Egor Lappo

All Publications

• Beneficial reversal of dominance maintains a large-effect resistance polymorphism under fluctuating insecticide selection. Nature ecology & evolution Karageorgi, M., Lyulina, A. S., Bitter, M. C., Lappo, E., Greenblum, S. I., Mouza, Z. K., Tran, C. T., Huynh, A. V., Oken, H., Schmidt, P., Petrov, D. A. 2025

  Abstract

  Large-effect standing genetic variation is commonly found in natural populations and must be maintained in the face of directional natural selection. Theory suggests that under fluctuating selective pressures, beneficial reversal of dominance-where alleles are dominant when beneficial and recessive when deleterious-can strongly stabilize large-effect polymorphisms. However, empirical evidence for this mechanism remains limited because testing requires measurements of selection and dominance in fitness in natural conditions. Here we investigate large-effect fitness polymorphisms at the Ace locus of Drosophila melanogaster that confer insecticide resistance and persist at intermediate frequencies worldwide. By combining laboratory and large-scale field mesocosm experiments with insecticide manipulation and mathematical modelling, we show that the benefits of the resistant Ace alleles are dominant in pesticide-rich environments, while their fitness costs are recessive in pesticide-free environments. We further show that temporally fluctuating insecticide selection generates chromosome-scale genomic perturbations at sites linked to the resistant Ace alleles. Overall, our results suggest that beneficial reversal of dominance under temporally fluctuating selection might plausibly contribute to the maintenance of functional genetic variation and, by stabilizing large frequency fluctuations, impact long-range patterns of genomic variation.

  View details for DOI 10.1038/s41559-025-02853-x

  View details for PubMedID 40954284

  View details for PubMedCentralID 4222749

• Coalescent theory of the ψ directionality index. G3 (Bethesda, Md.) Lappo, E., Rosenberg, N. A. 2025

  Abstract

  The ψ directionality index was introduced by Peter & Slatkin (Evolution 67: 3274-3289, 2013) to infer the direction of range expansions from single-nucleotide polymorphism variation. Computed from the joint site frequency spectrum for two populations, ψ uses shared genetic variants to measure the difference in the amount of genetic drift experienced by the populations, associating excess drift with greater distance from the origin of the range expansion. Although ψ has been successfully applied in natural populations, its statistical properties have not been well understood. In this paper, we define Ψ as a random variable originating from a coalescent process in a two-population demography. For samples consisting of a pair of diploid genomes, one from each of two populations, we derive expressions for moments E[Ψk] for standard parameterizations of bottlenecks during a founder event. For the expectation E[Ψ], we identify parameter combinations that represent distinct demographic scenarios yet yield the same value of E[Ψ]. We also show that the variance V[Ψ] increases with the time since the bottleneck and bottleneck severity, but does not depend on the size of the ancestral population; the ancestral population size affects ψ computed from many biallelic loci only through its contribution to the total number of loci available for the computation. Finally, we analyze the values of E[Ψ] computed from existing demographic models of Drosophila melanogaster and compare them with empirically computed ψ. Our work builds the foundation for theoretical treatments of the ψ index and can help in evaluating its behavior in empirical applications.

  View details for DOI 10.1093/g3journal/jkaf202

  View details for PubMedID 40919609

• Coalescent theory of the ψ directionality index. bioRxiv : the preprint server for biology Lappo, E., Rosenberg, N. A. 2025

  Abstract

  The ψ directionality index was introduced by Peter & Slatkin (Evolution 67: 3274-3289, 2013) to infer the direction of range expansions from single-nucleotide polymorphism variation. Computed from the joint site frequency spectrum for two populations, ψ uses shared genetic variants to measure the difference in the amount of genetic drift experienced by the populations, associating excess drift with greater distance from the origin of the range expansion. Although ψ has been successfully applied in natural populations, its statistical properties have not been well understood. In this paper, we define Ψ as a random variable originating from a coalescent process in a two-population demography. For samples consisting of a pair of diploid genomes, one from each of two populations, we derive expressions for moments E [ Ψ k ] for standard parameterizations of bottlenecks during a founder event. For the expectation E [ Ψ ] , we identify parameter combinations that represent distinct demographic scenarios yet yield the same value of E [ Ψ ] . We also show that the variance V [ Ψ ] increases with the time since the bottleneck, bottleneck severity, and size of the ancestral population. For a sample containing many SNPs, the central limit theorem allows us to approximate the distribution of the observed value of the ψ index conditional on the demographic history. Finally, we analyze the values of E [ Ψ ] computed from existing demographic models of Drosophila melanogaster and compare them with empirically computed ψ . Our work builds the foundation for theoretical treatments of the ψ index and can help in evaluating its behavior in empirical applications.

