@article{39, abstract = {We study how a block of genome with a large number of weakly selected loci introgresses under directional selection into a genetically homogeneous population. We derive exact expressions for the expected rate of growth of any fragment of the introduced block during the initial phase of introgression, and show that the growth rate of a single-locus variant is largely insensitive to its own additive effect, but depends instead on the combined effect of all loci within a characteristic linkage scale. The expected growth rate of a fragment is highly correlated with its long-term introgression probability in populations of moderate size, and can hence identify variants that are likely to introgress across replicate populations. We clarify how the introgression probability of an individual variant is determined by the interplay between hitchhiking with relatively large fragments during the early phase of introgression and selection on fine-scale variation within these, which at longer times results in differential introgression probabilities for beneficial and deleterious loci within successful fragments. By simulating individuals, we also investigate how introgression probabilities at individual loci depend on the variance of fitness effects, the net fitness of the introduced block, and the size of the recipient population, and how this shapes the net advance under selection. Our work suggests that even highly replicable substitutions may be associated with a range of selective effects, which makes it challenging to fine map the causal loci that underlie polygenic adaptation.}, author = {Sachdeva, Himani and Barton, Nicholas H}, issn = {0016-6731}, journal = {Genetics}, number = {4}, pages = {1411--1427}, publisher = {Genetics Society of America}, title = {{Replicability of introgression under linked, polygenic selection}}, doi = {10.1534/genetics.118.301429}, volume = {210}, year = {2018}, } @article{40, abstract = {Hanemaaijer et al. (Molecular Ecology, 27, 2018) describe the genetic consequences of the introgression of an insecticide resistance allele into a mosquito population. Linked alleles initially increased, but many of these later declined. It is hard to determine whether this decline was due to counter‐selection, rather than simply to chance.}, author = {Barton, Nicholas H}, issn = {1365-294X}, journal = {Molecular Ecology}, number = {24}, pages = {4973--4975}, publisher = {Wiley}, title = {{The consequences of an introgression event}}, doi = {10.1111/mec.14950}, volume = {27}, year = {2018}, } @article{423, abstract = {Herd immunity, a process in which resistant individuals limit the spread of a pathogen among susceptible hosts has been extensively studied in eukaryotes. Even though bacteria have evolved multiple immune systems against their phage pathogens, herd immunity in bacteria remains unexplored. Here we experimentally demonstrate that herd immunity arises during phage epidemics in structured and unstructured Escherichia coli populations consisting of differing frequencies of susceptible and resistant cells harboring CRISPR immunity. In addition, we develop a mathematical model that quantifies how herd immunity is affected by spatial population structure, bacterial growth rate, and phage replication rate. Using our model we infer a general epidemiological rule describing the relative speed of an epidemic in partially resistant spatially structured populations. Our experimental and theoretical findings indicate that herd immunity may be important in bacterial communities, allowing for stable coexistence of bacteria and their phages and the maintenance of polymorphism in bacterial immunity.}, author = {Payne, Pavel and Geyrhofer, Lukas and Barton, Nicholas H and Bollback, Jonathan P}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{CRISPR-based herd immunity can limit phage epidemics in bacterial populations}}, doi = {10.7554/eLife.32035}, volume = {7}, year = {2018}, } @article{430, abstract = {In this issue of GENETICS, a new method for detecting natural selection on polygenic traits is developed and applied to sev- eral human examples ( Racimo et al. 2018 ). By de fi nition, many loci contribute to variation in polygenic traits, and a challenge for evolutionary ge neticists has been that these traits can evolve by small, nearly undetectable shifts in allele frequencies across each of many, typically unknown, loci. Recently, a helpful remedy has arisen. Genome-wide associ- ation studies (GWAS) have been illuminating sets of loci that can be interrogated jointly for c hanges in allele frequencies. By aggregating small signal s of change across many such loci, directional natural selection is now in principle detect- able using genetic data, even for highly polygenic traits. This is an exciting arena of progress – with these methods, tests can be made for selection associated with traits, and we can now study selection in what may be its most prevalent mode. The continuing fast pace of GWAS publications suggest there will be many more polygenic tests of selection in the near future, as every new GWAS is an opportunity for an accom- panying test of polygenic selection. However, it is important to be aware of complications th at arise in interpretation, especially given that these studies may easily be misinter- preted both in and outside the evolutionary genetics commu- nity. Here, we provide context for understanding polygenic tests and urge caution regarding how these results are inter- preted and reported upon more broadly.