TY - JOUR AB - Dispersal is a crucial factor in natural evolution, since it determines the habitat experienced by any population and defines the spatial scale of interactions between individuals. There is compelling evidence for systematic differences in dispersal characteristics within the same population, i.e., genotype-dependent dispersal. The consequences of genotype-dependent dispersal on other evolutionary phenomena, however, are poorly understood. In this article we investigate the effect of genotype-dependent dispersal on spatial gene frequency patterns, using a generalization of the classical diffusion model of selection and dispersal. Dispersal is characterized by the variance of dispersal (diffusion coefficient) and the mean displacement (directional advection term). We demonstrate that genotype-dependent dispersal may change the qualitative behavior of Fisher waves, which change from being “pulled” to being “pushed” wave fronts as the discrepancy in dispersal between genotypes increases. The speed of any wave is partitioned into components due to selection, genotype-dependent variance of dispersal, and genotype-dependent mean displacement. We apply our findings to wave fronts maintained by selection against heterozygotes. Furthermore, we identify a benefit of increased variance of dispersal, quantify its effect on the speed of the wave, and discuss the implications for the evolution of dispersal strategies. AU - Novak, Sebastian AU - Kollár, Richard ID - 1169 IS - 1 JF - Genetics SN - 00166731 TI - Spatial gene frequency waves under genotype dependent dispersal VL - 205 ER - TY - JOUR AB - Adaptation depends critically on the effects of new mutations and their dependency on the genetic background in which they occur. These two factors can be summarized by the fitness landscape. However, it would require testing all mutations in all backgrounds, making the definition and analysis of fitness landscapes mostly inaccessible. Instead of postulating a particular fitness landscape, we address this problem by considering general classes of landscapes and calculating an upper limit for the time it takes for a population to reach a fitness peak, circumventing the need to have full knowledge about the fitness landscape. We analyze populations in the weak-mutation regime and characterize the conditions that enable them to quickly reach the fitness peak as a function of the number of sites under selection. We show that for additive landscapes there is a critical selection strength enabling populations to reach high-fitness genotypes, regardless of the distribution of effects. This threshold scales with the number of sites under selection, effectively setting a limit to adaptation, and results from the inevitable increase in deleterious mutational pressure as the population adapts in a space of discrete genotypes. Furthermore, we show that for the class of all unimodal landscapes this condition is sufficient but not necessary for rapid adaptation, as in some highly epistatic landscapes the critical strength does not depend on the number of sites under selection; effectively removing this barrier to adaptation. AU - Heredia, Jorge AU - Trubenova, Barbora AU - Sudholt, Dirk AU - Paixao, Tiago ID - 1111 IS - 2 JF - Genetics SN - 00166731 TI - Selection limits to adaptive walks on correlated landscapes VL - 205 ER - TY - JOUR AB - Viral capsids are structurally constrained by interactions among the amino acids (AAs) of their constituent proteins. Therefore, epistasis is expected to evolve among physically interacting sites and to influence the rates of substitution. To study the evolution of epistasis, we focused on the major structural protein of the fX174 phage family by first reconstructing the ancestral protein sequences of 18 species using a Bayesian statistical framework. The inferred ancestral reconstruction differed at eight AAs, for a total of 256 possible ancestral haplotypes. For each ancestral haplotype and the extant species, we estimated, in silico, the distribution of free energies and epistasis of the capsid structure. We found that free energy has not significantly increased but epistasis has. We decomposed epistasis up to fifth order and found that higher-order epistasis sometimes compensates pairwise interactions making the free energy seem additive. The dN/dS ratio is low, suggesting strong purifying selection, and that structure is under stabilizing selection. We synthesized phages carrying ancestral haplotypes of the coat protein gene and measured their fitness experimentally. Our findings indicate that stabilizing mutations can have higher fitness, and that fitness optima do not necessarily coincide with energy minima. AU - Fernandes Redondo, Rodrigo A AU - Vladar, Harold AU - Włodarski, Tomasz AU - Bollback, Jonathan P ID - 1077 IS - 126 JF - Journal of the Royal Society Interface SN - 17425689 TI - Evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family VL - 14 ER - TY - JOUR AB - Recently it has become feasible to detect long blocks of nearly identical sequence shared between pairs of genomes. These IBD blocks are direct traces of recent coalescence events and, as such, contain ample signal to infer recent demography. Here, we examine sharing of such blocks in two-dimensional populations