  View details for DOI 10.1101/2025.06.18.660412

  View details for PubMedID 40667259

  View details for PubMedCentralID PMC12262451

• Dominance reversal maintains large-effect resistance polymorphism in temporally varying environments. bioRxiv : the preprint server for biology Karageorgi, M., Lyulina, A. S., Bitter, M. C., Lappo, E., Greenblum, S. I., Mouza, Z. K., Tran, C. T., Huynh, A. V., Oken, H., Schmidt, P., Petrov, D. A. 2025

  Abstract

  A central challenge in evolutionary biology is to uncover mechanisms maintaining functional genetic variation1. Theory suggests that dominance reversal, whereby alleles subject to fluctuating selection are dominant when beneficial and recessive when deleterious, can help stabilize large-effect functional variation in temporally varying environments2,3. However, empirical evidence for dominance reversal is scarce because testing requires both knowing the genetic architecture of relevant traits and measuring the dominance effects on fitness in natural conditions4. Here, we show that large-effect, insecticide-resistance alleles at the Ace locus in Drosophila melanogaster5,6 persist worldwide at intermediate frequencies and exhibit dominance reversal in fitness as a function of the presence of an organophosphate insecticide. Specifically, we use laboratory assays to show that the resistance benefits driven by these alleles are dominant, while the associated costs are recessive (or codominant). Further, by tracking insecticide resistance and genome-wide allele frequencies in field mesocosms, we find that resistance and resistant alleles increase and then decrease rapidly in response to an insecticide pulse but are maintained at low frequencies in the absence of pesticides. We argue that this pattern is only consistent with beneficial reversal of dominance. We use Wright's theory of dominance7 to hypothesize that dominance reversal should be common in general if the environmental shifts that make alleles deleterious also make them behave effectively as loss-of-function and thus recessive alleles . We also use the known haplotype structure of mesocosm populations to establish that the insecticide pulse generates chromosome-scale genomic perturbations of allele frequencies at linked sites. Overall, our results provide compelling evidence that this mechanism can maintain functional genetic variation and enable rapid adaptation to environmental shifts that can impact patterns of genomic variation at genome-wide scales via linked fluctuating selection.

  View details for DOI 10.1101/2024.10.23.619953

  View details for PubMedID 39554016

• Continuously fluctuating selection reveals fine granularity of adaptation. Nature Bitter, M. C., Berardi, S., Oken, H., Huynh, A., Lappo, E., Schmidt, P., Petrov, D. A. 2024

  Abstract

  Temporally fluctuating environmental conditions are a ubiquitous feature of natural habitats. Yet, how finely natural populations adaptively track fluctuating selection pressures via shifts in standing genetic variation is unknown1,2. Here we generated genome-wide allele frequency data every 1-2 generations from a genetically diverse population of Drosophila melanogaster in extensively replicated field mesocosms from late June to mid-December (a period of approximately 12 total generations). Adaptation throughout the fundamental ecological phases of population expansion, peak density and collapse was underpinned by extremely rapid, parallel changes in genomic variation across replicates. Yet, the dominant direction of selection fluctuated repeatedly, even within each of these ecological phases. Comparing patterns of change in allele frequency to an independent dataset procured from the same experimental system demonstrated that the targets of selection are predictable across years. In concert, our results reveal a fitness relevance of standing variation that is likely to be masked by inference approaches based on static population sampling or insufficiently resolved time-series data. We propose that such fine-scaled, temporally fluctuating selection may be an important force contributing to the maintenance of functional genetic variation in natural populations and an important stochastic force impacting genome-wide patterns of diversity at linked neutral sites, akin to genetic draft.

  View details for DOI 10.1038/s41586-024-07834-x

  View details for PubMedID 39143223

  View details for PubMedCentralID 8385344

• Solving the Arizona search problem by imputation. iScience Lappo, E., Rosenberg, N. A. 2024; 27 (2): 108831

  Abstract

  An "Arizona search" is an evaluation of the numbers of pairs of profiles in a forensic-genetic database that possess partial or complete genotypic matches; such a search assists in establishing the extent to which a set of loci provides unique identifications. In forensic genetics, however, the potential for performing Arizona searches is constrained by the limited availability of actual forensic profiles for research purposes. Here, we use genotype imputation to circumvent this problem. From a database of genomes, we impute genotypes of forensic short-tandem-repeat (STR) loci from neighboring single-nucleotide polymorphisms (SNPs), searching for partial STR matches using the imputed profiles. We compare the distributions of the numbers of partial matches in imputed and actual profiles, finding close agreement. Despite limited potential for performing Arizona searches with actual forensic STR profiles, the questions that such searches seek to answer can be posed with imputation-based Arizona searches in increasingly large SNP databases.

