Biology subjects

Hermisson, J.

Publications and source records attributed to Hermisson, J..

12 recordsLinked to original sources

bioRxiv2026

Effect of population structure and stabilizing selection on quantitative genetic variation

We study one of the simplest scenarios of polygenic selection that can be imagined: a subdivided population of diploid individuals expressing an additive trait under spatially homogeneous stabilizing selection. We are interested in the amounts of variation that can be maintained at mutation-selection-migration-drift equilibrium, at individual loci and at the level of the trait, within and among subpopulations. We derive analytical approximations for variance components and summary statistics such as FST and QST under the assumptions of the infinite-island model and compare these with individual-based simulations. We find that: (i) There is a critical migration threshold (which depends on effect sizes of trait loci) below which population structure strongly inflates genic variance in the subdivided population to levels well above those in a panmictic population. Variation within each subpopulation is maximized close to the critical migration rate. (ii) The genetic basis of trait variation across subpopulations is most similar close to this migration threshold and (counter-intuitively) becomes less similar for higher migration rates. This has consequences for the portability of Genome-Wide Association Studies (GWAS) between subpopulations, i.e, the extent to which loci with large contributions to variance in one subpopulation explain variance in other subpopulations. (iii) An analytical mean-field approach based on the single-locus diffusion approximation, together with effective migration and selection parameters (to account for associations between loci), very accurately predicts various quantities.

evolutionary biology↗

bioRxiv2023

A theory of oligogenic adaptation of a quantitative trait

Rapid phenotypic adaptation is widespread in nature, but the underlying genetic dynamics remain controversial. Whereas population genetics envisages sequential beneficial substitutions, quantitative genetics assumes a collective response through subtle shifts in allele frequencies. This dichotomy of a monogenic and a highly polygenic view of adaptation raises the question of a middle ground, as well as the factors controlling the transition. Here, we consider an additive quantitative trait with equal locus effects under Gaussian stabilizing selection that adapts to a new trait optimum after an environmental change. We present an analytical framework based on Yule branching processes to describe how phenotypic adaptation is achieved by collective changes in allele frequencies at the underlying loci. In particular, we derive an approximation for the joint allele-frequency distribution at threshold levels of the trait mean as a comprehensive descriptor of the adaptive architecture. Depending on the model parameters, this architecture reproduces the well-known patterns of sequential, monogenic sweeps, or of subtle, polygenic frequency shifts. Between these endpoints, we observe oligogenic architecture types that exhibit characteristic patterns of partial sweeps. We find that a single compound parameter, the population-scaled background mutation rate {Theta}bg, is the most important predictor of the type of adaptation, while selection strength, the number of loci in the genetic basis, and linkage only play a minor role.

evolutionary biology↗

bioRxiv2022

Modeling the genetic footprint of fluctuating balancing selection: From the local to the genomic scale

Natural selection not only affects the actual loci under selection but also leaves "footprints" in patterns of genetic variation in linked genetic regions. This offers exciting opportunities for inferring selection and for understanding the processes shaping levels of genetic variation in natural populations. Here we develop analytical approximations based on coalescent theory to characterize the genetic footprint of a complex, but potentially common type of natural selection: balancing selection with seasonally fluctuating allele frequencies. We show that seasonal allele frequency fluctuations can have important (and partly unexpected) consequences for the genetic footprint of balancing selection. As also confirmed by stochastic simulations, fluctuating balancing selection generally leads to an increase in genetic diversity close to the selected site, the effect of balancing selection, but reduces diversity further away from the selected site, which is a consequence of the allele-frequency fluctuations effectively producing recurrent bottlenecks of allelic backgrounds. This negative effect usually outweighs the positive effect when averaging diversity levels across the entire chromosome. Strong fluctuating balancing selection even induces a loss of genetic variation in unlinked regions, e.g. on different chromosomes. If many loci in the genome are simultaneously under fluctuating balancing selection this could lead to substantial genome-wide reductions in genetic diversity. This may be the case, even if allele-frequency fluctuations are so small that individual footprints are hard to detect. Thus, together with genetic drift, selective sweeps and background selection, fluctuating selection could be one of the major forces shaping levels of genetic diversity in natural populations. Article summaryIn some species with multiple generations per year, many loci in the genome experience strong seasonally fluctuating selection, in some cases with stable maintenance of polymorphism. Here we investigate the consequences for levels of genetic diversity at linked neutral sites. Using analytical approximations and stochastic simulations, we find a characteristic local genetic footprint with a diversity peak around the selected site and a diversity valley further away and a substantial reduction in diversity levels chromosome-wide and even genome-wide.

evolutionary biology↗

bioRxiv2020

The limits to parapatric speciation 3: Evolution of strong reproductive isolation in presence of gene flow despite limited ecological differentiation.

