Kimberly Julie Gilbert

The relationship between dominance and selection coefficients is a long-debated topic in evolutionary genetics and important for understanding evolutionary dynamics of populations. How it evolved and how it may vary across species or populations is not fully understood. Using simulations, we investigate how purifying selection and genetic drift affect the distribution of dominance coefficients for segregating deleterious variants. We find that large populations express h–s relationships shaped by efficient selection against highly deleterious and additive mutations, resulting in excess weakly deleterious and recessive mutations. This matches the classic inverse relationship between selection and dominance. Genetic drift in small populations, however, results in a wider range of dominance coefficients for any segregating deleterious variant and reduces or removes the h–s relationship. By investigating allele fixation, we reveal a nuanced dependency on the strength of selection across different simulated selection and dominance distributions. We also compare the combined impact of genetic drift and repeated founder events in simulated range expansions and how these impact the segregating distribution of h, employing differences in effective population size between species core and edge. While dominance patterns in core populations resemble large, constant-size populations, edge populations lack recessive mutations relative to small, constant-size populations. Our findings emphasize the importance of genetic drift and purifying selection in shaping the observed negative relationship between dominance and selection coefficients in large populations. Small populations, however, show an h–s relationship closer to de novo mutations, without the effect of purifying selection. Therefore, it is important to consider population size, genetic drift, and the underlying distribution of dominance coefficients when studying the evolutionary dynamics of deleterious mutations.

Ancestral genomes are essential for studying the diversification of life from the last universal common ancestor to modern organisms. Methods have been proposed to infer ancestral gene order, but they lack scalability, limiting the depth to which gene neighborhood evolution can be traced back. We introduce edgeHOG, a tool designed for accurate ancestral gene order inference with linear time complexity. Validated on various benchmarks, edgeHOG was applied to the entire OMA orthology database, encompassing 2,845 extant genomes across all domains of life. This represents the first tree-of-life scale inference, resulting in 1,133 ancestral genomes. In particular, we reconstructed ancestral contigs for the last common ancestor of eukaryotes, dating back around 1.8 billion years, and observed significant functional association among neighboring genes. The method also dates gene adjacencies, revealing conserved histone clusters and rapid sex chromosome rearrangements, enabling computational inference of these features.

Runs of homozygosity (ROHs) are indicative of elevated homozygosity and inbreeding due to mating of closely related individuals. Self-fertilization can be a major source of inbreeding which elevates genome-wide homozygosity and thus should also create long ROHs. While ROHs are frequently used to understand inbreeding in the context of conservation and selective breeding, as well as for consanguinity of populations and their demographic history, it remains unclear how ROH characteristics are altered by selfing and if this confounds expected signatures of inbreeding due to demographic change. Using simulations, we study the impact of the mode of reproduction and demographic history on ROHs. We apply random forests to identify unique characteristics of ROHs, indicative of different sources of inbreeding. We pinpoint distinct features of ROHs that can be used to better characterize the type of inbreeding the population was subjected to and to predict outcrossing rates and complex demographic histories. Using additional simulations and four empirical datasets, two from highly selfing species and two from mixed-maters, we predict the selfing rate and validate our estimations. We find that self-fertilization rates are successfully identified even with complex demography. Population genetic summary statistics improve algorithm accuracy particularly in the presence of additional inbreeding, e.g. from population bottlenecks. Our findings highlight the importance of ROHs in disentangling confounding factors related to various sources of inbreeding and demonstrate situations where such sources cannot be differentiated. Additionally, our random forest models provide a novel tool to the community for inferring selfing rates using genomic data.

Runs of homozygosity (ROHs) are indicative of elevated homozygosity and inbreeding due to mating of closely related individuals. Self-fertilization can be a major source of inbreeding which elevates genomewide homozygosity and thus should also create long ROHs. While ROHs are frequently used to understand inbreeding in the context of conservation and selective breeding, as well as for consanguinity of populations and their demographic history, it remains unclear how ROH characteristics are altered by selfing and if this confounds expected signatures of inbreeding due to demographic change. Using simulations, we study the impact of the mode of reproduction and demographic history on ROHs. We apply random forests to identify unique characteristics of ROHs, indicative of different sources of inbreeding. We pinpoint distinct features of ROHs that can be used to better characterize the type of inbreeding the population was subjected to and to predict outcrossing rates and complex demographic histories. Using additional simulations and four empirical datasets, two from highly selfing species and two from mixedmaters, we predict the selfing rate and validate our estimations. We find that self-fertilization rates are successfully identified even with complex demography. Population genetic summary statistics improve algorithm accuracy particularly in the presence of additional inbreeding, e.g., from population bottlenecks. Our findings highlight the importance of ROHs in disentangling confounding factors related to various sources of inbreeding and demonstrate situations where such sources cannot be differentiated. Additionally, our random forest models provide a novel tool to the community for inferring selfing rates using genomic data.

