Deleterious Mutation/Epimutation-Selection Balance with and without Inbreeding: A Population (Epi)Genetics Model.

Epigenetics in the form of DNA methylation and other processes is an established property of genotypes and a focus of empirical research. Yet, there remain fundamental gaps in the evolutionary theory of epigenetics. To support a comprehensive understanding of epigenetics, this paper investigates theoretically the combined effects of deleterious mutation and epimutation with and without inbreeding. Both spontaneous epimutation and paramutation are considered to cover a broader range of epigenetic phenomena. We find that inbreeding generally reduces the amount of segregating deleterious genetic and epigenetic variation at equilibrium, although interestingly inbreeding can also increase the amount of deleterious genetic or epigenetic variation. Furthermore, we also demonstrate that epimutation indirectly can cause increased or decreased deleterious genetic variation at equilibrium relative to classic expectations, which is particularly evident when paramutation is occurring. With the addition of deleterious epimutation, there may be significantly increased purging of deleterious variation in more inbred populations and a significantly increased amount of segregating deleterious variation in more outbred populations, with notable exceptions.

A Measure of the DNA Barcode Gap for Applied and Basic Research.

DNA barcoding has largely established itself as a mainstay for rapid molecular taxonomic identification in both academic and applied research. The use of DNA barcoding as a molecular identification method depends on a "DNA barcode gap"-the separation between the maximum within-species difference and the minimum between-species difference. Previous work indicates the presence of a gap hinges on sampling effort for focal taxa and their close relatives. Furthermore, both theory and empirical work indicate a gap may not occur for related pairs of biological species. Here, we present a novel evaluation approach in the form of an easily calculated set of nonparametric metrics to quantify the extent of proportional overlap in inter- and intraspecific distributions of pairwise differences among target species and their conspecifics. The metrics are based on a simple count of the number of overlapping records for a species falling within the bounds of maximum intraspecific distance and minimum interspecific distance. Our approach takes advantage of the asymmetric directionality inherent in pairwise genetic distance distributions, which has not been previously done in the DNA barcoding literature. We apply the metrics to the predatory diving beetle genus Agabus as a case study because this group poses significant identification challenges due to its morphological uniformity despite both relative sampling ease and well-established taxonomy. Results herein show that target species and their nearest neighbor species were found to be tightly clustered and therefore difficult to distinguish. Such findings demonstrate that DNA barcoding can fail to fully resolve species in certain cases. Moving forward, we suggest the implementation of the proposed metrics be integrated into a common framework to be reported in any study that uses DNA barcoding for identification. In so doing, the importance of the DNA barcode gap and its components for the success of DNA-based identification using DNA barcodes can be better appreciated.

Spatial structure and benefits to hosts allow plasmids with and without post-segregational killing systems to coexist.

To persist, a plasmid relies on being passed on to a daughter cell, but this does not always occur. Plasmids with post-segregational killing (PSK) systems kill a daughter cell if the plasmid has not been passed on. By killing the host, it also kills competing plasmids in the same host, something competing plasmids without a similar system cannot do. Accordingly, plasmids with PSK systems can displace other plasmids. In nature, plasmids with and without PSK systems coexist and prior theory has suggested this is expected to be very rare or unstable, such that one or the other type of plasmid eventually takes over. Here, we show that if there is spatial structure and plasmids confer benefits to hosts, coexistence of plasmids occurs broadly. Often plasmids confer benefits (even ones with a PSK system) and bacteria are often spatially structured. So, our results may be generally applicable.

Meiosis at three loci in autotetraploids: Probabilities of gamete modes and genotypes without and with preferential cross-over formation.

A long-standing goal in the field of polyploid biology has been the derivation of mathematical models of gamete mode formation. These models form the basis of statistical inference and evolutionary theory. Here, we present 3-locus models of gamete mode formation in autotetraploids without and with preferential cross-over formation. The three loci are assumed to occur on one arm of the same chromosome. For preferential cross-over formation, one of the three loci affects the tendency for sets of sister chromatids to pair and therefore affects rates of recombination. The models are derived such that the process of double reduction is a function of rates of synaptic partner switches and recombination, as opposed to being independent of these processes. We assume potentially one synaptic partner switch per meiosis. We also assume the coefficient of coincidence is one, such that cross-over events are independent, given a set of cross-over rates. Illustrative cases are examined demonstrating differences in the gamete mode probabilities without and with preferential cross-over formation. Lastly, we explore the accuracy of maximum likelihood estimates of the probability of synaptic partner switches and preferential cross-over formation when the locus controlling preference is at a proximal, middle, or distal location on the chromosome arm. All Supplementary Information is available at https://github.com/ckgriswold/3-locus-autotetraploid-meiosis .