Gene flow tends to impede the accumulation of genetic divergence. Here, we determine the limits for the evolution of postzygotic reproductive isolation in a model of two populations that are connected by gene flow. We consider two selective mechanisms for the creation and maintenance of a genetic barrier: local adaptation leads to divergence among incipient species due to selection against migrants, and Dobzhansky-Muller incompatibilities (DMIs) reinforce the genetic barrier through selection against hybrids. In particular, we are interested in the maximum strength of the barrier under a limited amount of local adaptation, a challenge that may initially face many incipient species. We first confirm that with classical two-locus DMIs, the maximum amount of local adaptation is indeed a limit to the strength of a genetic barrier. However, with three or more loci and cryptic epistasis, this limit holds no longer. In particular, we identify a minimal configuration of three epistatically interacting mutations that is sufficient to confer strong reproductive isolation.

evolutionary biology↗

bioRxiv2019

VolcanoFinder: genomic scans for adaptive introgression

Recent research shows that introgression between closely-related species is an important source of adaptive alleles for a wide range of taxa. Typically, detection of adaptive introgression from genomic data relies on comparative analyses that require sequence data from both the recipient and the donor species. However, in many cases, the donor is unknown or the data is not currently available. Here, we introduce a genome-scan method--VolcanoFinder--to detect recent events of adaptive introgression using polymorphism data from the recipient species only.\n\nVolcanoFinder detects adaptive introgression sweeps from the pattern of excess intermediate-frequency polymorphism they produce in the flanking region of the genome, a pattern which appears as a volcano-shape in pairwise genetic diversity.\n\nUsing coalescent theory, we derive analytical predictions for these patterns. Based on these results, we develop a composite-likelihood test to detect signatures of adaptive introgression relative to the genomic background. Simulation results show that VolcanoFinder has high statistical power to detect these signatures, even for older sweeps and for soft sweeps initiated by multiple migrant haplotypes. Finally, we implement VolcanoFinder to detect archaic introgression in European and sub-Saharan African human populations, and uncovered interesting candidates in both populations, such as TSHR in Europeans and TCHH-RPTN in Africans. We discuss their biological implications and provide guidelines for identifying and circumventing artifactual signals during empirical applications of VolcanoFinder.\n\nAuthor summaryThe process by which beneficial alleles are introduced into a species from a closely-related species is termed adaptive introgression. We present an analytically-tractable model for the effects of adaptive introgression on non-adaptive genetic variation in the genomic region surrounding the beneficial allele. The result we describe is a characteristic volcano-shaped pattern of increased variability that arises around the positively-selected site, and we introduce an open-source method VolcanoFinder to detect this signal in genomic data. Importantly, VolcanoFinder is a population-genetic likelihood-based approach, rather than a comparative-genomic approach, and can therefore probe genomic variation data from a single population for footprints of adaptive introgression, even from a priori unknown and possibly extinct donor species.

evolutionary biology↗

bioRxiv2019

Evolutionary dynamics in structured populations under strong population genetic forces

High rates of migration between subpopulations result in little population differentiation in the long-term neutral equilibrium. However, in the short-term, even very abundant migration may not be enough for subpopulations to equilibrate immediately. In this study, we investigate dynamical patterns of short-term population differentiation in adapting populations via stochastic and analytical modeling through time. We characterize a regime in which selection and migration interact to create non-monotonic patterns of the population differentiation statistic FST when migration is weaker than selection, but stronger than drift. We demonstrate how these patterns can be leveraged to estimate high migration rates that would lead to panmixia in the long term equilibrium using an approximate Bayesian computation approach. We apply this approach to estimate fast migration in a rapidly adapting intra-host Simian-HIV population sampled from different anatomical locations. Notably, we find differences in estimated migration rates between different compartments, all above Nem = 1. This work demonstrates how studying demographic processes on the timescale of selective sweeps illuminates processes too fast to leave signatures on neutral timescales.

