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Biology subjects

Barton, N. H.

Publications and source records attributed to Barton, N. H..

At least 19 recordsLinked to original sources

Introgression under linear selection on continuous genomes

We model the introgression of a small block that carries many weakly selected linked loci into a large homogeneous population, under the simple assumption that a block of introduced genome has a selective effect proportional to its map length. Using a diffusion approximation, we compute the probability that some part of the initial block survives the initial phase of the introgression and give the typical length of the surviving blocks. Our results quantify the effect of recombination on selection and drift during an introgression and indicate that the fate of the block depends on the strength of selection relative to recombination. When selection is positive some parts of the block are able to survive at large times, but large blocks can only persist if selection is stronger than recombination. Surprisingly, the probability of such a successful introgression is independent of the strength of recombination and is the same as that for a single beneficial allele. (This is not true of other quantities.) Conversely, a deleterious or neutral block is eventually lost, but at a much slower rate than a single allele with the same selective effect. In this case, surviving blocks are very small. We also consider the introgression of a block of genome made of a single beneficial allele linked to a deleterious background and compute the amount of deleterious material that hitchhikes during fixation.

evolutionary biology↗

Extreme long-range migration distorts flower colour clines in an Antirrhinum hybrid zone

Hybrid zones are natural laboratories for the study of speciation, allowing researchers to quantify selection, dispersal, and barriers to gene flow in the real world. We analyzed a flower-colour hybrid zone between two varieties of the common snapdragon, Antirrhinum majus subspecies majus, based on a dataset of 22,494 individuals sampled over 10 consecutive years (Field et al. in prep). We found narrow geographic clines at six SNP markers that are tightly linked to known flower colour loci, with widths ranging from 0.8 to 5.5 km. The clines have a stepped shape, which is expected when strong linkage disequilibrium generated by diffusive dispersal into the hybrid zone, increases the effective selection at the cline centre. However, the observed LD (mean [Formula]) was far too weak to explain the stepped cline shapes. Instead, we show that the stepped clines are shaped primarily by the observed long-distance dispersal. We used a novel simulation framework that accounts for realistic dispersal and multilocus selection to estimate the direct selection (1.5% to 18.5%) and indirect selection due to LD (1.2% to 2.4%) on each colour locus. Finally, we show that the barrier to the flow of neutral alleles through diffusive dispersal causes negligible distortion to the clines, while the reduction in gene flow due to selection on long-range migrants is substantial ([~]50%). The results shed new light onto the processes that shape hybrid zones, and highlight the need to account for the effects of realistic dispersal in theoretical and empirical studies of hybrid zones.

genetics↗

Evolution and information content of optimal gene regulatory architectures

Evolution of gene regulatory sequences is shaped by their genotype-phenotype (GP) map, but this map itself can evolve via changes in the molecular machinery that reads out the regulatory sequences. Using population genetics theory, we derive an optimality principle, implying that the evolved GP maps will associate fit phenotypes with larger numbers of possible genotypes. Mathematically, this builds on analogies between population genetics and statistical physics, as well as optimal coding in information theory. The results are particularly interesting in the context of transcriptional regulation, where optimal values of certain parameters that determine the gene regulatory architecture can be derived even without a complete knowledge of the molecular mechanisms involved. We illustrate the theory using a simplified model of transcription factor (TF) binding to cis-regulatory elements (CREs): the fraction of possible CREs across the entire genotype space that bind a given TF evolves to match the fraction of CREs under selection to bind that TF. Similar "frequency matching" results are expected to emerge generically, because selection implicitly optimizes the entire regulatory architecture that determines the "replicated GP map" for all CREs, while it simultaneously adapts towards individually fit CREs on that GP map. We discuss the subtleties and limitations of the theory related to biophysical constraints and the need for mutational robustness. Lastly, our theory suggests a possible mathematical definition for evolvability with predictive power that can be tested in evolutionary simulations and, ultimately, in comparative genetics studies.

