation and step-step interactions induces non-linear, non-conservative terms in the equations of motion. Depending on the initial conditions, this leads to interrupted coarsening, anticoarsening of step bunches or periodic switching between step trains of different numbers of bunches., Comment: 11 pages, 4 figures; revised and extended version