evolutionary biology↗

bioRxiv2018

Polygenic Adaptation: From sweeps to subtle frequency shifts

1Evolutionary theory has produced two conflicting paradigms for the adaptation of a polygenic trait. While population genetics views adaptation as a sequence of selective sweeps at single loci underlying the trait, quantitative genetics posits a collective response, where phenotypic adaptation results from subtle allele frequency shifts at many loci. Yet, a synthesis of these views is largely missing and the population genetic factors that favor each scenario are not well understood. Here, we study the architecture of adaptation of a binary polygenic trait (such as resistance) with negative epistasis among the loci of its basis. The genetic structure of this trait allows for a full range of potential architectures of adaptation, ranging from sweeps to small frequency shifts. By combining computer simulations and a newly devised analytical framework based on Yule branching processes, we gain a detailed understanding of the adaptation dynamics for this trait. Our key analytical result is an expression for the joint distribution of mutant alleles at the end of the adaptive phase. This distribution characterizes the polygenic pattern of adaptation at the underlying genotype when phenotypic adaptation has been accomplished. We find that a single compound parameter, the population-scaled background mutation rate {Theta}bg, explains the main differences among these patterns. For a focal locus, {Theta}bg measures the mutation rate at all redundant loci in its genetic background that offer alternative ways for adaptation. For adaptation starting from mutation-selection-drift balance, we observe different patterns in three parameter regions. Adaptation proceeds by sweeps for small {Theta}bg [prsim] 0.1, while small polygenic allele frequency shifts require large {Theta}bg [scsim] 100. In the large intermediate regime, we observe a heterogeneous pattern of partial sweeps at several interacting loci. 2 Author summaryIt is still an open question how complex traits adapt to new selection pressures. While population genetics champions the search for selective sweeps, quantitative genetics proclaims adaptation via small concerted frequency shifts. To date the empirical evidence of clear sweep signals is more scarce than expected, while subtle shifts remain notoriously hard to detect. In the current study we develop a theoretical framework to predict the expected adaptive architecture of a simple polygenic trait, depending on parameters such as mutation rate, effective population size, size of the trait basis, and the available genetic variability at the onset of selection. For a population in mutation-selection-drift balance we find that adaptation proceeds via complete or partial sweeps for a large set of parameter values. We predict adaptation by small frequency shifts for two main cases. First, for traits with a large mutational target size and high levels of genetic redundancy among loci, and second if the starting frequencies of mutant alleles are more homogeneous than expected in mutation-selection-drift equilibrium, e.g. due to population structure or balancing selection.

evolutionary biology↗

bioRxiv2018

The influence of fluctuating population densities on evolutionary dynamics

The causes and consequences of fluctuating population densities are an important topic in ecological literature. Yet, the effects of such fluctuations on maintenance of variation in spatially structured populations have received little analytic treatment. We analyze what happens when two habitats coupled by migration not only differ in their trade-offs in selection but also in their demographic stability - and show that equilibrium allele frequencies can change significantly due to ecological feedback arising from locally fluctuating population sizes. When an ecological niche exhibits such fluctuations, these drive an asymmetry in the relative impact of gene flow, and therefore, the equilibrium frequency of the locally adapted type decreases. Our results extend the classic conditions on maintenance of diversity under selection and migration by including the effect of fluctuating population densities. We find simple analytic conditions in terms of the strength of selection, immigration, and the extent of fluctuations between generations in a continent-island model. Whereas weak fluctuations hardly affect coexistence, strong recurrent fluctuations lead to extinction of the type better adapted to the fluctuating niche - even if the invader is locally maladapted. There is a disadvantage to specialization to an unstable habitat, as it makes the population vulnerable to swamping from more stable habitats.

evolutionary biology↗

bioRxiv2018

Spatial soft sweeps: patterns of adaptation in populations with long-range dispersal