  View details for DOI 10.1016/j.isci.2024.108831

  View details for PubMedID 38323008

• A lattice structure for ancestral configurations arising from the relationship between gene trees and species trees. Discrete applied mathematics (Amsterdam, Netherlands : 1988) Lappo, E., Rosenberg, N. A. 2024; 343: 65-81

  Abstract

  To a given gene tree topology G and species tree topology S with leaves labeled bijectively from a fixed set X, one can associate a set of ancestral configurations, each of which encodes a set of gene lineages that can be found at a given node of the species tree. We introduce a lattice structure on ancestral configurations, studying the directed graphs that provide graphical representations of lattices of ancestral configurations. For a matching gene tree topology and species tree topology G=S, we present a method for defining the digraph of ancestral configurations from the tree topology by using iterated cartesian products of graphs. We show that a specific set of paths on the digraph of ancestral configurations is in bijection with the set of labeled histories - a well-known phylogenetic object that enumerates possible temporal orderings of the coalescences of a tree. For each of a series of tree families, we obtain closed-form expressions for the number of labeled histories by using this bijection to count paths on associated digraphs. Finally, we prove that our lattice construction extends to nonmatching tree pairs, and we use it to characterize pairs (G,S) having the maximal number of ancestral configurations for a fixed G. We discuss how the construction provides new methods for performing enumerations of combinatorial aspects of gene and species trees.

  View details for DOI 10.1016/j.dam.2023.09.033

  View details for PubMedID 38078045

  View details for PubMedCentralID PMC10704929

• Cultural transmission of move choice in chess. Proceedings. Biological sciences Lappo, E., Rosenberg, N. A., Feldman, M. W. 2023; 290 (2011): 20231634

  Abstract

  The study of cultural evolution benefits from detailed analysis of cultural transmission in specific human domains. Chess provides a platform for understanding the transmission of knowledge due to its active community of players, precise behaviours and long-term records of high-quality data. In this paper, we perform an analysis of chess in the context of cultural evolution, describing multiple cultural factors that affect move choice. We then build a population-level statistical model of move choice in chess, based on the Dirichlet-multinomial likelihood, to analyse cultural transmission over decades of recorded games played by leading players. For moves made in specific positions, we evaluate the relative effects of frequency-dependent bias, success bias and prestige bias on the dynamics of move frequencies. We observe that negative frequency-dependent bias plays a role in the dynamics of certain moves, and that other moves are compatible with transmission under prestige bias or success bias. These apparent biases may reflect recent changes, namely the introduction of computer chess engines and online tournament broadcasts. Our analysis of chess provides insights into broader questions concerning how social learning biases affect cultural evolution.

  View details for DOI 10.1098/rspb.2023.1634

  View details for PubMedID 37964528

• Concordance of spatial graphs CANADIAN MATHEMATICAL BULLETIN-BULLETIN CANADIEN DE MATHEMATIQUES Lappo, E. 2023; 66 (4): 1091-1108

  View details for DOI 10.4153/S000843952300019X

  View details for Web of Science ID 000964361900001

• Conformity and anti-conformity in a finite population. Journal of theoretical biology Lappo, E., Denton, K. K., Feldman, M. W. 2023: 111429

  Abstract

  Conformist and anti-conformist cultural transmission have been studied both empirically, in several species, and theoretically, with population genetic models. Building upon standard, infinite-population models (IPMs) of conformity, we introduce finite-population models (FPMs) and study them via simulation and a diffusion approximation. In previous IPMs of conformity, offspring observe the variants of n adult role models, where n is often three. Numerical simulations show that while the short-term behavior of the FPM with n=3 role models is well approximated by the IPM, stable polymorphic equilibria of the IPM become effective equilibria of the FPM at which the variation persists prior to fixation or loss, and which produce plateaus in curves for fixation probabilities and expected times to absorption. In the FPM with n=5 role models, the population may switch between two effective equilibria, which is not possible in the IPM, or may cycle between frequencies that are not effective equilibria, which is possible in the IPM. In all observed cases of 'equilibrium switching' and 'cycling' in the FPM, model parameters exceed O(1/N), required for the diffusion approximation, resulting in an over-estimation of the actual times to absorption. However, in those cases with n=5 role models that have one effective equilibrium and stable fixation states, even if conformity coefficients exceed O(1/N), the diffusion approximation matches closely the numerical simulations of the FPM. This suggests that the robustness of the diffusion approximation depends not only on the magnitudes of coefficients, but also on the qualitative behavior of the conformity model.