Inversions are structural mutations that reverse the sequence of a chromosome segment and reduce the effective rate of recombination in the heterozygous state. They play a major role in adaptation, as well as in other evolutionary processes such as speciation. Although inversions have been studied since the 1920s, they remain difficult to investigate because the reduced recombination conferred by them strengthens the effects of drift and hitchhiking, which in turn can obscure signatures of selection. Nonetheless, numerous inversions have been found to be under selection. Given recent advances in population genetic theory and empirical study, here we review how different mechanisms of selection affect the evolution of inversions. A key difference between inversions and other mutations, such as single nucleotide variants, is that the fitness of an inversion may be affected by a larger number of frequently interacting processes. This considerably complicates the analysis of the causes underlying the evolution of inversions. We discuss the extent to which these mechanisms can be disentangled, and by which approach.AbstractInversions often play key roles in adaptation and speciation, but the processes that direct their evolution are obscured by the characteristic that makes them so unique (reduced recombination between arrangements). In this review, we examine how different mechanisms can impact inversion evolution, weaving together both theoretical and empirical studies. We emphasize that most patterns are overdetermined (i.e. can be caused by multiple processes), but we highlight new technologies that provide a path forward towards disentangling these mechanisms.

As species expand their geographic ranges, colonizing populations face novel ecological conditions, such as new environments and limited mates, and suffer from evolutionary consequences of demographic change through bottlenecks and mutation load accumulation. Self-fertilization is often observed at species range edges and, in addition to countering the lack of mates, is hypothesized as an evolutionary advantage against load accumulation through increased homozygosity and purging. We study how selfing impacts the accumulation of genetic load during range expansion via purging and/or speed of colonization. Using simulations, we disentangle inbreeding effects due to demography versus due to selfing and find that selfers expand faster, but still accumulate load, regardless of mating system. The severity of variants contributing to this load, however, differs across mating system: higher selfing rates purge large-effect recessive variants leaving a burden of smaller-effect alleles. We compare these predictions to the mixed-mating plant Arabis alpina, using whole-genome sequences from refugial outcrossing populations versus expanded selfing populations. Empirical results indicate accumulation of expansion load along with evidence of purging in selfing populations, concordant with our simulations, suggesting that while purging is a benefit of selfing evolving during range expansions, it is not sufficient to prevent load accumulation due to range expansion.

Species range expansions are a common demographic history presenting populations with multiple evolutionary challenges. It is not yet fully understood if self-fertilization, which is often observed at species range edges, may create an evolutionary advantage against these challenges. Selfing provides reproductive reassurance to counter Allee effects and selfing may purge accumulated mutational burden due to founder events (expansion load) by further increasing homozygosity. We study how selfing impacts the accumulation of genetic load during range expansion via purging and/or speed of colonization. Using simulations, we disentangle inbreeding effects due to demography versus due to selfing and find that selfers expand faster, but still accumulate load, regardless of mating system. The severity of variants contributing to this load, however, differs across mating system: higher selfing rates purge large-effect recessive variants leaving a burden of smaller-effect alleles. We compare these predictions to the mixedmating plant Arabis alpina , using whole-genome sequences from refugial outcrossing populations versus expanded selfing populations. Empirical results indicate accumulation of expansion load along with evidence of purging in selfing populations, concordant with our simulations, and suggesting that while purging is a benefit of selfing evolving during range expansions, it is not sufficient to prevent load accumulation due to range expansion. Author Summary: The geographic space that species occupy, i.e. the species range, is known to fluctuate over time due to changing environmental conditions. Since the most recent glaciation, many species have recolonized available habitat as the ice sheets melted, expanding their range. When populations at species range margins expand into newly available space, they suffer from an accumulation of deleterious alleles due to repeated founder effects. We study whether self-fertilization, which is considered an evolutionary deadend, can be favored under these expanding edge conditions. Selfing has two important effects: allowing for faster expansion due to reproductive assurance and purging recessive deleterious alleles by exposing them to selection as homozygotes. We use simulations to identify the impact of selfing on expanded populations and then compare these results to an empirical dataset to assess whether our predictions are met. We use the mixed-mating plant alpine rock-cress ( Arabis alpina ) since it has both expanded since the last glaciation and undergone a mating shift to selfing. We find that selfing does not prevent the accumulation of deleterious load, however purging does still act to remove the most severe variants, indicating that selfing provides this benefit during range expansions.

Chromosomal inversions are often thought to facilitate local adaptation and population divergence because they can link multiple adaptive alleles into non‐recombining genomic blocks. Selection should thus be more efficient in driving inversion‐linked adaptive alleles to high frequency in a population, particularly in the face of maladaptive gene flow. But what if ecological conditions and hence selection on inversion‐linked alleles change? Reduced recombination within inversions could then constrain the formation of optimal combinations of pre‐existing alleles under these new ecological conditions. Here, we outline this idea of inversions limiting adaptation and divergence when ecological conditions change across time or space. We reason and use simulations to illustrate that the benefit of inversions for local adaptation and divergence under one set of ecological conditions can come with a concomitant constraint for adaptation to novel sets of ecological conditions. This limitation of inversions to adaptation may contribute to the maintenance of polymorphism within species.

Chromosomal inversions are often thought to facilitate local adaptation and population divergence because they can link multiple adaptive alleles into non-recombining genomic blocks. Selection should thus be more efficient in driving inversion-linked adaptive alleles to high frequency in a population, particularly in the face of maladaptive gene flow. But, what if ecological conditions and hence selection on inversion-linked alleles change? Reduced recombination within inversions could then constrain the formation of optimal combinations of pre-existing alleles under these new ecological conditions. Here, we outline this idea of inversions limiting adaptation and divergence when ecological conditions change across time or space. We reason that the benefit of inversions for local adaptation and divergence under one set of ecological conditions can come with a concomitant constraint for adaptation to novel sets of ecological conditions. This limitation of inversions to adaptation may also provide one possible explanation for why inversions are often maintained as polymorphisms within species.