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 - DATA AB - The de novo genome assemblies generated for this study, and the associated metadata. AU - Fraisse, Christelle ID - 7163 TI - Supplementary Files for "The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W" 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 - TY - JOUR AB - How likely is it that a population escapes extinction through adaptive evolution? The answer to this question is of great relevance in conservation biology, where we aim at species’ rescue and the maintenance of biodiversity, and in agriculture and medicine, where we seek to hamper the emergence of pesticide or drug resistance. By reshuffling the genome, recombination has two antagonistic effects on the probability of evolutionary rescue: It generates and it breaks up favorable gene combinations. Which of the two effects prevails depends on the fitness effects of mutations and on the impact of stochasticity on the allele frequencies. In this article, we analyze a mathematical model for rescue after a sudden environmental change when adaptation is contingent on mutations at two loci. The analysis reveals a complex nonlinear dependence of population survival on recombination. We moreover find that, counterintuitively, a fast eradication of the wild type can promote rescue in the presence of recombination. The model also shows that two-step rescue is not unlikely to happen and can even be more likely than single-step rescue (where adaptation relies on a single mutation), depending on the circumstances. AU - Uecker, Hildegard AU - Hermisson, Joachim ID - 1241 IS - 2 JF - Genetics TI - The role of recombination in evolutionary rescue VL - 202 ER - TY - CONF AB - Crossing fitness valleys is one of the major obstacles to function optimization. In this paper we investigate how the structure of the fitness valley, namely its depth d and length ℓ, influence the runtime of different strategies for crossing these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis algorithm. While the (1+1) EA has to jump across the valley to a point of higher fitness because it does not accept decreasing moves, the non-elitist algorithms may cross the valley by accepting worsening moves. We show that while the runtime of the (1+1) EA algorithm depends critically on the length of the valley, the runtimes of the non-elitist algorithms depend crucially only on the depth of the valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of small length. Moreover, we show that both SSWM and Metropolis can also efficiently optimize a rugged function consisting of consecutive valleys. AU - Oliveto, Pietro AU - Paixao, Tiago AU - Heredia, Jorge AU - Sudholt, Dirk AU - Trubenova, Barbora ID - 1349 T2 - Proceedings of the Genetic and Evolutionary Computation Conference 2016 TI - When non-elitism outperforms elitism for crossing fitness valleys ER - TY - JOUR AB - The role of gene interactions in the evolutionary process has long been controversial. Although some argue that they are not of importance, because most variation is additive, others claim that their effect in the long term can be substantial. Here, we focus on the long-term effects of genetic interactions under directional selection assuming no mutation or dominance, and that epistasis is symmetrical overall. We ask by how much the mean of a complex trait can be increased by selection and analyze two extreme regimes, in which either drift or selection dominate the dynamics of allele frequencies. In both scenarios, epistatic interactions affect the long-term response to selection by modulating the additive genetic variance. When drift dominates, we extend Robertson ’ s [Robertson A (1960) Proc R Soc Lond B Biol Sci 153(951):234 − 249] argument to show that, for any form of epistasis, the total response of a haploid population is proportional to the initial total genotypic variance. In contrast, the total response of a diploid population is increased by epistasis, for a given initial genotypic variance. When selection dominates, we show that the total selection response can only be increased by epistasis when s ome initially deleterious alleles become favored as the genetic background changes. We find a sim- ple approximation for this effect and show that, in this regime, it is the structure of the genotype - phenotype map that matters and not the variance components of the population. AU - Paixao, Tiago AU - Barton, Nicholas H ID - 1359 IS - 16 JF - PNAS TI - The effect of gene interactions on the long-term response to selection VL - 113 ER - TY - JOUR AU - Barton, Nicholas H ID - 1356 IS - 1 JF - Genetics TI - Sewall Wright on evolution in Mendelian populations and the “Shifting Balance” VL - 202 ER - TY - JOUR AU - Barton, Nicholas H ID - 1357 IS - 3 JF - Genetics TI - Richard Hudson and Norman Kaplan on the coalescent process VL - 202 ER - TY - JOUR AU - Abbott, Richard AU - Barton, Nicholas H AU - Good, Jeffrey ID - 1409 IS - 11 JF - Molecular Ecology TI - Genomics of hybridization and its evolutionary consequences VL - 25 ER - TY - JOUR AB - Selection, mutation, and random drift affect the dynamics of allele frequencies and consequently of quantitative traits. While the macroscopic dynamics of quantitative