A dynamic ancestral graph model and GPU-based simulation of a community based on metagenomic sampling.

In this paper, we present an ancestral graph model of the evolution of a guild in an ecological community. The model is based on a metagenomic sampling design in that a random sample is taken at the community, as opposed the taxon, level and species are discovered by genetic sequencing. The specific implementation of the model envisions an ecological guild that was founded by colonization at some point in the past that then potentially undergoes diversification by natural selection. Within the graph, species emerge and evolve through the diversification process and their densities in the graph are dynamic and governed by both ecological drift and random genetic drift, as well as differential viability. We employ the 3% sequence divergence rule at a marker locus to identify operational taxonomic units. We then explore approaches to see whether there are indirect signals of the diversification process, including population genetic and ecological approaches. In terms of population genetics, we study the joint site frequency spectrum of OTUs, as well its associated statistics. In terms of ecology, we study the species (or OTU) abundance distribution. For both, we observe deviations from neutrality, which indicates that there may be signals of diversifying selection in metagenomic studies under certain conditions. The model is available as a GPU-based computer program in C/C++ and using OpenCL, with the long-term goal of adding functionality iteratively to model large-scale eco-evolutionary processes for metagenomic data.

The effects of migration load, selfing, inbreeding depression, and the genetics of adaptation on autotetraploid versus diploid establishment in peripheral habitats.

The distribution and abundance of polyploids has intrigued biologists since their discovery in the early 20th century. A pattern in nature that may give insight to processes that shape the distribution and abundance of polyploids is that polyploid populations are sometimes associated with peripheral habitats within the range of a species of mixed ploidy. Here, adaptation and competition of a diploid versus an autotetraploid population in a peripheral habitat are examined theoretically. It is shown that a nascent autotetraploid population adapts to and outcompetes a diploid population in the periphery when the rate of gamete dispersal is high, and when the mode of gene action is recessive for moderate to high rates of selfing. With additive or dominant modes of gene action, the conditions for an autotetraploid to outcompete a diploid in the periphery appear determined more by the rate of selfing and less by gamete dispersal. All of these results are based on empirical work that suggests inbreeding depression is higher in diploids versus autotetraploids. Generally, the results indicate that, although autotetraploids incur minority cytotype exclusion, diploids face burdens themselves. In the case of adaptation to a peripheral habitat, this burden is migration load from gamete and propagule dispersal.

Two-Locus Local Adaptation by Additive or Epistatic Gene Combinations in Autotetraploids Versus Diploids.

In this article, we present a theoretical comparison of local adaptation between diploid and autotetraploid populations when fitness is determined by either additive or epistatic interactions between alleles at 2 loci. A continent-island model of local adaptation is derived, with 1-way migration from the continent to the island and distinct genotypes adaptive on the continent versus the island. The meiotic component of the model accounts for multivalent formation and the processes of chromosomal gametic disequilibrium and double reduction, which are unique to autotetraploids. Both the adaptability and efficiency of adaptation are investigated, where adaptability asks whether a population adapts and efficiency is the rate of adaptation. With an additive genetic basis to fitness, diploids experience better adaptability and efficiency than autotetraploids. With epistasis, our results indicate a limited parameter space in which autotetraploids have greater adaptability than diploids, but results indicate an interesting difference between adaptability and efficiency of adaptation. Oftentimes, diploids exhibit greater adaptability whereas autotetraploids exhibit greater efficiency of adaptation. These findings provide evidence for the advantage of epistasis within autotetraploids when efficiency of adaptation is of interest. Although autotetraploids are more efficient, under the same conditions and at equilibrium, diploid populations often have higher mean local fitness. Overall, the most ideal situation for autotetraploid local adaptation compared to diploids is when epistasis is strong, mutation is weak, recombination is high, selection is strong, deleterious selection is additive, chromosomal gametic disequilibrium is present, and double reduction is absent.

Properties of Samples With Segregating Polymerase Chain Reaction (PCR) Dropout Mutations Within a Species.

In polymerase chain reaction (PCR)-based DNA sequencing studies, there is the possibility that mutations at the binding sites of primers result in no primer binding and therefore no amplification. In this article, we call such mutations PCR dropouts and present a coalescent-based theory of the distribution of segregating PCR dropout mutations within a species. We show that dropout mutations typically occur along branch sections that are at or near the base of a coalescent tree, if at all. Given that a dropout mutation occurs along a branch section near the base of a tree, there is a good chance that it causes the alleles of a large fraction of a species to go unamplified, which distorts the tree shape. Expected coalescence times and distributions of pairwise sequence differences in the presence of PCR dropout mutations are derived under the assumptions of both neutrality and background selection. These expectations differ from when PCR dropout mutations are absent and may form the basis of inferential approaches to detect the presence of dropout mutations, as well as the development of unbiased estimators of statistics associated with population-level genetic variation.