evolutionary biology↗

Local adaptation in a metapopulation - a multi-habitat perspective

This study extends existing soft selection models of local adaptation in metapopulations from two habitats to a multi-habitat scenario, where each habitat exerts unique selection pressures. Specifically, we examine a three-habitat multilocus model in which each allele is favored in habitat 1, disfavored in habitat 3, and the selection pressure in the intermediate habitat may be different across loci. Employing the diffusion and fixed state approximations under the assumption of linkage equilibrium, we investigate conditions for the persistence of a polymorphism. We derive analytical thresholds for such persistence, which reveal scaling for the model parameters, local deme size (N), migration rate(m), selection pressure (si) and the proportion, (i) of each habitat. We show that under the assumption of infinitely many islands and selective neutrality in the intermediate habitat, the size of the intermediate habitat does not affect the maintenance of polymorphism. With symmetric selection pressure (s1=s3=s) in habitats 1 and 3, the system can be fully characterized by the product Ns, the product Nm, and a parameter {beta}, defined as the ratio of the size of habitat 1 (favoring the allele) to habitat 3 (where the allele is disfavored). We find that the range of polymorphism widens as gene flow between demes decreases and the symmetry of habitats increases ({beta} approaches 1). In the final section, we explore the effect of drift on the critical migration threshold as well as the effect of symmetry between selection. We demonstrate that genetic drift considerably lowers the critical migration threshold required for the maintenance of polymorphism. Furthermore, when each island is small but there are (infinitely) many of them, relatively low levels of gene flow can have a large impact in preventing genetic differentiation in a fragmented population.

evolutionary biology↗

Genealogical analysis of replicate flower colour hybrid zones in Antirrhinum

A major goal of speciation research is identifying loci that underpin barriers to gene flow. Population genomics takes a bottom-up approach, scanning the genome for molecular signatures of processes that drive or maintain divergence. However, interpreting the genomic landscape of speciation is complicated, because genome scans conflate multiple processes, most of which are not informative about gene flow. However, studying replicated population contrasts, including multiple incidences of secondary contact, can strengthen inferences. In this paper, we use linked-read sequencing (haplotagging), FST scans, and genealogical methods to characterise the genomic landscape associated with replicate hybrid zone formation. We studied two flower colour varieties of the common snapdragon, Antirrhinum majus subspecies majus, that form secondary hybrid zones in multiple independent valleys in the Pyrenees. Consistent with past work, we found very low differentiation at one well-studied zone (Planoles). However, at a second zone (Avallenet), we found stronger differentiation and greater heterogeneity, which we argue is due to differences in the amount of introgression following secondary contact. Topology weighting of genealogical trees identified loci where haplotype diversity was associated with the two snapdragon varieties. Two of the strongest associations were at previously identified flower colour loci: Flavia, that affects yellow pigmentation, and Rosea/Eluta, two linked loci that affect magenta pigmentation. Preliminary analysis of coalescence times provides additional evidence for selective sweeps at these loci and barriers to gene flow. Our study highlights the impact of demographic history on the differentiation landscape, emphasizing the need to distinguish between historical divergence and recent introgression.

evolutionary biology↗

Sign epistasis extends the effects of balancing selection on genetic diversity

Balancing selection, a form of selection that maintains genetic diversity, is difficult to detect, and the importance of balancing selection for the maintenance of genetic variation may be larger than often assumed. We model the possibility that the diversity-promoting effects of balancing selection extend to other loci that show sign epistasis with a locus under balancing selection. Rather than focusing on overdominance, as was done in previous efforts, we explore the effects of negative frequency dependence and show that this has important effects on the conditions under which the diversity-promoting effect of epistasis can occur in diploids. Our results show that not only recombination rate but also the dominance of sign epistasis are key parameters that determine the maintenance of polymorphism beyond the locus under direct balancing selection. We suggest that the effect we explore may play a significant role, especially when balancing selection acts on major effect loci.

evolutionary biology↗

Genome-wide cline analysis identifies new locus contributing to a barrier to gene flow across an Antirrhinum hybrid zone