traits can be measured, the underlying allele frequencies are typically unobserved. Can we understand how the macroscopic observables evolve without following these microscopic processes? This problem has been studied previously by analogy with statistical mechanics: the allele frequency distribution at each time point is approximated by the stationary form, which maximizes entropy. We explore the limitations of this method when mutation is small (4Nμ < 1) so that populations are typically close to fixation, and we extend the theory in this regime to account for changes in mutation strength. We consider a single diallelic locus either under directional selection or with overdominance and then generalize to multiple unlinked biallelic loci with unequal effects. We find that the maximum-entropy approximation is remarkably accurate, even when mutation and selection change rapidly. AU - Bod'ová, Katarína AU - Tkacik, Gasper AU - Barton, Nicholas H ID - 1420 IS - 4 JF - Genetics TI - A general approximation for the dynamics of quantitative traits VL - 202 ER - TY - JOUR AB - The inference of demographic history from genome data is hindered by a lack of efficient computational approaches. In particular, it has proved difficult to exploit the information contained in the distribution of genealogies across the genome. We have previously shown that the generating function (GF) of genealogies can be used to analytically compute likelihoods of demographic models from configurations of mutations in short sequence blocks (Lohse et al. 2011). Although the GF has a simple, recursive form, the size of such likelihood calculations explodes quickly with the number of individuals and applications of this framework have so far been mainly limited to small samples (pairs and triplets) for which the GF can be written by hand. Here we investigate several strategies for exploiting the inherent symmetries of the coalescent. In particular, we show that the GF of genealogies can be decomposed into a set of equivalence classes that allows likelihood calculations from nontrivial samples. Using this strategy, we automated blockwise likelihood calculations for a general set of demographic scenarios in Mathematica. These histories may involve population size changes, continuous migration, discrete divergence, and admixture between multiple populations. To give a concrete example, we calculate the likelihood for a model of isolation with migration (IM), assuming two diploid samples without phase and outgroup information. We demonstrate the new inference scheme with an analysis of two individual butterfly genomes from the sister species Heliconius melpomene rosina and H. cydno. AU - Lohse, Konrad AU - Chmelik, Martin AU - Martin, Simon AU - Barton, Nicholas H ID - 1518 IS - 2 JF - Genetics TI - Efficient strategies for calculating blockwise likelihoods under the coalescent VL - 202 ER - TY - JOUR AB - Ancestral processes are fundamental to modern population genetics and spatial structure has been the subject of intense interest for many years. Despite this interest, almost nothing is known about the distribution of the locations of pedigree or genetic ancestors. Using both spatially continuous and stepping-stone models, we show that the distribution of pedigree ancestors approaches a travelling wave, for which we develop two alternative approximations. The speed and width of the wave are sensitive to the local details of the model. After a short time, genetic ancestors spread far more slowly than pedigree ancestors, ultimately diffusing out with radius ## rather than spreading at constant speed. In contrast to the wave of pedigree ancestors, the spread of genetic ancestry is insensitive to the local details of the models. AU - Kelleher, Jerome AU - Etheridge, Alison AU - Véber, Amandine AU - Barton, Nicholas H ID - 1631 JF - Theoretical Population Biology TI - Spread of pedigree versus genetic ancestry in spatially distributed populations VL - 108 ER - TY - JOUR AB - Speciation results from the progressive accumulation of mutations that decrease the probability of mating between parental populations or reduce the fitness of hybrids—the so-called species barriers. The speciation genomic literature, however, is mainly a collection of case studies, each with its own approach and specificities, such that a global view of the gradual process of evolution from one to two species is currently lacking. Of primary importance is the prevalence of gene flow between diverging entities, which is central in most species concepts and has been widely discussed in recent years. Here, we explore the continuum of speciation thanks to a comparative analysis of genomic data from 61 pairs of populations/species of animals with variable levels of divergence. Gene flow between diverging gene pools is assessed under an approximate Bayesian computation (ABC) framework. We show that the intermediate "grey zone" of speciation, in which taxonomy is often controversial, spans from 0.5% to 2% of net synonymous divergence, irrespective of species life history traits or ecology. Thanks to appropriate modeling of among-locus variation in genetic drift and introgression rate, we clarify the status of the majority of ambiguous