About
We're an evolutionary theory and population genetics group in the Department of Ecology & Evolution at the University of Chicago, working on a diverse range of topics including: introgression and speciation, selfish genetic elements, the evolution of recombination, and the impact of selection and demography on the genetic architecture of complex traits.
Research topics
- Genetics
- Biology
- Evolutionary biology
- Statistics
- Sociology
- Demography
- Geography
- Agronomy
- Ecology
- Computational biology
Selected publications
PLoS Genetics · 2026-03-09 · 1 citations
articleOpen accessSenior authorStabilizing selection on a polygenic trait reduces the trait's genetic variance by (i) generating correlations (linkage disequilibria) between opposite-effect alleles throughout the genome, and (ii) selecting against rare alleles at loci that affect the trait, eroding heterozygosity at these loci. Here, we show that the linkage disequilibria, which stabilizing selection generates on a rapid timescale, slow down the subsequent allele-frequency dynamics at individual loci, which proceed on a much longer timescale. Exploiting this separation of timescales, we obtain expressions for the expected per-generation change in minor-allele frequency at individual loci, as functions of the effect sizes at these loci, the strength of selection on the trait, its variance and heritability, and the linkage relations among loci. Using whole-genome simulations, we show that our expressions predict allele-frequency dynamics under stabilizing selection more accurately than the formulae that have previously been used for this purpose. Our results have implications for understanding the genetic architecture of complex traits.
Open MIND · 2026-02-09
dataset1st authorCorrespondingStabilizing selection on a polygenic trait reduces the trait's genetic variance by (i) generating correlations (linkage disequilibria) between opposite-effect alleles throughout the genome, and (ii) selecting against rare alleles at loci that affect the trait, eroding heterozygosity at these loci. Here, we show that the linkage disequilibria, which stabilizing selection generates on a rapid timescale, slow down the subsequent allele-frequency dynamics at individual loci, which proceed on a much longer timescale. Exploiting this separation of timescales, we obtain expressions for the expected per-generation change in minor-allele frequency at individual loci, as functions of the effect sizes at these loci, the strength of selection on the trait, its variance and heritability, and the linkage relations among loci. Using whole-genome simulations, we show that our expressions predict allele-frequency dynamics under stabilizing selection more accurately than the formulae that have previously been used for this purpose. Our results have implications for understanding the genetic architecture of complex traits.
Proceedings of the National Academy of Sciences · 2026-03-20 · 1 citations
articleOpen access1st authorCorrespondingWe consider a biological system composed of multiple genetically variable components, the combined result of which is a quantitative trait under stabilizing selection for an optimal value. We show mathematically that, while the mean value of the system is ultimately constrained to remain near its optimum, the mean contributions of individual components are free to drift far from their initial values. Each component's drift, though qualitatively identical to neutral drift, is slower by a factor that depends on the fraction of the system's genetic variance contributed by the component. We further show that symmetric mutation between alleles that increase and decrease components' contributions to the system imposes a weak long-term brake on components' drift. Our results provide a population-genetic basis for "system drift," the concept that individual components of a biological system can evolve despite selective constraint on their combined product. A special case is a single polygenic trait under stabilizing selection, where our results predict that the mean contributions to the trait of different subregions of the genome, such as the chromosomes, can drift despite constraint on the genome-wide value. To indicate the broad applicability of our results, we explore their implications for the evolution of gene expression, selection against interspecific hybrids, selection against turnovers of sex-determining systems, and the division of labor in mutualisms.
Sexually antagonistic environments and the stability of environmental sex determination
bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-10
articleOpen accessAbstract Just as sexually antagonistic genetic variants have different effects on male and female fitness, environmental conditions too can have sexually antagonistic fitness effects. Such ‘Charnov–Bull effects’ have been invoked to explain the origin and persistence of environmental sex determination (ESD), which allows development of each sex in the environments in which it has a comparative advantage. Here, we study different forms of Charnov–Bull effects to characterize how they shape the evolution and stability of ESD. We show that the precise functional form of Charnov–Bull effects can generate large differences in the vulnerability of ESD systems to the invasion of sex-biasing alleles, as well as in the fate of those alleles if they invade. For some configurations of Charnov–Bull effects, strong sex-biasing alleles are likely to spread to intermediate frequencies, rather than to fixation, resulting in ‘mixed’ ESD systems in which large genetic effects segregate. Overall, our results indicate that the precise nature of Charnov–Bull effects can play a crucial role in the evolutionary dynamics of ESD.
bioRxiv (Cold Spring Harbor Laboratory) · 2025-09-20 · 3 citations
preprintOpen access1st authorCorrespondingAbstract We consider a biological system composed of multiple genetically variable components, the combined result of which is a quantitative trait under stabilizing selection for an optimal value. We show mathematically that, while the mean value of the system is ultimately constrained to remain near its optimum, the values of individual components are free to drift far from their initial values. Each component’s drift, though qualitatively similar to neutral drift, is slower by a factor that depends on the fraction of the system’s genetic variance contributed by the component. Our results provide a population-genetic basis for ‘system drift’, the concept that individual components of a biological system can evolve despite selective constraint on their combined product. A special case is a single polygenic trait under stabilizing selection, where our results predict that the mean genetic contributions to the trait of different subregions of the genome, such as the chromosomes, can drift despite constraint on the genome-wide genetic value. We explore the implications of this latter result for selection against interspecific hybrids and selection against turnovers of sex-determining systems. We further apply our general results to a continuous public goods game played between two species, where they predict that individual species’ contributions to a costly public good can drift freely. Finally, we show that symmetric mutation between alleles that increase and decrease components’ contributions to the system provides a weak long-term brake on components’ drift.