  View details for DOI 10.1016/j.jtbi.2023.111429

  View details for PubMedID 36746297

• Approximations to the expectations and variances of ratios of tree properties under the coalescent. G3 (Bethesda, Md.) Lappo, E., Rosenberg, N. A. 2022

  Abstract

  Properties of gene genealogies such as tree height (H), total branch length (L), total lengths of external (E) and internal (I) branches, mean length of basal branches (B), and the underlying coalescence times (T) can be used to study population-genetic processes and to develop statistical tests of population-genetic models. Uses of tree features in statistical tests often rely on predictions that depend on pairwise relationships among such features. For genealogies under the coalescent, we provide exact expressions for Taylor approximations to expected values and variances of ratios Xn/Yn, for all 15 pairs among the variables {Hn, Ln, En, In, Bn, Tk}, considering n leaves and 2 ≤ k ≤ n. For expected values of the ratios, the approximations match closely with empirical simulation-based values. The approximations to the variances are not as accurate, but they generally match simulations in their trends as n increases. Although En has expectation 2 and Hn has expectation 2 in the limit as n → ∞, the approximation to the limiting expectation for En/Hn is not 1, instead equaling π2/3-2 ≈ 1.28987. The new approximations augment fundamental results in coalescent theory on the shapes of genealogical trees.

  View details for DOI 10.1093/g3journal/jkac205

  View details for PubMedID 35951748

• A compendium of covariances and correlation coefficients of coalescent tree properties. Theoretical population biology Alimpiev, E., Rosenberg, N. A. 2021

  Abstract

  Gene genealogies are frequently studied by measuring properties such as their height ( H), length (L), sum of external branches (E), sum of internal branches (I), and mean of their two basal branches (B), and the coalescence times that contribute to the other genealogical features (T). These tree properties and their relationships can provide insight into the effects of population-genetic processes on genealogies and genetic sequences. Here, under the coalescent model, we study the 15 correlations among pairs of features of genealogical trees: Hn, Ln, En, In, Bn, and Tk for a sample of size n, with 2≤k≤n. We report high correlations among Hn, Ln, In, and Bn, with all pairwise correlations of these quantities having values greater than or equal to 6[6zeta(3)+6-pi2]/(pi18+9pi2-pi4)0.84930 in the limit as n, where zeta is the Riemann zeta function. Although En has expectation 2 for all n and Hn has expectation 2 in the n limit, their limiting correlation is 0. The results contribute toward understanding features of the shapes of coalescent trees.

  View details for DOI 10.1016/j.tpb.2021.09.008

  View details for PubMedID 34757022

• Enumeration of coalescent histories for caterpillar species trees and p-pseudocaterpillar gene trees. Advances in applied mathematics Alimpiev, E., Rosenberg, N. A. 2021; 131

  Abstract

  For a fixed set X containing n taxon labels, an ordered pair consisting of a gene tree topology G and a species tree topology S bijectively labeled with the labels of X possesses a set of coalescent histories-mappings from the set of internal nodes of G to the set of edges of S describing possible lists of edges in S on which the coalescences in G take place. Enumerations of coalescent histories for gene trees and species trees have produced suggestive results regarding the pairs (G, S) that, for a fixed n, have the largest number of coalescent histories. We define a class of 2-cherry binary tree topologies that we term p-pseudocaterpillars, examining coalescent histories for non-matching pairs (G, S) in the case in which S has a caterpillar shape and G has a p-pseudocaterpillar shape. Using a construction that associates coalescent histories for (G, S) with a class of "roadblocked" monotonic paths, we identify the p-pseudocaterpillar labeled gene tree topology that, for a fixed caterpillar labeled species tree topology, gives rise to the largest number of coalescent histories. The shape that maximizes the number of coalescent histories places the "second" cherry of the p-pseudocaterpillar equidistantly from the root of the "first" cherry and from the tree root. A symmetry in the numbers of coalescent histories for p-pseudocaterpillar gene trees and caterpillar species trees is seen to exist around the maximizing value of the parameter p. The results provide insight into the factors that influence the number of coalescent histories possible for a given gene tree and species tree.

  View details for DOI 10.1016/j.aam.2021.102265

  View details for PubMedID 34483422