cases and uncover a number of cryptic species. Our analysis also reveals the high incidence in animals of semi-isolated species (when some but not all loci are affected by barriers to gene flow) and highlights the intrinsic difficulty, both statistical and conceptual, of delineating species in the grey zone of speciation. AU - Roux, Camille AU - Fraisse, Christelle AU - Romiguier, Jonathan AU - Anciaux, Youann AU - Galtier, Nicolas AU - Bierne, Nicolas ID - 1158 IS - 12 JF - PLoS Biology TI - Shedding light on the grey zone of speciation along a continuum of genomic divergence VL - 14 ER - TY - GEN AU - Roux, Camille AU - Fraisse, Christelle AU - Romiguier, Jonathan AU - Anciaux, Youann AU - Galtier, Nicolas AU - Bierne, Nicolas ID - 9862 TI - Simulation study to test the robustness of ABC in face of recent times of divergence ER - TY - GEN AU - Roux, Camille AU - Fraisse, Christelle AU - Romiguier, Jonathan AU - Anciaux, Youann AU - Galtier, Nicolas AU - Bierne, Nicolas ID - 9863 TI - Accessions of surveyed individuals, geographic locations and summary statistics ER - TY - THES AB - Natural environments are never constant but subject to spatial and temporal change on all scales, increasingly so due to human activity. Hence, it is crucial to understand the impact of environmental variation on evolutionary processes. In this thesis, I present three topics that share the common theme of environmental variation, yet illustrate its effect from different perspectives. First, I show how a temporally fluctuating environment gives rise to second-order selection on a modifier for stress-induced mutagenesis. Without fluctuations, when populations are adapted to their environment, mutation rates are minimized. I argue that a stress-induced mutator mechanism may only be maintained if the population is repeatedly subjected to diverse environmental challenges, and I outline implications of the presented results to antibiotic treatment strategies. Second, I discuss my work on the evolution of dispersal. Besides reproducing known results about the effect of heterogeneous habitats on dispersal, it identifies spatial changes in dispersal type frequencies as a source for selection for increased propensities to disperse. This concept contains effects of relatedness that are known to promote dispersal, and I explain how it identifies other forces selecting for dispersal and puts them on a common scale. Third, I analyse genetic variances of phenotypic traits under multivariate stabilizing selection. For the case of constant environments, I generalize known formulae of equilibrium variances to multiple traits and discuss how the genetic variance of a focal trait is influenced by selection on background traits. I conclude by presenting ideas and preliminary work aiming at including environmental fluctuations in the form of moving trait optima into the model. AU - Novak, Sebastian ID - 1125 SN - 2663-337X TI - Evolutionary proccesses in variable emvironments ER - TY - JOUR AB - Gene regulation relies on the specificity of transcription factor (TF)–DNA interactions. Limited specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to noncognate TF–DNA interactions or remains erroneously inactive. As each TF can have numerous interactions with noncognate cis-regulatory elements, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyse the effects of global crosstalk on gene regulation. We find that crosstalk presents a significant challenge for organisms with low-specificity TFs, such as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting at equilibrium, including variants of cooperativity and combinatorial regulation. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. AU - Friedlander, Tamar AU - Prizak, Roshan AU - Guet, Calin C AU - Barton, Nicholas H AU - Tkacik, Gasper ID - 1358 JF - Nature Communications TI - Intrinsic limits to gene regulation by global crosstalk VL - 7 ER - TY - GEN AB - Much of quantitative genetics is based on the ‘infinitesimal model’, under which selection has a negligible effect on the genetic variance. This is typically justified by assuming a very large number of loci with additive effects. However, it applies even when genes interact, provided that the number of loci is large enough that selection on each of them is weak relative to random drift. In the long term, directional selection will change allele frequencies, but even then, the effects of epistasis on the ultimate change in trait mean due to selection may be modest. Stabilising selection can maintain many traits close to their optima, even when the underlying alleles are weakly selected. However, the number of traits that can be optimised is apparently limited to ~4Ne by the ‘drift load’, and this is hard to reconcile with the apparent complexity of many organisms. Just as for the mutation load, this limit can be evaded by a particular form of negative epistasis. A more robust limit is set by the variance in reproductive success. This suggests that selection accumulates information most efficiently in the infinitesimal regime, when selection on individual alleles is weak, and comparable with random drift. A review of evidence on selection strength suggests that although most variance in fitness may