PLoS Biology · 2024 · 65 citations
1st authorCorresponding- Biology
- Genetics
- Evolutionary biology
A central aim of genome-wide association studies (GWASs) is to estimate direct genetic effects: the causal effects on an individual's phenotype of the alleles that they carry. However, estimates of direct effects can be subject to genetic and environmental confounding and can also absorb the "indirect" genetic effects of relatives' genotypes. Recently, an important development in controlling for these confounds has been the use of within-family GWASs, which, because of the randomness of mendelian segregation within pedigrees, are often interpreted as producing unbiased estimates of direct effects. Here, we present a general theoretical analysis of the influence of confounding in standard population-based and within-family GWASs. We show that, contrary to common interpretation, family-based estimates of direct effects can be biased by genetic confounding. In humans, such biases will often be small per-locus, but can be compounded when effect-size estimates are used in polygenic scores (PGSs). We illustrate the influence of genetic confounding on population- and family-based estimates of direct effects using models of assortative mating, population stratification, and stabilizing selection on GWAS traits. We further show how family-based estimates of indirect genetic effects, based on comparisons of parentally transmitted and untransmitted alleles, can suffer substantial genetic confounding. We conclude that, while family-based studies have placed GWAS estimation on a more rigorous footing, they carry subtle issues of interpretation that arise from confounding.
Causal interpretations of family GWAS in the presence of heterogeneous effects
Proceedings of the National Academy of Sciences · 2024-09-13 · 17 citations
articleOpen access1st authorCorrespondingFamily-based genome-wide association studies (GWASs) are often claimed to provide an unbiased estimate of the average causal effects (or average treatment effects; ATEs) of alleles, on the basis of an analogy between the random transmission of alleles from parents to children and a randomized controlled trial. We show that this claim does not hold in general. Because Mendelian segregation only randomizes alleles among children of heterozygotes, the effects of alleles in the children of homozygotes are not observable. This feature will matter if an allele has different average effects in the children of homozygotes and heterozygotes, as can arise in the presence of gene-by-environment interactions, gene-by-gene interactions, or differences in linkage disequilibrium patterns. At a single locus, family-based GWAS can be thought of as providing an unbiased estimate of the average effect in the children of heterozygotes (i.e., a local average treatment effect; LATE). This interpretation does not extend to polygenic scores (PGSs), however, because different sets of SNPs are heterozygous in each family. Therefore, other than under specific conditions, the within-family regression slope of a PGS cannot be assumed to provide an unbiased estimate of the LATE for any subset or weighted average of families. In practice, the potential biases of a family-based GWAS are likely smaller than those that can arise from confounding in a standard, population-based GWAS, and so family studies remain important for the dissection of genetic contributions to phenotypic variation. Nonetheless, their causal interpretation is less straightforward than has been widely appreciated.
bioRxiv (Cold Spring Harbor Laboratory) · 2024-06-28 · 13 citations
preprintOpen accessSenior authorCorrespondingAbstract Stabilizing selection on a polygenic trait reduces the trait’s genetic variance by (i) generating correlations (linkage disequilibria) between opposite-effect alleles throughout the genome, and (ii) selecting against rare alleles at loci that affect the trait, eroding heterozygosity at these loci. Here, we show that the linkage disequilibria, which stabilizing selection generates on a rapid timescale, slow down the subsequent allele-frequency dynamics at individual loci, which proceed on a much longer timescale. Exploiting this separation of timescales, we obtain expressions for the expected per-generation change in minor-allele frequency at individual loci, as functions of the effect sizes at these loci, the strength of selection on the trait, its variance and heritability, and the linkage relations among loci. Using whole-genome simulations, we show that our expressions predict allele-frequency dynamics under stabilizing selection more accurately than the formulae that have previously been used for this purpose. Our results have implications for understanding the genetic architecture of complex traits.
Stabilizing selection generates selection against introgressed DNA
bioRxiv (Cold Spring Harbor Laboratory) · 2024-08-20 · 8 citations
preprintOpen access1st authorCorrespondingAbstract DNA introgressed from one population into another is often deleterious to the recipient population if the two populations have diverged genetically from one another. Previous explanations of this phenomenon have posited negative interactions between donor-population alleles and the recipient population’s genome or environment, or higher genetic load in the donor population. Here, we show that stabilizing selection on quantitative traits—even around the same optimal trait values in the two populations and when the populations are demographically identical—generates selection against the minor-parent ancestry in a population formed via unequal admixture of the two populations. We calculate the rate at which minor-parent ancestry is purged under this mechanism, both in the early generations after admixture and in the long term, and we verify these calculations with whole-genome simulations. Because of its ubiquity, stabilizing selection offers a general mechanism for the deleterious effect of introgressed ancestry.
Two teosintes made modern maize
Science · 2023 · 146 citations
- Sociology
- Biology
- Geography
in the highlands of Mexico some 4000 years after domestication began. We show that variation in admixture is a key component of maize diversity, both at individual loci and for additive genetic variation underlying agronomic traits. Our results clarify the origin of modern maize and raise new questions about the anthropogenic mechanisms underlying dispersal throughout the Americas.
Frequent coauthors
- 33 shared
Martin A. Nowak
Harvard University
- 20 shared
Benjamin Allen
Emmanuel College - Massachusetts
- 20 shared
Pavitra Muralidhar
- 13 shared
Jason Olejarz
Harvard University
- 8 shared
George W. A. Constable
University of York
- 6 shared
David Haig
Harvard University
- 6 shared
Graham Coop
University of California, Davis
- 6 shared
Ning Yang
Ministry of Education of the People's Republic of China
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