Adaptation in extended populations often occurs through multiple independent mutations responding in parallel to a common selection pressure. As the mutations spread concurrently through the population, they leave behind characteristic patterns of polymorphism near selected loci--so-called soft sweeps--which remain visible after adaptation is complete. These patterns are well-understood in two limits of the spreading dynamics of beneficial mutations: the panmictic case with complete absence of spatial structure, and spreading via short-ranged or diffusive dispersal events, which tessellates space into distinct compact regions each descended from a unique mutation. However, spreading behaviour in most natural populations is not exclusively panmictic or diffusive, but incorporates both short-range and long-range dispersal events. Here, we characterize the spatial patterns of soft sweeps driven by dispersal events whose jump distances are broadly distributed, using lattice-based simulations and scaling arguments. We find that mutant clones adopt a distinctive structure consisting of compact cores surrounded by fragmented \"haloes\" which mingle with haloes from other clones. As long-range dispersal becomes more prominent, the progression from diffusive to panmictic behaviour is marked by two transitions separating regimes with differing relative sizes of halo to core. We analyze the implications of the core-halo structure for the statistics of soft sweep detection in small genomic samples from the population, and find opposing effects of long-range dispersal on the expected diversity in global samples compared to local samples from geographic subregions of the range. We also discuss consequences of the standing genetic variation induced by the soft sweep on future adaptation and mixing.

evolutionary biology↗

bioRxiv2018

The Limits to Parapatric Speciation II: Strengthening a Preexisting Genetic Barrier to Gene Flow in Parapatry

Parapatric speciation has recently received a lot of attention. By encompassing the whole continuum between allopatric and sympatric scenarios, it includes many potential scenarios for the evolution of new species. Building upon previous work, we investigate how a genetic barrier to gene flow, that relies on a single postzygotic genetic incompatibility, may further evolve. We consider a continent island model with three loci involved in pairwise Dobzhansky-Muller incompatibilities (DMIs). Using a deterministic and analytic approach, we derive the conditions for invasion of a new mutation and its consequences on an already existing genetic barrier to gene flow. We focus on quantifying the impact of the epistasis generated by the new mutation on the genetic barrier. We show that the accumulation of genetic incompatibilities in the presence of gene flow is a complex process, where new mutations can either strengthen or destroy a preexisting barrier. In particular, preexisting polymorphism and incompatibilities do not always facilitate the growth of the genetic barrier by accumulation of further barrier genes. Migration may disrupt the snowball effect (the accelerating rate of DMI accumulation in allopatry) because incompatibilities are directly tested by selection. Our results also show an ambiguous role of gene flow, which can either impede or facilitate the strengthening of the genetic barrier. Overall, our results illustrate how the inclusion of gene flow renders the building of a genetic barrier difficult to analyze.

genetics↗

bioRxiv2017

Soft sweeps and beyond: Understanding the patterns and probabilities of selection footprints under rapid adaptation

O_LIThe tempo and mode of adaptive evolution determine how natural selection shapes patterns of genetic diversity in DNA polymorphism data. While slow mutation-limited adaptation leads to classical footprints of \"hard\" selective sweeps, these patterns are different when adaptation responds quickly to a novel selection pressure, acting either on standing genetic variation or on recurrent new mutation. In the past decade, corresponding footprints of \"soft\" selective sweeps have been described both in theoretical models and in empirical data.\nC_LIO_LIHere, we summarize the key theoretical concepts and contrast model predictions with observed patterns in Drosophila, humans, and microbes.\nC_LIO_LIEvidence in all cases shows that \"soft\" patterns of rapid adaptation are frequent. However, theory and data also point to a role of complex adaptive histories in rapid evolution.\nC_LIO_LIWhile existing theory allows for important implications on the tempo and mode of the adaptive process, complex footprints observed in data are, as yet, insufficiently covered by models. They call for in-depth empirical study and further model development.\nC_LI

evolutionary biology↗

bioRxiv2017

Bounds to Parapatric Speciation: A Dobzhansky-Muller incompatibility model involving autosomes, X chromosomes and mitochondria

We investigate the conditions for the origin and maintenance of postzygotic isolation barriers, so called (Bateson-)Dobzhansky-Muller incompatibilities or DMIs, among populations that are connected by gene flow. Specifically, we compare the relative stability of pairwise DMIs among autosomes, X chromosomes, and mitochondrial genes. In an analytical approach based on a continent-island framework, we determine how the maximum permissible migration rates depend on the genomic architecture of the DMI, on sex bias in migration rates, and on sex-dependence of allelic and epistatic effects, such as dosage compensation. Our results show that X-linkage of DMIs can enlarge the migration bounds relative to autosomal DMIs or autosome-mitochondrial DMIs, in particular in the presence of dosage compensation. The effect is further strengthened with male-biased migration. This mechanism might contribute to a higher density of DMIs on the X chromosome (large X-effect) that has been observed in several species clades. Furthermore, our results agree with empirical findings of higher introgression rates of autosomal compared to X-linked loci.

evolutionary biology↗