with local migration. Using a diffusion approximation to trace genetic ancestry, we derive analytical formulae for patterns of isolation by distance of IBD blocks, which can also incorporate recent population density changes. We introduce an inference scheme that uses a composite likelihood approach to fit these formulae. We then extensively evaluate our theory and inference method on a range of scenarios using simulated data. We first validate the diffusion approximation by showing that the theoretical results closely match the simulated block sharing patterns. We then demonstrate that our inference scheme can accurately and robustly infer dispersal rate and effective density, as well as bounds on recent dynamics of population density. To demonstrate an application, we use our estimation scheme to explore the fit of a diffusion model to Eastern European samples in the POPRES data set. We show that ancestry diffusing with a rate of σ ≈ 50–100 km/√gen during the last centuries, combined with accelerating population growth, can explain the observed exponential decay of block sharing with increasing pairwise sample distance. AU - Ringbauer, Harald AU - Coop, Graham AU - Barton, Nicholas H ID - 1074 IS - 3 JF - Genetics SN - 00166731 TI - Inferring recent demography from isolation by distance of long shared sequence blocks VL - 205 ER - TY - JOUR AB - Severe environmental change can drive a population extinct unless the population adapts in time to the new conditions (“evolutionary rescue”). How does biparental sexual reproduction influence the chances of population persistence compared to clonal reproduction or selfing? In this article, we set up a one‐locus two‐allele model for adaptation in diploid species, where rescue is contingent on the establishment of the mutant homozygote. Reproduction can occur by random mating, selfing, or clonally. Random mating generates and destroys the rescue mutant; selfing is efficient at generating it but at the same time depletes the heterozygote, which can lead to a low mutant frequency in the standing genetic variation. Due to these (and other) antagonistic effects, we find a nontrivial dependence of population survival on the rate of sex/selfing, which is strongly influenced by the dominance coefficient of the mutation before and after the environmental change. Importantly, since mating with the wild‐type breaks the mutant homozygote up, a slow decay of the wild‐type population size can impede rescue in randomly mating populations. AU - Uecker, Hildegard ID - 1063 IS - 4 JF - Evolution SN - 00143820 TI - Evolutionary rescue in randomly mating, selfing, and clonal populations VL - 71 ER - TY - JOUR AB - Assortative mating is an important driver of speciation in populations with gene flow and is predicted to evolve under certain conditions in few-locus models. However, the evolution of assortment is less understood for mating based on quantitative traits, which are often characterized by high genetic variability and extensive linkage disequilibrium between trait loci. We explore this scenario for a two-deme model with migration, by considering a single polygenic trait subject to divergent viability selection across demes, as well as assortative mating and sexual selection within demes, and investigate how trait divergence is shaped by various evolutionary forces. Our analysis reveals the existence of sharp thresholds of assortment strength, at which divergence increases dramatically. We also study the evolution of assortment via invasion of modifiers of mate discrimination and show that the ES assortment strength has an intermediate value under a range of migration-selection parameters, even in diverged populations, due to subtle effects which depend sensitively on the extent of phenotypic variation within these populations. The evolutionary dynamics of the polygenic trait is studied using the hypergeometric and infinitesimal models. We further investigate the sensitivity of our results to the assumptions of the hypergeometric model, using individual-based simulations. AU - Sachdeva, Himani AU - Barton, Nicholas H ID - 990 IS - 6 JF - Evolution; International Journal of Organic Evolution SN - 00143820 TI - Divergence and evolution of assortative mating in a polygenic trait model of speciation with gene flow VL - 71 ER - TY - JOUR AB - Understanding the relation between genotype and phenotype remains a major challenge. The difficulty of predicting individual mutation effects, and particularly the interactions between them, has prevented the development of a comprehensive theory that links genotypic changes to their phenotypic effects. We show that a general thermodynamic framework for gene regulation, based on a biophysical understanding of protein-DNA binding, accurately predicts the sign of epistasis in a canonical cis-regulatory element consisting of overlapping RNA polymerase and repressor binding sites. Sign and magnitude of individual mutation effects are sufficient to predict the sign of epistasis and its environmental dependence. Thus, the thermodynamic model offers the correct null prediction for epistasis between mutations across DNA-binding sites. Our results indicate that a predictive theory for the effects of cis-regulatory mutations is possible from first