be because of alleles with large Nes, substantial amounts of adaptation may be because of alleles in the infinitesimal regime, in which epistasis has modest effects. AU - Barton, Nicholas H ID - 9710 TI - Data from: How does epistasis influence the response to selection? ER - TY - GEN 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 ϕX174 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 - de Vladar, Harold AU - Włodarski, Tomasz AU - Bollback, Jonathan P ID - 9864 TI - Data from evolutionary interplay between structure, energy and epistasis in the coat protein of the ϕX174 phage family ER - TY - JOUR AB - Background and aims Angiosperms display remarkable diversity in flower colour, implying that transitions between pigmentation phenotypes must have been common. Despite progress in understanding transitions between anthocyanin (blue, purple, pink or red) and unpigmented (white) flowers, little is known about the evolutionary patterns of flower-colour transitions in lineages with both yellow and anthocyanin-pigmented flowers. This study investigates the relative rates of evolutionary transitions between different combinations of yellow- and anthocyanin-pigmentation phenotypes in the tribe Antirrhineae. Methods We surveyed taxonomic literature for data on anthocyanin and yellow floral pigmentation for 369 species across the tribe. We then reconstructed the phylogeny of 169 taxa and used phylogenetic comparative methods to estimate transition rates among pigmentation phenotypes across the phylogeny. Key Results In contrast to previous studies we found a bias towards transitions involving a gain in pigmentation, although transitions to phenotypes with both anthocyanin and yellow taxa are nevertheless extremely rare. Despite the dominance of yellow and anthocyanin-pigmented taxa, transitions between these phenotypes are constrained to move through a white intermediate stage, whereas transitions to double-pigmentation are very rare. The most abundant transitions are between anthocyanin-pigmented and unpigmented flowers, and similarly the most abundant polymorphic taxa were those with anthocyanin-pigmented and unpigmented flowers. Conclusions Our findings show that pigment evolution is limited by the presence of other floral pigments. This interaction between anthocyanin and yellow pigments constrains the breadth of potential floral diversity observed in nature. In particular, they suggest that selection has repeatedly acted to promote the spread of single-pigmented phenotypes across the Antirrhineae phylogeny. Furthermore, the correlation between transition rates and polymorphism suggests that the forces causing and maintaining variance in the short term reflect evolutionary processes on longer time scales. AU - Ellis, Thomas AU - Field, David ID - 1382 IS - 7 JF - Annals of Botany TI - Repeated gains in yellow and anthocyanin pigmentation in flower colour transitions in the Antirrhineae VL - 117 ER - TY - DATA AB - We collected flower colour information on species in the tribe Antirrhineae from taxonomic literature. We also retreived molecular data from GenBank for as many of these species as possible to estimate phylogenetic relationships among these taxa. We then used the R package 'diversitree' to examine patterns of evolutionary transitions between anthocyanin and yellow pigmentation across the phylogeny. For full details of the methods see: Ellis TJ and Field DL "Repeated gains in yellow and anthocyanin pigmentation in flower colour transitions in the Antirrhineae”, Annals of Botany (in press) AU - Ellis, Thomas AU - Field, David ID - 5550 TI - Flower colour data and phylogeny (NEXUS) files ER - TY - THES AB - Hybrid zones represent evolutionary laboratories, where recombination brings together alleles in combinations which have not previously been tested by selection. This provides an excellent opportunity to test the effect of molecular variation on fitness, and how this variation is able to spread through populations in a natural context. The snapdragon Antirrhinum majus is polymorphic in the wild for two loci controlling the distribution of yellow and magenta floral pigments. Where the yellow A. m. striatum and the magenta A. m. pseudomajus meet along a valley in the Spanish Pyrenees they form a stable hybrid zone Alleles at these loci recombine to give striking transgressive variation for flower colour. The sharp transition in phenotype over ~1km implies strong selection maintaining the hybrid zone. An indirect assay of pollinator visitation in the field found that pollinators forage in a positive-frequency dependent manner on Antirrhinum, matching previous data on fruit set. Experimental arrays and paternity analysis of wild-pollinated seeds demonstrated assortative mating for pigmentation alleles, and that pollinator behaviour alone is sufficient to explain this pattern. Selection by pollinators should be sufficiently strong to maintain the hybrid zone, although other mechanisms may be at work. At a broader scale I examined evolutionary transitions between yellow and anthocyanin pigmentation in the tribe Antirrhinae, and found that selection has acted strate that pollinators are a major determinant of reproductive success and mating patterns in wild