Identification of the genomic regions that contribute to reproductive isolation and how they interact is a major goal of evolutionary genetics. Much effort has focused on locating candidate genes and potential barrier loci by scanning genomes for regions of excess differentiation (FST). An alternative, and perhaps more robust approach, would be to scan for genomic regions exhibiting steep clines in allele frequency across a hybrid zone. Here we develop this approach and apply it to genomic data from across a hybrid zone between varieties of Antirrhinum majus subspecies majus with different flower colour patterns (A. m. m var. pseudomajus and A. m. m var. striatum). Most steep clines are clustered in seven genomic regions, only four of which were present from FST scans between all pair-wise comparisons. Six of these regions carry previously identified loci that influence flower colour in the hybrid zone. The seventh region harbours a novel locus, RUBIA, modifying magenta intensity. Clines at RUBIA approached towards fixation on magenta side of the hybrid zone, whilst remaining polymorphic on the yellow side. This polymorphism on the yellow side may reflect a smaller phenotypic effect of RUBIA in yellow compared to magenta genetic backgrounds. Our findings illustrate how whole-genome cline scans in hybrid zones can robustly detect genomic regions contributing to phenotypic differences and highlight how different reproductive barrier loci interact across the genome.

evolutionary biology↗

Joint estimation of paternity, sibships and pollen dispersal in a snapdragon hybrid zone

1Inferring genealogical relationships of wild populations is useful because it gives direct estimates of mating patterns and variance in reproductive success. Inference can be improved by including information about parentage shared between siblings, or by modelling pheno-types or population data related to mating. However, we currently lack a framework to infer parent-offspring relationships, sibships, and population parameters in a single analysis. To address this we here extend a previous method Fractional Analysis of Paternity and Sibships to include population data for the case where one parent is known. We illustrate this with the example of pollen dispersal in a natural hybrid zone population of the snapdragon Antirrhinum majus. Pollen dispersal is leptokurtic, with half of mating events occurring within 30m, but with a long tail of mating events up to 859m. Using simulations we find that both sibship and population information substantially improve pedigree reconstruction, and that we can expect to resolve median dispersal distances with high accuracy.

evolutionary biology↗

Predicting rapid adaptation in time from adaptation in space: a 30-year field experiment in marine snails

Predicting the outcomes of adaptation is a major goal of evolutionary biology. When temporal changes in the environment mirror spatial gradients, it opens up the potential for predicting the course of adaptive evolution over time based on patterns of spatial genetic and phenotypic variation. We assessed this approach in a 30-year transplant experiment in the marine snail Littorina saxatilis. In 1992, snails were transplanted from a predation-dominated environment to one dominated by wave action. Based on spatial patterns, we predicted transitions in shell size and morphology, allele frequencies at positions throughout the genome, and chromosomal rearrangement frequencies. Observed changes closely agreed with predictions. Hence, transformation can be both dramatic and rapid, and predicted from knowledge of the phenotypic and genetic variation among populations.

evolutionary biology↗

Limits to selection on standing variation in an asexual population

We consider how a population responds to directional selection on standing variation, with no new variation from recombination or mutation. Initially, there are N individuals with trait values z1, ..., zN ; the fitness of individual i is proportional to [Formula]. The initial values are drawn from a distribution{psi} with variance V0; we give examples of the Laplace and Gaussian distributions. When selection is weak relative to drift [Formula], variance decreases exponentially at rate 1/N ; since the increase in mean in any generation equals the variance, the expected net change is just NV0, which is the same as Robertsons (1960) prediction for a sexual population. In contrast, when selection is strong relative to drift [Formula], the net change can be found by approximating the establishment of alleles by a branching process in which each allele competes independently with the population mean and the fittest allele to establish is certain to fix. Then, if the probability of survival to time [Formula] of an allele with value z is P (z), with mean [Formula], the winning allele is the fittest of [Formula] survivors drawn from a distribution [Formula]. When N is large, there is a scaling limit which depends on a single parameter [Formula]; the expecte d ultimate change is [Formula] for a Gaussian distribution, and [Formula] for a Laplace distribution (where [W]is the product log function). This approach also reveals the variability of the process, and its dynamics; we show that in the strong selection regime, the expected genetic variance decreases as [~] t-3 at large times. We discuss how these results may be related to selection on standing variation that is spread along a linear chromosome.