principles, as long as the essential molecular mechanisms and the constraints these impose on a biological system are accounted for. AU - Lagator, Mato AU - Paixao, Tiago AU - Barton, Nicholas H AU - Bollback, Jonathan P AU - Guet, Calin C ID - 954 JF - eLife SN - 2050084X TI - On the mechanistic nature of epistasis in a canonical cis-regulatory element VL - 6 ER - TY - JOUR AB - Gene expression is controlled by networks of regulatory proteins that interact specifically with external signals and DNA regulatory sequences. These interactions force the network components to co-evolve so as to continually maintain function. Yet, existing models of evolution mostly focus on isolated genetic elements. In contrast, we study the essential process by which regulatory networks grow: the duplication and subsequent specialization of network components. We synthesize a biophysical model of molecular interactions with the evolutionary framework to find the conditions and pathways by which new regulatory functions emerge. We show that specialization of new network components is usually slow, but can be drastically accelerated in the presence of regulatory crosstalk and mutations that promote promiscuous interactions between network components. AU - Friedlander, Tamar AU - Prizak, Roshan AU - Barton, Nicholas H AU - Tkacik, Gasper ID - 955 IS - 1 JF - Nature Communications SN - 20411723 TI - Evolution of new regulatory functions on biophysically realistic fitness landscapes VL - 8 ER - TY - JOUR AB - The role of natural selection in the evolution of adaptive phenotypes has undergone constant probing by evolutionary biologists, employing both theoretical and empirical approaches. As Darwin noted, natural selection can act together with other processes, including random changes in the frequencies of phenotypic differences that are not under strong selection, and changes in the environment, which may reflect evolutionary changes in the organisms themselves. As understanding of genetics developed after 1900, the new genetic discoveries were incorporated into evolutionary biology. The resulting general principles were summarized by Julian Huxley in his 1942 book Evolution: the modern synthesis. Here, we examine how recent advances in genetics, developmental biology and molecular biology, including epigenetics, relate to today's understanding of the evolution of adaptations. We illustrate how careful genetic studies have repeatedly shown that apparently puzzling results in a wide diversity of organisms involve processes that are consistent with neo-Darwinism. They do not support important roles in adaptation for processes such as directed mutation or the inheritance of acquired characters, and therefore no radical revision of our understanding of the mechanism of adaptive evolution is needed. AU - Charlesworth, Deborah AU - Barton, Nicholas H AU - Charlesworth, Brian ID - 953 IS - 1855 JF - Proceedings of the Royal Society of London Series B Biological Sciences TI - The sources of adaptive evolution VL - 284 ER - TY - JOUR AB - A novel strategy for controlling the spread of arboviral diseases such as dengue, Zika and chikungunya is to transform mosquito populations with virus-suppressing Wolbachia. In general, Wolbachia transinfected into mosquitoes induce fitness costs through lower viability or fecundity. These maternally inherited bacteria also produce a frequency-dependent advantage for infected females by inducing cytoplasmic incompatibility (CI), which kills the embryos produced by uninfected females mated to infected males. These competing effects, a frequency-dependent advantage and frequency-independent costs, produce bistable Wolbachia frequency dynamics. Above a threshold frequency, denoted pˆ, CI drives fitness-decreasing Wolbachia transinfections through local populations; but below pˆ, infection frequencies tend to decline to zero. If pˆ is not too high, CI also drives spatial spread once infections become established over sufficiently large areas. We illustrate how simple models provide testable predictions concerning the spatial and temporal dynamics of Wolbachia introductions, focusing on rate of spatial spread, the shape of spreading waves, and the conditions for initiating spread from local introductions. First, we consider the robustness of diffusion-based predictions to incorporating two important features of wMel-Aedes aegypti biology that may be inconsistent with the diffusion approximations, namely fast local dynamics induced by complete CI (i.e., all embryos produced from incompatible crosses die) and long-tailed, non-Gaussian dispersal. With complete CI, our numerical analyses show that long-tailed dispersal changes wave-width predictions only slightly; but it can significantly reduce wave speed relative to the diffusion prediction; it also allows smaller local introductions to initiate spatial spread. Second, we use approximations for pˆ and dispersal distances to predict the outcome of 2013 releases of wMel-infected Aedes aegypti in Cairns, Australia, Third, we describe new data from Ae. aegypti populations near Cairns, Australia that demonstrate long-distance dispersal and provide an approximate lower bound on pˆ for wMel in northeastern Australia. Finally, we apply our analyses to produce operational guidelines