Antirrhinum. AU - Ellis, Thomas ID - 1398 SN - 2663-337X TI - The role of pollinator-mediated selection in the maintenance of a flower color polymorphism in an Antirrhinum majus hybrid zone ER - TY - THES AB - Evolution of gene regulation is important for phenotypic evolution and diversity. Sequence-specific binding of regulatory proteins is one of the key regulatory mechanisms determining gene expression. Although there has been intense interest in evolution of regulatory binding sites in the last decades, a theoretical understanding is far from being complete. In this thesis, I aim at a better understanding of the evolution of transcriptional regulatory binding sequences by using biophysical and population genetic models. In the first part of the thesis, I discuss how to formulate the evolutionary dynamics of binding se- quences in a single isolated binding site and in promoter/enhancer regions. I develop a theoretical framework bridging between a thermodynamical model for transcription and a mutation-selection-drift model for monomorphic populations. I mainly address the typical evolutionary rates, and how they de- pend on biophysical parameters (e.g. binding length and specificity) and population genetic parameters (e.g. population size and selection strength). In the second part of the thesis, I analyse empirical data for a better evolutionary and biophysical understanding of sequence-specific binding of bacterial RNA polymerase. First, I infer selection on regulatory and non-regulatory binding sites of RNA polymerase in the E. coli K12 genome. Second, I infer the chemical potential of RNA polymerase, an important but unknown physical parameter defining the threshold energy for strong binding. Furthermore, I try to understand the relation between the lac promoter sequence diversity and the LacZ activity variation among 20 bacterial isolates by constructing a simple but biophysically motivated gene expression model. Lastly, I lay out a statistical framework to predict adaptive point mutations in de novo promoter evolution in a selection experiment. AU - Tugrul, Murat ID - 1131 SN - 2663-337X TI - Evolution of transcriptional regulatory sequences ER - TY - DATA AB - Genotypic, phenotypic and demographic data for 2128 wild snapdragons and 1127 open-pollinated progeny from a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted) February 2016). Tissue samples were sent to LGC Genomics in Berlin for DNA extraction, and genotyping at 70 SNP markers by KASPR genotyping. 29 of these SNPs failed to amplify reliably, and have been removed from this dataset. Other data were retreived from an online database of this population at www.antspec.org. AU - Field, David AU - Ellis, Thomas ID - 5553 KW - paternity assignment KW - pedigree KW - matting patterns KW - assortative mating KW - Antirrhinum majus KW - frequency-dependent selection KW - plant-pollinator interaction TI - Inference of mating patterns among wild snapdragons in a natural hybrid zone in 2012 ER - TY - DATA AB - Data from array experiments investigating pollinator behaviour on snapdragons in controlled conditions, and their effect on plant mating. Data were collected as part of Tom Ellis' PhD thesis , submitted February 2016. We placed a total of 36 plants in a grid inside a closed organza tent, with a single hive of commercially bred bumblebees (Bombus hortorum). We used only the yellow-flowered Antirrhinum majus striatum and the magenta-flowered Antirrhinum majus pseudomajus, at ratios of 6:36, 12:24, 18:18, 24:12 and 30:6. After 24 hours to learn how to deal with snapdragons, I observed pollinators foraging on plants, and recorded the transitions between plants. Thereafter seeds on plants were allowed to develops. A sample of these were grown to maturity when their flower colour could be determined, and they were scored as yellow, magenta, or hybrid. AU - Ellis, Thomas ID - 5551 TI - Data on pollinator observations and offpsring phenotypes ER - TY - DATA AB - Data on pollinator visitation to wild snapdragons in a natural hybrid zone, collected as part of Tom Ellis' PhD thesis (submitted February 2016). Snapdragon flowers have a mouth-like structure which pollinators must open to access nectar. We placed 5mm cellophane tags in these mouths, which are held in place by the pressure of the flower until a pollinator visits. When she opens the flower, the tag drops out, and one can infer a visit. We surveyed plants over multiple days in 2010, 2011 and 2012. Also included are data on phenotypic and demographic variables which may be explanatory variables for pollinator visitation. AU - Ellis, Thomas ID - 5552 TI - Pollinator visitation data for wild Antirrhinum majus plants, with phenotypic and frequency data. ER - TY - DATA AB - The data stored here is used in Murat Tugrul's PhD thesis (Chapter 3), which is related to the evolution of bacterial RNA polymerase binding. Magdalena Steinrueck (PhD Student in Calin Guet's group at IST Austria) performed the experiments and created the data on de novo promoter evolution. Fabienne Jesse (PhD Student in Jon Bollback's group at IST Austria) performed the experiments and created the data on lac promoter evolution. AU - Tugrul, Murat ID - 5554 KW - RNAP binding KW - de