evolutionary biology↗

Accumulation and maintenance of information in evolution

Selection accumulates information in the genome -- it guides stochastically evolving populations towards states (geno-type frequencies) that would be unlikely under neutrality. This can be quantified as the Kullback-Leibler (KL) divergence between the actual distribution of genotype frequencies and the corresponding neutral distribution. First, we show that this population-level information sets an upper bound on the information at the level of genotype and phenotype, limiting how precisely they can be specified by selection. Next, we study how the accumulation and maintenance of information is limited by the cost of selection, measured as the genetic load or the relative fitness variance, both of which we connect to the control-theoretic KL cost of control. The information accumulation rate is upper bounded by the population size times the cost of selection. This bound is very general, and applies across models (Wright-Fisher, Moran, diffusion) and to arbitrary forms of selection, mutation and recombination. Finally, the cost of maintaining information depends on how it is encoded: specifying a single allele out of two is expensive, but one bit encoded among many weakly specified loci (as in a polygenic trait) is cheap.

evolutionary biology↗

The response of a metapopulation to a changing environment

A species distributed across diverse environments may adapt to local conditions. We ask how quickly such a species changes its range in response to changed conditions. Szep et al (Evolution, 2021) used the infinite island model to find the stationary distribution of allele frequencies and deme sizes. We extend this to find how a metapopulation responds to changes in carrying capacity, selection strength, or migration rate when deme sizes are fixed. We further develop a "fixed-state" approximation. Under this approximation, polymorphism is only possible for a narrow range of habitat proportions when selection is weak compared to drift, but for a much wider range otherwise. When rates of selection or migration relative to drift change in a single deme of the metapopulation, the population takes a time of order 1/m to reach the new equilibrium. However, even with many loci, there can be substantial fluctuations in net adaptation, because at each locus, alleles randomly get lost or fixed. Thus, in a finite metapopulation, variation may gradually be lost by chance, even if it would persist in an infinite metapopulation. When conditions change across the whole metapopulation, there can be rapid change, which is predicted well by the fixed-state approximation.

evolutionary biology↗

Genetic load and extinction in peripheral populations: the roles of migration, drift and demographic stochasticity

We analyse how migration from a large mainland influences genetic load and population numbers on an island, in a scenario where fitness-affecting variants are unconditionally deleterious, and where numbers decline with increasing load. Our analysis shows that migration can have qualitatively different effects, depending on the total mutation target and fitness effects of deleterious variants. In particular, we find that populations exhibit a genetic Allee effect across a wide range of parameter combinations, when variants are partially recessive, cycling between low-load (large-population) and high-load (sink) states. Increased migration reduces load in the sink state (by increasing heterozygosity) but further inflates load in the large-population state (by hindering purging). We identify various critical parameter thresholds at which one or other stable state collapses, and discuss how these thresholds are influenced by the genetic vs. demographic effects of migration. Our analysis is based on a semi-deterministic analysis, which accounts for genetic drift but neglects demographic stochasticity. We also compare against simulations which account for both demographic stochasticity and drift. Our results clarify the importance of gene flow as a key determinant of extinction risk in peripheral populations, even in the absence of ecological gradients.

evolutionary biology↗

Polygenic local adaptation in metapopulations: a stochastic eco-evolutionary model

This paper analyses the conditions for local adaptation in a metapopulation with infinitely many islands under a model of hard selection, where population size depends on local fitness. Each island belongs to one of two distinct ecological niches or habitats. Fitness is influenced by an additive trait which is under habitat-dependent directional selection. Our analysis is based on the diffusion approximation and accounts for both genetic drift and demographic stochasticity. By neglecting linkage disequilibria, it yields the joint distribution of allele frequencies and population size on each island. We find that under hard selection, the conditions for local adaptation in a rare habitat are more restrictive for more polygenic traits: even moderate migration load per locus at very many loci is sufficient for population sizes to decline. This further reduces the efficacy of selection at individual loci due to increased drift and because smaller populations are more prone to swamping due to migration, causing a positive feedback between increasing maladaptation and declining population sizes. Our analysis also highlights the importance of demographic stochasticity, which exacerbates the decline in numbers of maladapted populations, leading to population collapse in the rare habitat at significantly lower migration than predicted by deterministic arguments.