for efficient transformation of vector populations over large areas. We demonstrate that even very slow spatial spread, on the order of 10-20 m/month (as predicted), can produce area-wide population transformation within a few years following initial releases covering about 20-30% of the target area. AU - Turelli, Michael AU - Barton, Nicholas H ID - 952 JF - Theoretical Population Biology SN - 00405809 TI - Deploying dengue-suppressing Wolbachia: Robust models predict slow but effective spatial spread in Aedes aegypti VL - 115 ER - TY - JOUR AB - Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100–200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transfo AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 951 IS - 5 JF - PLoS Biology SN - 15449173 TI - Local introduction and heterogeneous spatial spread of dengue-suppressing Wolbachia through an urban population of Aedes Aegypti VL - 15 ER - TY - GEN AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 9858 TI - Excel file with data on mosquito densities, Wolbachia infection status and housing characteristics ER - TY - GEN AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 9857 TI - Supporting information concerning observed wMel frequencies and analyses of habitat variables ER - TY - GEN AU - Schmidt, Tom AU - Barton, Nicholas H AU - Rasic, Gordana AU - Turley, Andrew AU - Montgomery, Brian AU - Iturbe Ormaetxe, Inaki AU - Cook, Peter AU - Ryan, Peter AU - Ritchie, Scott AU - Hoffmann, Ary AU - O’Neill, Scott AU - Turelli, Michael ID - 9856 TI - Supporting Information concerning additional likelihood analyses and results ER - TY - JOUR AB - Frequency-independent selection is generally considered as a force that acts to reduce the genetic variation in evolving populations, yet rigorous arguments for this idea are scarce. When selection fluctuates in time, it is unclear whether frequency-independent selection may maintain genetic polymorphism without invoking additional mechanisms. We show that constant frequency-independent selection with arbitrary epistasis on a well-mixed haploid population eliminates genetic variation if we assume linkage equilibrium between alleles. To this end, we introduce the notion of frequency-independent selection at the level of alleles, which is sufficient to prove our claim and contains the notion of frequency-independent selection on haploids. When selection and recombination are weak but of the same order, there may be strong linkage disequilibrium; numerical calculations show that stable equilibria are highly unlikely. Using the example of a diallelic two-locus model, we then demonstrate that frequency-independent selection that fluctuates in time can maintain stable polymorphism if linkage disequilibrium changes its sign periodically. We put our findings in the context of results from the existing literature and point out those scenarios in which the possible role of frequency-independent selection in maintaining genetic variation remains unclear. AU - Novak, Sebastian AU - Barton, Nicholas H ID - 910 IS - 2 JF - Genetics TI - When does frequency-independent selection maintain genetic variation? VL - 207 ER - TY - JOUR AB - Moths and butterflies (Lepidoptera) usually have a pair of differentiated WZ sex chromosomes. However, in most lineages outside of the division Ditrysia, as well as in the sister order Trichoptera, females lack a W chromosome. The W is therefore thought to have been acquired secondarily. Here we compare the genomes of three Lepidoptera species (one Dytrisia and two non-Dytrisia) to test three models accounting for the origin of the W: (1) a Z-autosome fusion; (2) a sex chromosome turnover; and (3) a non-canonical mechanism (e.g., through the recruitment of a B chromosome). We show that the gene content of the Z is highly conserved across Lepidoptera (rejecting a sex chromosome turnover) and that very few genes moved onto the Z in the common ancestor of the Ditrysia (arguing against a Z-autosome fusion). Our comparative genomics analysis therefore supports the secondary acquisition of the Lepidoptera W by a non-canonical mechanism, and it confirms the extreme stability of well-differentiated sex chromosomes. AU - Fraisse, Christelle AU - Picard, Marion A AU - Vicoso, Beatriz ID - 614 IS - 1 JF - Nature Communications SN - 20411723 TI - The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W VL - 8 ER - TY - JOUR AB - Mutator strains are expected to evolve when the availability and effect of beneficial mutations are high enough to counteract the disadvantage from deleterious mutations that will inevitably accumulate. As the population becomes more adapted to its environment, both availability and effect of beneficial mutations necessarily decrease and mutation rates are predicted to decrease. It has been shown that certain molecular mechanisms can lead to increased mutation rates when the organism finds itself in a stressful environment. While this may be a correlated response to other functions, it could also be an adaptive mechanism, raising mutation rates only when it is most advantageous. Here, we use a mathematical model to investigate the plausibility of the adaptive hypothesis. We show that such a mechanism can be mantained if the population is subjected to diverse stresses. By