novo promoter evolution KW - lac promoter TI - Experimental Data for Binding Site Evolution of Bacterial RNA Polymerase ER - TY - CONF AB - Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired by natural evolution. In recent years the field of evolutionary computation has developed a rigorous analytical theory to analyse their runtime on many illustrative problems. Here we apply this theory to a simple model of natural evolution. In the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between occurrence of new mutations is much longer than the time it takes for a new beneficial mutation to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a (1+1)-type process where the probability of accepting a new genotype (improvements or worsenings) depends on the change in fitness. We present an initial runtime analysis of SSWM, quantifying its performance for various parameters and investigating differences to the (1+1) EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking advantage of information on the fitness gradient. AU - Paixao, Tiago AU - Sudholt, Dirk AU - Heredia, Jorge AU - Trubenova, Barbora ID - 1430 T2 - Proceedings of the 2015 Annual Conference on Genetic and Evolutionary Computation TI - First steps towards a runtime comparison of natural and artificial evolution ER - TY - JOUR AB - Evolutionary biologists have an array of powerful theoretical techniques that can accurately predict changes in the genetic composition of populations. Changes in gene frequencies and genetic associations between loci can be tracked as they respond to a wide variety of evolutionary forces. However, it is often less clear how to decompose these various forces into components that accurately reflect the underlying biology. Here, we present several issues that arise in the definition and interpretation of selection and selection coefficients, focusing on insights gained through the examination of selection coefficients in multilocus notation. Using this notation, we discuss how its flexibility-which allows different biological units to be identified as targets of selection-is reflected in the interpretation of the coefficients that the notation generates. In many situations, it can be difficult to agree on whether loci can be considered to be under "direct" versus "indirect" selection, or to quantify this selection. We present arguments for what the terms direct and indirect selection might best encompass, considering a range of issues, from viability and sexual selection to kin selection. We show how multilocus notation can discriminate between direct and indirect selection, and describe when it can do so. AU - Barton, Nicholas H AU - Servedio, Maria ID - 1519 IS - 5 JF - Evolution TI - The interpretation of selection coefficients VL - 69 ER - TY - JOUR AB - The theory of population genetics and evolutionary computation have been evolving separately for nearly 30 years. Many results have been independently obtained in both fields and many others are unique to its respective field. We aim to bridge this gap by developing a unifying framework for evolutionary processes that allows both evolutionary algorithms and population genetics models to be cast in the same formal framework. The framework we present here decomposes the evolutionary process into its several components in order to facilitate the identification of similarities between different models. In particular, we propose a classification of evolutionary operators based on the defining properties of the different components. We cast several commonly used operators from both fields into this common framework. Using this, we map different evolutionary and genetic algorithms to different evolutionary regimes and identify candidates with the most potential for the translation of results between the fields. This provides a unified description of evolutionary processes and represents a stepping stone towards new tools and results to both fields. AU - Paixao, Tiago AU - Badkobeh, Golnaz AU - Barton, Nicholas H AU - Çörüş, Doğan AU - Dang, Duccuong AU - Friedrich, Tobias AU - Lehre, Per AU - Sudholt, Dirk AU - Sutton, Andrew AU - Trubenova, Barbora ID - 1542 JF - Journal of Theoretical Biology TI - Toward a unifying framework for evolutionary processes VL - 383 ER - TY - JOUR AB - By hybridization and backcrossing, alleles can surmount species boundaries and be incorporated into the genome of a related species. This introgression of genes is of particular evolutionary relevance if it involves the transfer of adaptations between populations. However, any beneficial allele will typically be associated with other alien alleles that are often deleterious and hamper the introgression process. In order to describe the introgression of an adaptive allele, we set up a stochastic model with an explicit genetic makeup of linked and unlinked deleterious alleles. Based on the theory of reducible multitype branching processes, we derive a recursive expression for the establishment probability of the beneficial allele after a single hybridization event. We furthermore study the probability that slightly deleterious alleles hitchhike to fixation. The key to the analysis is a split of the process into a stochastic phase in which the advantageous