An ancestral process with selection in an ecological community.

An ecological community is a geographical area composed of two or more species. The ancestral histories of individuals from the same and different species in an ecological community may be interconnected due to direct and indirect interactions. Here, we present a model of the ancestral history of an ecological community that is built upon the framework of coalescent and ancestral graph theory. The model includes selection, whereby the fitness of an ancestral lineage is a function of both its abiotic environment and interactions with individuals from its biotic environment. The model also allows for metacommunity structure. We first define a forward-time percolation process characterizing the evolution of an ecological community and then present its corresponding backward-time graphical model in the limit of large population sizes. Next, we present expectations of properties of phenotypes in the graph. These expectations give insight into the structure of phenotypic variation and trait-environment covariances across local communities, including the effects of drift, intra and inter-species genealogical structure and the sampling effects of selection. In addition, we derive expectations for multivariate phenotypic diversity in a community assuming neutrality and compare this to expectations with stabilizing selection.

A fitness trade-off between seasons causes multigenerational cycles in phenotype and population size.

Although seasonality is widespread and can cause fluctuations in the intensity and direction of natural selection, we have little information about the consequences of seasonal fitness trade-offs for population dynamics. Here we exposed populations of Drosophila melanogaster to repeated seasonal changes in resources across 58 generations and used experimental and mathematical approaches to investigate how viability selection on body size in the non-breeding season could affect demography. We show that opposing seasonal episodes of natural selection on body size interacted with both direct and delayed density dependence to cause populations to undergo predictable multigenerational density cycles. Our results provide evidence that seasonality can set the conditions for life-history trade-offs and density dependence, which can, in turn, interact to cause multigenerational population cycles.

Additive genetic variation and evolvability of a multivariate trait can be increased by epistatic gene action.

Epistatic gene action occurs when mutations or alleles interact to produce a phenotype. Theoretically and empirically it is of interest to know whether gene interactions can facilitate the evolution of diversity. In this paper, we explore how epistatic gene action affects the additive genetic component or heritable component of multivariate trait variation, as well as how epistatic gene action affects the evolvability of multivariate traits. The analysis involves a sexually reproducing and recombining population. Our results indicate that under stabilizing selection conditions a population with a mixed additive and epistatic genetic architecture can have greater multivariate additive genetic variation and evolvability than a population with a purely additive genetic architecture. That greater multivariate additive genetic variation can occur with epistasis is in contrast to previous theory that indicated univariate additive genetic variation is decreased with epistasis under stabilizing selection conditions. In a multivariate setting, epistasis leads to less relative covariance among individuals in their genotypic, as well as their breeding values, which facilitates the maintenance of additive genetic variation and increases a population׳s evolvability. Our analysis involves linking the combinatorial nature of epistatic genetic effects to the ancestral graph structure of a population to provide insight into the consequences of epistasis on multivariate trait variation and evolution.

Epistasis can accelerate adaptive diversification in haploid asexual populations.

A fundamental goal of the biological sciences is to determine processes that facilitate the evolution of diversity. These processes can be separated into ecological, physiological, developmental and genetic. An ecological process that facilitates diversification is frequency-dependent selection caused by competition. Models of frequency-dependent adaptive diversification have generally assumed a genetic basis of phenotype that is non-epistatic. Here, we present a model that indicates diversification is accelerated by an epistatic basis of phenotype in combination with a competition model that invokes frequency-dependent selection. Our model makes use of a genealogical model of epistasis and insights into the effects of balancing selection on the genealogical structure of a population to understand how epistasis can facilitate diversification. The finding that epistasis facilitates diversification may be informative with respect to empirical results that indicate an epistatic basis of phenotype in experimental bacterial populations that experienced adaptive diversification.

Body size, carry-over effects and survival in a seasonal environment: consequences for population dynamics.

In seasonal populations, vital rates are not only determined by the direct effects of density at the beginning of each season, but also by density at the beginning of past seasons. Such delayed density dependence can arise via non-lethal effects on individuals that carry over to influence per capita rates. In this study, we examine (i) whether parental breeding density influences offspring size, (ii) how this could carry over to affect offspring survival during the subsequent non-breeding period and (iii) the population consequences of this relationship. Using Drosophila melanogaster, the common fruit fly, submitted to distinct breeding and non-breeding seasons, we first used a controlled laboratory experiment to show that high parental breeding density leads to small offspring size, which then affects offspring survival during the non-breeding period but only at high non-breeding densities. We then show that a model with the interaction between parental breeding density and offspring density at the beginning of the non-breeding season best explained offspring survival over 36 replicated generations. Finally, we developed a biseasonal model to show that the positive relationship between parental density and offspring survival can dampen fluctuations in population size between breeding and non-breeding seasons. These results highlight how variation in parental density can lead to differences in offspring quality which result in important non-lethal effects that carry over to influence per capita rates the following season, and demonstrate how this phenomenon can have important implications for the long-term dynamics of seasonal populations.