}, author = {Novembre, John and Barton, Nicholas H}, journal = {Genetics}, number = {4}, pages = {1351 -- 1355}, publisher = {Genetics Society of America}, title = {{Tread lightly interpreting polygenic tests of selection}}, doi = {10.1534/genetics.118.300786}, volume = {208}, year = {2018}, } @article{1111, abstract = {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.}, author = {Heredia, Jorge and Trubenova, Barbora and Sudholt, Dirk and Paixao, Tiago}, issn = {0016-6731}, journal = {Genetics}, number = {2}, pages = {803 -- 825}, publisher = {Genetics Society of America}, title = {{Selection limits to adaptive walks on correlated landscapes}}, doi = {10.1534/genetics.116.189340}, volume = {205}, year = {2017}, } @inproceedings{1112, abstract = {There has been renewed interest in modelling the behaviour of evolutionary algorithms by more traditional mathematical objects, such as ordinary differential equations or Markov chains. The advantage is that the analysis becomes greatly facilitated due to the existence of well established methods. However, this typically comes at the cost of disregarding information about the process. Here, we introduce the use of stochastic differential equations (SDEs) for the study of EAs. SDEs can produce simple analytical results for the dynamics of stochastic processes, unlike Markov chains which can produce rigorous but unwieldy expressions about the dynamics. On the other hand, unlike ordinary differential equations (ODEs), they do not discard information about the stochasticity of the process. We show that these are especially suitable for the analysis of fixed budget scenarios and present analogs of the additive and multiplicative drift theorems for SDEs. We exemplify the use of these methods for two model algorithms ((1+1) EA and RLS) on two canonical problems(OneMax and LeadingOnes).}, author = {Paixao, Tiago and Pérez Heredia, Jorge}, booktitle = {Proceedings of the 14th ACM/SIGEVO Conference on Foundations of Genetic Algorithms}, isbn = {978-145034651-1}, location = {Copenhagen, Denmark}, pages = {3 -- 11}, publisher = {ACM}, title = {{An application of stochastic differential equations to evolutionary algorithms}}, doi = {10.1145/3040718.3040729}, year = {2017}, } @article{1169, abstract = {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.}, author = {Novak, Sebastian and Kollár, Richard}, issn = {0016-6731}, journal = {Genetics}, number = {1}, pages = {367 -- 374}, publisher = {Genetics Society of America}, title = {{Spatial gene frequency waves under genotype dependent dispersal}}, doi = {10.1534/genetics.116.193946}, volume = {205}, year = {2017}, } @article{1191, abstract = {Variation in genotypes may be responsible for differences in dispersal rates, directional biases, and growth rates of individuals. These traits may favor certain genotypes and enhance their spatiotemporal spreading into areas occupied by the less advantageous genotypes. We study how these factors influence the speed of spreading in the case of two competing genotypes under the assumption that spatial variation of the total population is small compared to the spatial variation of the frequencies of the genotypes in the population. In that case, the dynamics of the frequency of one of the genotypes is approximately described by a generalized Fisher–Kolmogorov–Petrovskii–Piskunov (F–KPP) equation. This generalized F–KPP equation with (nonlinear) frequency-dependent diffusion and advection terms admits traveling wave solutions that characterize the invasion of the dominant genotype. Our existence results generalize the classical theory for traveling waves for the F–KPP with constant coefficients. Moreover, in the particular case of the quadratic (monostable) nonlinear growth–decay rate in the generalized F–KPP we study in detail the influence of the variance in diffusion and mean displacement rates of the two genotypes on the minimal wave propagation speed.}, author = {Kollár, Richard and Novak, Sebastian}, journal = {Bulletin of Mathematical Biology}, number = {3}, pages = {525--559}, publisher = {Springer}, title = {{Existence of traveling waves for the generalized F–KPP equation}}, doi = {10.1007/s11538-016-0244-3}, volume = {79}, year = {2017}, } @article{1199, abstract = {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.}, author = {Barton, Nicholas H}, journal = {Heredity}, pages = {96 -- 109}, publisher = {Nature Publishing Group}, title = {{How does epistasis influence the response to selection?}}, doi = {10.1038/hdy.2016.109}, volume = {118}, year = {2017}, } @article{1336, abstract = {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 the runtimes of EAs 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 occurrences of new mutations is much longer than the time it takes for a mutated genotype to take over the population. In this situation, the population only contains copies of one genotype and evolution can be modelled as a stochastic process evolving one genotype by means of mutation and selection between the resident and the mutated genotype. The probability of accepting the mutated genotype then depends on the change in fitness. We study this process, SSWM, from an algorithmic perspective, quantifying its expected optimisation time for various parameters and investigating differences to a similar evolutionary algorithm, the well-known (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.