alleles establishes and a deterministic phase in which it sweeps to fixation. We thereafter apply the theory to a set of biologically relevant scenarios such as introgression in the presence of many unlinked or few closely linked deleterious alleles. A comparison to computer simulations shows that the approximations work well over a large parameter range. AU - Uecker, Hildegard AU - Setter, Derek AU - Hermisson, Joachim ID - 1699 IS - 7 JF - Journal of Mathematical Biology TI - Adaptive gene introgression after secondary contact VL - 70 ER - TY - JOUR AB - Vegetation clearing and land-use change have depleted many natural plant communities to the point where restoration is required. A major impediment to the success of rebuilding complex vegetation communities is having regular access to sufficient quantities of high-quality seed. Seed-production areas (SPAs) can help generate this seed, but these must be underpinned by a broad genetic base to maximise the evolutionary potential of restored populations. However, genetic bottlenecks can occur at the collection, establishment and production stages in SPAs, requiring genetic evaluation. This is especially relevant for species that may take many years before a return on SPA investment is realised. Two recently established yellow box (Eucalyptus melliodora A.Cunn. ex Schauer, Myrtaceae) SPAs were evaluated to determine whether genetic bottlenecks had occurred between seed collection and SPA establishment. No evidence was found to suggest that a significant loss of genetic diversity had occurred at this stage, although there was a significant difference in diversity between the two SPAs. Complex population genetic structure was also observed in the seed used to source the SPAs, with up to eight groups identified. Plant survival in the SPAs was influenced by seed collection location but not by SPA location and was not associated with genetic diversity. There were also no associations between genetic diversity and plant growth. These data highlighted the importance of chance events when establishing SPAs and indicated that the two yellow box SPAs are likely to provide genetically diverse seed sources for future restoration projects, especially by pooling seed from both SPAs. AU - Broadhurst, Linda AU - Fifield, Graham AU - Vanzella, Bindi AU - Pickup, Melinda ID - 1703 IS - 5 JF - Australian Journal of Botany TI - An evaluation of the genetic structure of seed sources and the maintenance of genetic diversity during establishment of two yellow box (Eucalyptus melliodora) seed-production areas VL - 63 ER - TY - JOUR AB - Why do species not adapt to ever-wider ranges of conditions, gradually expanding their ecological niche and geographic range? Gene flow across environments has two conflicting effects: although it increases genetic variation, which is a prerequisite for adaptation, gene flow may swamp adaptation to local conditions. In 1956, Haldane proposed that, when the environment varies across space, "swamping" by gene flow creates a positive feedback between low population size and maladaptation, leading to a sharp range margin. However, current deterministic theory shows that, when variance can evolve, there is no such limit. Using simple analytical tools and simulations, we show that genetic drift can generate a sharp margin to a species' range, by reducing genetic variance below the level needed for adaptation to spatially variable conditions. Aided by separation of ecological and evolutionary timescales, the identified effective dimensionless parameters reveal a simple threshold that predicts when adaptation at the range margin fails. Two observable parameters determine the threshold: (i) the effective environmental gradient, which can be measured by the loss of fitness due to dispersal to a different environment; and (ii) the efficacy of selection relative to genetic drift. The theory predicts sharp range margins even in the absence of abrupt changes in the environment. Furthermore, it implies that gradual worsening of conditions across a species' habitat may lead to a sudden range fragmentation, when adaptation to a wide span of conditions within a single species becomes impossible. AU - Polechova, Jitka AU - Barton, Nicholas H ID - 1818 IS - 20 JF - PNAS TI - Limits to adaptation along environmental gradients VL - 112 ER - TY - JOUR AB - Entomopathogenic fungi are potent biocontrol agents that are widely used against insect pests, many of which are social insects. Nevertheless, theoretical investigations of their particular life history are scarce. We develop a model that takes into account the main distinguishing features between traditionally studied diseases and obligate killing pathogens, like the (biocontrol-relevant) insect-pathogenic fungi Metarhizium and Beauveria. First, obligate killing entomopathogenic fungi produce new infectious particles (conidiospores) only after host death and not yet on the living host. Second, the killing rates of entomopathogenic fungi depend strongly on the initial exposure dosage, thus we explicitly consider the pathogen load of individual hosts. Further, we make the model applicable not only to solitary host species, but also to group living species by incorporating social