evolutionary biology↗

Haplotype tagging reveals parallel formation of hybrid races in two butterfly species

Genetic variation segregates as linked sets of variants, or haplotypes. Haplotypes and linkage are central to genetics and underpin virtually all genetic and selection analysis. And yet, genomic data often lack haplotype information, due to constraints in sequencing technologies. Here we present "haplotagging", a simple, low-cost linked-read sequencing technique that allows sequencing of hundreds of individuals while retaining linkage information. We apply haplotagging to construct megabase-size haplotypes for over 600 individual butterflies (Heliconius erato and H. melpomene), which form overlapping hybrid zones across an elevational gradient in Ecuador. Haplotagging identifies loci controlling distinctive high- and lowland wing color patterns. Divergent haplotypes are found at the same major loci in both species, while chromosome rearrangements show no parallelism. Remarkably, in both species the geographic clines for the major wing pattern loci are displaced by 18 km, leading to the rise of a novel hybrid morph in the centre of the hybrid zone. We propose that shared warning signalling (Mullerian mimicry) may couple the cline shifts seen in both species, and facilitate the parallel co-emergence of a novel hybrid morph in both co-mimetic species. Our results show the power of efficient haplotyping methods when combined with large-scale sequencing data from natural populations. One-sentence summaryHaplotagging, a novel linked-read sequencing technique that enables whole genome haplotyping in large populations, reveals the formation of a novel hybrid race in parallel hybrid zones of two co-mimicking Heliconius butterfly species through strikingly parallel divergences in their genomes.

evolutionary biology↗

The genomic and molecular basis of response to selection for longer limbs in mice

Evolutionary studies are often limited by missing data that are critical to understanding the history of selection. Selection experiments, which reproduce rapid evolution under controlled conditions, are excellent tools to study how genomes evolve under strong selection. Here we present a genomic dissection of the Longshanks selection experiment, in which mice were selectively bred over 20 generations for longer tibiae relative to body mass, resulting in 13% longer tibiae in two replicate lines. We synthesized evolutionary theory, genome sequences and molecular genetics to understand the selection response and found that it involved both polygenic adaptation and discrete loci of major effect, with the strongest loci likely to be selected in parallel between replicates. We show that selection may favor de-repression of bone growth through inactivation of two limb enhancers of an inhibitor, Nkx3-2. Our integrative genomic analyses thus show that it is possible to connect individual base-pair changes to the overall selection response.

evolutionary biology↗

Replicability of introgression under linked, polygenic selection

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.

evolutionary biology↗

Evolutionary pathways for the generation of new self-incompatibility haplotypes in a non-self recognition system

Self-incompatibility (SI) is a genetically based recognition system that functions to prevent self-fertilization and mating among related plants. An enduring puzzle in SI is how the high diversity observed in nature arises and is maintained. Based on the underlying recognition mechanism, SI can be classified into two main groups: self- and non-self recognition. Most work has focused on diversification within self-recognition systems despite expected differences between the two groups in the evolutionary pathways and outcomes of diversification. Here, we use a deterministic population genetic model and stochastic simulations to investigate how novel S-haplotypes evolve in a gametophytic non-self recognition (SRNase/S Locus F-box (SLF)) SI system. For this model the pathways for diversification involve either the maintenance or breakdown of SI and can vary in the order of mutations of the female (SRNase) and male (SLF) components. We show analytically that diversification can occur with high inbreeding depression and self-pollination, but this varies with evolutionary pathway and level of completeness (which determines the number of potential mating partners in the population), and in general is more likely for lower haplotype number. The conditions for diversification are broader in stochastic simulations of finite population size. However, the number of haplotypes observed under high inbreeding and moderate to high self-pollination is less than that commonly observed in nature. Diversification was observed through pathways that maintain SI as well as through self-compatible intermediates. Yet the lifespan of diversified haplotypes was sensitive to their level of completeness. By examining diversification in a non-self recognition SI system, this model extends our understanding of the evolution and maintenance of haplotype diversity observed in a recognition system common in flowering plants.

evolutionary biology↗