}, author = {Paixao, Tiago and Pérez Heredia, Jorge and Sudholt, Dirk and Trubenova, Barbora}, issn = {0178-4617}, journal = {Algorithmica}, number = {2}, pages = {681 -- 713}, publisher = {Springer}, title = {{Towards a runtime comparison of natural and artificial evolution}}, doi = {10.1007/s00453-016-0212-1}, volume = {78}, year = {2017}, } @article{1351, abstract = {The behaviour of gene regulatory networks (GRNs) is typically analysed using simulation-based statistical testing-like methods. In this paper, we demonstrate that we can replace this approach by a formal verification-like method that gives higher assurance and scalability. We focus on Wagner’s weighted GRN model with varying weights, which is used in evolutionary biology. In the model, weight parameters represent the gene interaction strength that may change due to genetic mutations. For a property of interest, we synthesise the constraints over the parameter space that represent the set of GRNs satisfying the property. We experimentally show that our parameter synthesis procedure computes the mutational robustness of GRNs—an important problem of interest in evolutionary biology—more efficiently than the classical simulation method. We specify the property in linear temporal logic. We employ symbolic bounded model checking and SMT solving to compute the space of GRNs that satisfy the property, which amounts to synthesizing a set of linear constraints on the weights.}, author = {Giacobbe, Mirco and Guet, Calin C and Gupta, Ashutosh and Henzinger, Thomas A and Paixao, Tiago and Petrov, Tatjana}, issn = {0001-5903}, journal = {Acta Informatica}, number = {8}, pages = {765 -- 787}, publisher = {Springer}, title = {{Model checking the evolution of gene regulatory networks}}, doi = {10.1007/s00236-016-0278-x}, volume = {54}, year = {2017}, } @article{570, abstract = {Most phenotypes are determined by molecular systems composed of specifically interacting molecules. However, unlike for individual components, little is known about the distributions of mutational effects of molecular systems as a whole. We ask how the distribution of mutational effects of a transcriptional regulatory system differs from the distributions of its components, by first independently, and then simultaneously, mutating a transcription factor and the associated promoter it represses. We find that the system distribution exhibits increased phenotypic variation compared to individual component distributions - an effect arising from intermolecular epistasis between the transcription factor and its DNA-binding site. In large part, this epistasis can be qualitatively attributed to the structure of the transcriptional regulatory system and could therefore be a common feature in prokaryotes. Counter-intuitively, intermolecular epistasis can alleviate the constraints of individual components, thereby increasing phenotypic variation that selection could act on and facilitating adaptive evolution. }, author = {Lagator, Mato and Sarikas, Srdjan and Acar, Hande and Bollback, Jonathan P and Guet, Calin C}, issn = {2050-084X}, journal = {eLife}, publisher = {eLife Sciences Publications}, title = {{Regulatory network structure determines patterns of intermolecular epistasis}}, doi = {10.7554/eLife.28921}, volume = {6}, year = {2017}, } @article{611, abstract = {Small RNAs (sRNAs) regulate genes in plants and animals. Here, we show that population-wide differences in color patterns in snapdragon flowers are caused by an inverted duplication that generates sRNAs. The complexity and size of the transcripts indicate that the duplication represents an intermediate on the pathway to microRNA evolution. The sRNAs repress a pigment biosynthesis gene, creating a yellow highlight at the site of pollinator entry. The inverted duplication exhibits steep clines in allele frequency in a natural hybrid zone, showing that the allele is under selection. Thus, regulatory interactions of evolutionarily recent sRNAs can be acted upon by selection and contribute to the evolution of phenotypic diversity.}, author = {Bradley, Desmond and Xu, Ping and Mohorianu, Irina and Whibley, Annabel and Field, David and Tavares, Hugo and Couchman, Matthew and Copsey, Lucy and Carpenter, Rosemary and Li, Miaomiao and Li, Qun and Xue, Yongbiao and Dalmay, Tamas and Coen, Enrico}, issn = {0036-8075}, journal = {Science}, number = {6365}, pages = {925 -- 928}, publisher = {American Association for the Advancement of Science}, title = {{Evolution of flower color pattern through selection on regulatory small RNAs}}, doi = {10.1126/science.aao3526}, volume = {358}, year = {2017}, } @article{614, abstract = {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.