interactions between hosts, like the collective disease defences of insect societies. Our results identify the optimal killing rate for the pathogen that minimises its invasion threshold. Furthermore, we find that the rate of contact between hosts has an ambivalent effect: dense interaction networks between individuals are considered to facilitate disease outbreaks because of increased pathogen transmission. In social insects, this is compensated by their collective disease defences, i.e., social immunity. For the type of pathogens considered here, we show that even without social immunity, high contact rates between live individuals dilute the pathogen in the host colony and hence can reduce individual pathogen loads below disease-causing levels. AU - Novak, Sebastian AU - Cremer, Sylvia ID - 1850 IS - 5 JF - Journal of Theoretical Biology TI - Fungal disease dynamics in insect societies: Optimal killing rates and the ambivalent effect of high social interaction rates VL - 372 ER - TY - JOUR AB - We consider mating strategies for females who search for males sequentially during a season of limited length. We show that the best strategy rejects a given male type if encountered before a time-threshold but accepts him after. For frequency-independent benefits, we obtain the optimal time-thresholds explicitly for both discrete and continuous distributions of males, and allow for mistakes being made in assessing the correct male type. When the benefits are indirect (genes for the offspring) and the population is under frequency-dependent ecological selection, the benefits depend on the mating strategy of other females as well. This case is particularly relevant to speciation models that seek to explore the stability of reproductive isolation by assortative mating under frequency-dependent ecological selection. We show that the indirect benefits are to be quantified by the reproductive values of couples, and describe how the evolutionarily stable time-thresholds can be found. We conclude with an example based on the Levene model, in which we analyze the evolutionarily stable assortative mating strategies and the strength of reproductive isolation provided by them. AU - Priklopil, Tadeas AU - Kisdi, Eva AU - Gyllenberg, Mats ID - 1851 IS - 4 JF - Evolution SN - 0014-3820 TI - Evolutionarily stable mating decisions for sequentially searching females and the stability of reproductive isolation by assortative mating VL - 69 ER - TY - JOUR AB - We introduce a one-parametric family of tree growth models, in which branching probabilities decrease with branch age τ as τ-α. Depending on the exponent α, the scaling of tree depth with tree size n displays a transition between the logarithmic scaling of random trees and an algebraic growth. At the transition (α=1) tree depth grows as (logn)2. This anomalous scaling is in good agreement with the trend observed in evolution of biological species, thus providing a theoretical support for age-dependent speciation and associating it to the occurrence of a critical point. AU - Keller-Schmidt, Stephanie AU - Tugrul, Murat AU - Eguíluz, Víctor AU - Hernandez Garcia, Emilio AU - Klemm, Konstantin ID - 1883 IS - 2 JF - Physical Review E Statistical Nonlinear and Soft Matter Physics TI - Anomalous scaling in an age-dependent branching model VL - 91 ER - TY - JOUR AB - Background: Indirect genetic effects (IGEs) occur when genes expressed in one individual alter the expression of traits in social partners. Previous studies focused on the evolutionary consequences and evolutionary dynamics of IGEs, using equilibrium solutions to predict phenotypes in subsequent generations. However, whether or not such steady states may be reached may depend on the dynamics of interactions themselves. Results: In our study, we focus on the dynamics of social interactions and indirect genetic effects and investigate how they modify phenotypes over time. Unlike previous IGE studies, we do not analyse evolutionary dynamics; rather we consider within-individual phenotypic changes, also referred to as phenotypic plasticity. We analyse iterative interactions, when individuals interact in a series of discontinuous events, and investigate the stability of steady state solutions and the dependence on model parameters, such as population size, strength, and the nature of interactions. We show that for interactions where a feedback loop occurs, the possible parameter space of interaction strength is fairly limited, affecting the evolutionary consequences of IGEs. We discuss the implications of our results for current IGE model predictions and their limitations. AU - Trubenova, Barbora AU - Novak, Sebastian AU - Hager, Reinmar ID - 1809 IS - 5 JF - PLoS One TI - Indirect genetic effects and the dynamics of social interactions VL - 10 ER - TY - GEN AU - Trubenova, Barbora AU - Novak, Sebastian AU - Hager, Reinmar ID - 9772 TI - Description of the agent based simulations ER - TY - GEN AU - Tugrul, Murat AU - Paixao, Tiago AU - Barton, Nicholas H AU - Tkačik, Gašper ID - 9712 TI - Other fitness models for comparison & for interacting TFBSs ER - TY - GEN AU - Trubenova, Barbora AU - Novak, Sebastian AU - Hager, Reinmar ID - 9715 TI - Mathematical inference of the results ER -