simulating various antibiotic treatment schemes, we find that combination treatments can reduce the effectiveness of second-order selection on stress-induced mutagenesis. We discuss the implications of our results to strategies of antibiotic therapy. AU - Lukacisinova, Marta AU - Novak, Sebastian AU - Paixao, Tiago ID - 696 IS - 7 JF - PLoS Computational Biology SN - 1553734X TI - Stress induced mutagenesis: Stress diversity facilitates the persistence of mutator genes VL - 13 ER - TY - JOUR AB - A central issue in cell biology is the physico-chemical basis of organelle biogenesis in intracellular trafficking pathways, its most impressive manifestation being the biogenesis of Golgi cisternae. At a basic level, such morphologically and chemically distinct compartments should arise from an interplay between the molecular transport and chemical maturation. Here, we formulate analytically tractable, minimalist models, that incorporate this interplay between transport and chemical progression in physical space, and explore the conditions for de novo biogenesis of distinct cisternae. We propose new quantitative measures that can discriminate between the various models of transport in a qualitative manner-this includes measures of the dynamics in steady state and the dynamical response to perturbations of the kind amenable to live-cell imaging. AU - Sachdeva, Himani AU - Barma, Mustansir AU - Rao, Madan ID - 1172 JF - Scientific Reports TI - Nonequilibrium description of de novo biogenesis and transport through Golgi-like cisternae VL - 6 ER - TY - JOUR AB - The genetic analysis of experimentally evolving populations typically relies on short reads from pooled individuals (Pool-Seq). While this method provides reliable allele frequency estimates, the underlying haplotype structure remains poorly characterized. With small population sizes and adaptive variants that start from low frequencies, the interpretation of selection signatures in most Evolve and Resequencing studies remains challenging. To facilitate the characterization of selection targets, we propose a new approach that reconstructs selected haplotypes from replicated time series, using Pool-Seq data. We identify selected haplotypes through the correlated frequencies of alleles carried by them. Computer simulations indicate that selected haplotype-blocks of several Mb can be reconstructed with high confidence and low error rates, even when allele frequencies change only by 20% across three replicates. Applying this method to real data from D. melanogaster populations adapting to a hot environment, we identify a selected haplotype-block of 6.93 Mb. We confirm the presence of this haplotype-block in evolved populations by experimental haplotyping, demonstrating the power and accuracy of our haplotype reconstruction from Pool-Seq data. We propose that the combination of allele frequency estimates with haplotype information will provide the key to understanding the dynamics of adaptive alleles. AU - Franssen, Susan AU - Barton, Nicholas H AU - Schlötterer, Christian ID - 1195 IS - 1 JF - Molecular Biology and Evolution TI - Reconstruction of haplotype-blocks selected during experimental evolution. VL - 34 ER - TY - JOUR AB - Sexual dimorphism in resource allocation is expected to change during the life cycle of dioecious plants because of temporal differences between the sexes in reproductive investment. Given the potential for sex-specific differences in reproductive costs, resource availability may contribute to variation in reproductive allocation in females and males. Here, we used Rumex hastatulus, a dioecious, wind-pollinated annual plant, to investigate whether sexual dimorphism varies with life-history stage and nutrient availability, and determine whether allocation patterns differ depending on reproductive commitment. To examine if the costs of reproduction varied between the sexes, reproduction was either allowed or prevented through bud removal, and biomass allocation was measured at maturity. In a second experiment to assess variation in sexual dimorphism across the life cycle, and whether this varied with resource availability, plants were grown in high and low nutrients and allocation to roots, aboveground vegetative growth and reproduction were measured at three developmental stages. Males prevented from reproducing compensated with increased above- and belowground allocation to a much larger degree than females, suggesting that male reproductive costs reduce vegetative growth. The proportional allocation to roots, reproductive structures and aboveground vegetative growth varied between the sexes and among life-cycle stages, but not with nutrient treatment. Females allocated proportionally more resources to roots than males at peak flowering, but this pattern was reversed at reproductive maturity under low-nutrient conditions. Our study illustrates the importance of temporal dynamics in sex-specific resource allocation and provides support for high male reproductive costs in wind-pollinated plants. AU - Teitel, Zachary AU - Pickup, Melinda AU - Field, David AU - Barrett, Spencer ID - 1224 IS - 1 JF - Plant Biology TI - The dynamics of resource allocation and costs of reproduction in a sexually dimorphic, wind-pollinated dioecious plant VL - 18 ER -