}, author = {Fraisse, Christelle and Picard, Marion A and Vicoso, Beatriz}, issn = {2041-1723}, journal = {Nature Communications}, number = {1}, publisher = {Nature Publishing Group}, title = {{The deep conservation of the Lepidoptera Z chromosome suggests a non canonical origin of the W}}, doi = {10.1038/s41467-017-01663-5}, volume = {8}, year = {2017}, } @article{626, abstract = {Our focus here is on the infinitesimal model. In this model, one or several quantitative traits are described as the sum of a genetic and a non-genetic component, the first being distributed within families as a normal random variable centred at the average of the parental genetic components, and with a variance independent of the parental traits. Thus, the variance that segregates within families is not perturbed by selection, and can be predicted from the variance components. This does not necessarily imply that the trait distribution across the whole population should be Gaussian, and indeed selection or population structure may have a substantial effect on the overall trait distribution. One of our main aims is to identify some general conditions on the allelic effects for the infinitesimal model to be accurate. We first review the long history of the infinitesimal model in quantitative genetics. Then we formulate the model at the phenotypic level in terms of individual trait values and relationships between individuals, but including different evolutionary processes: genetic drift, recombination, selection, mutation, population structure, …. We give a range of examples of its application to evolutionary questions related to stabilising selection, assortative mating, effective population size and response to selection, habitat preference and speciation. We provide a mathematical justification of the model as the limit as the number M of underlying loci tends to infinity of a model with Mendelian inheritance, mutation and environmental noise, when the genetic component of the trait is purely additive. We also show how the model generalises to include epistatic effects. We prove in particular that, within each family, the genetic components of the individual trait values in the current generation are indeed normally distributed with a variance independent of ancestral traits, up to an error of order 1∕M. Simulations suggest that in some cases the convergence may be as fast as 1∕M.}, author = {Barton, Nicholas H and Etheridge, Alison and Véber, Amandine}, issn = {0040-5809}, journal = {Theoretical Population Biology}, pages = {50 -- 73}, publisher = {Academic Press}, title = {{The infinitesimal model: Definition derivation and implications}}, doi = {10.1016/j.tpb.2017.06.001}, volume = {118}, year = {2017}, } @phdthesis{6291, abstract = {Bacteria and their pathogens – phages – are the most abundant living entities on Earth. Throughout their coevolution, bacteria have evolved multiple immune systems to overcome the ubiquitous threat from the phages. Although the molecu- lar details of these immune systems’ functions are relatively well understood, their epidemiological consequences for the phage-bacterial communities have been largely neglected. In this thesis we employed both experimental and theoretical methods to explore whether herd and social immunity may arise in bacterial popu- lations. Using our experimental system consisting of Escherichia coli strains with a CRISPR based immunity to the T7 phage we show that herd immunity arises in phage-bacterial communities and that it is accentuated when the populations are spatially structured. By fitting a mathematical model, we inferred expressions for the herd immunity threshold and the velocity of spread of a phage epidemic in partially resistant bacterial populations, which both depend on the bacterial growth rate, phage burst size and phage latent period. We also investigated the poten- tial for social immunity in Streptococcus thermophilus and its phage 2972 using a bioinformatic analysis of potentially coding short open reading frames with a signalling signature, encoded within the CRISPR associated genes. Subsequently, we tested one identified potentially signalling peptide and found that its addition to a phage-challenged culture increases probability of survival of bacteria two fold, although the results were only marginally significant. Together, these results demonstrate that the ubiquitous arms races between bacteria and phages have further consequences at the level of the population.}, author = {Payne, Pavel}, issn = {2663-337X}, pages = {83}, publisher = {Institute of Science and Technology Austria}, title = {{Bacterial herd and social immunity to phages}}, year = {2017}, } @article{1063, abstract = {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.}, author = {Uecker, Hildegard}, issn = {0014-3820}, journal = {Evolution}, number = {4}, pages = {845 -- 858}, publisher = {Wiley}, title = {{Evolutionary rescue in randomly mating, selfing, and clonal populations}}, doi = {10.1111/evo.13191}, volume = {71}, year = {2017}, } @article{1074, abstract = {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.}, author = {Ringbauer, Harald and Coop, Graham and Barton, Nicholas H}, issn = {0016-6731}, journal = {Genetics}, number = {3}, pages = {1335 -- 1351}, publisher = {Genetics Society of America}, title = {{Inferring recent demography from isolation by distance of long shared sequence blocks}}, doi = {10.1534/genetics.116.196220}, volume = {205}, year = {2017}, } @article{910, abstract = {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. }, author = {Novak, Sebastian and Barton, Nicholas H}, journal = {Genetics}, number = {2}, pages = {653 -- 668}, publisher = {Genetics Society of America}, title = {{When does frequency-independent selection maintain genetic variation?}}, doi = {10.1534/genetics.117.300129}, volume = {207}, year = {2017}, } @article{952, abstract = {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.}, author = {Turelli, Michael and Barton, Nicholas H}, issn = {0040-5809}, journal = {Theoretical Population Biology}, pages = {45 -- 60}, publisher = {Elsevier}, title = {{Deploying dengue-suppressing Wolbachia: Robust models predict slow but effective spatial spread in Aedes aegypti}}, doi = {10.1016/j.tpb.2017.03.003}, volume = {115}, year = {2017}, }