Evidence for selection on gene expression in cultivated rice (Oryza sativa).

Artificial selection has been used throughout plant domestication and breeding to develop crops that are adapted to diverse environments. Here, we investigate whether gene regulatory changes have been widespread targets of lineage-specific selection in cultivated lines Minghui 63 and Zhenshan 97 of rice, Oryza sativa. A line experiencing positive selection for either an increase or a decrease in genes' transcript abundances is expected to have an overabundance of expression quantitative trait locus (eQTL) alleles that increase or decrease those genes' expression, respectively. Results indicate that several genes that share Gene Ontology terms or are members of the same coexpression module have eQTL alleles from one parent that consistently increase gene expression relative to the second parent. A second line of evidence for lineage-specific selection is an overabundance of cis-trans pairs of eQTL alleles that affect gene expression in the same direction (are reinforcing). Across all cis-trans pairs of eQTL, including pairs that both weakly and strongly affect gene expression, there is no evidence for selection. However, the frequency of genes with reinforcing eQTL increases with eQTL strength. Therefore, there is evidence that eQTL with strong effects were positively selected during rice cultivation. Among 41 cis-trans pairs with strong trans eQTL, 31 have reinforcing eQTL. Several of the candidate genes under positive selection accurately predict phenotypic differences between Minghui 63 and Zhenshan 97. Overall, our results suggest that positive selection for regulatory alleles may be a key factor in plant improvement.

A comparative study indicates both positive and purifying selection within ryanodine receptor (RyR) genes, as well as correlated evolution.

Ryanodine receptors are Ca(2+) ion channels that allow Ca(2+) to flow into the cytosol, from an internal store, in the form of transients. RyRs form a small gene family and vertebrates have three major isoforms, RyR1, RyR2, and RyR3, which are mixed and matched in different combinations in different tissues resulting in different Ca(2+) transients for each tissue. In this study, we characterized the interspecies evolution of RyRs within vertebrates. First, we compared the nucleotide divergence of key gene regions including divergent regions (DRs), which are believed to be responsible for the functional divergence between RyRs, and mutation hot-spot regions, which are responsible for RyR-related pathologies. We found evidence that DRs undergo positive selection and mutation hot-spot regions undergo purifying selection. Second, we estimated the extent of purifying selection for RyR1, RyR2, and RyR3 by estimating dN/dS ratios. We found all three genes to be under strong purifying selection, overall. This is consistent with RyRs being used in a diverse set of physiological contexts and therefore under potentially high pleiotropic constraint. Third, we tested for the correlated evolution of dN/dS ratios between RyR genes. We found that RyR2 and RyR3, and RyR3 and a skeletal form of dihydropyridine receptor (DHPR) have correlated rates of evolution. We propose that compensatory effects may explain their correlated evolution. We tested for compensatory function by simulating mutations via a physiological model of RyR function, but did not find evidence for compensation, which indicates that the correlation is likely a result of another process.

Density-mediated carry-over effects explain variation in breeding output across time in a seasonal population.

In seasonal environments, where density dependence can operate throughout the annual cycle, vital rates are typically considered to be a function of the number of individuals at the beginning of each season. However, variation in density in the previous season could also cause surviving individuals to be in poor physiological condition, which could carry over to influence individual success in the following season. We examine this hypothesis using replicated populations of Drosophila melanogaster, the common fruitfly, over 23 non-overlapping generations with distinct breeding and non-breeding seasons. We found that the density at the beginning of the non-breeding season negatively affected the fresh weight of individuals that survived the non-breeding season and resulted in a 25% decrease in per capita breeding output among those that survived to the next season to breed. At the population level, per capita breeding output was best explained by a model that incorporated density at the beginning of the previous non-breeding season (carry-over effect, COE) and density at the beginning of the breeding season. Our results support the idea that density-mediated COEs are critical for understanding population dynamics in seasonal environments.

Carry-over effects, sequential density dependence and the dynamics of populations in a seasonal environment.

Most animal populations have distinct breeding and non-breeding periods, yet the implications of seasonality on population dynamics are not well understood. Here, we introduce an experimental model system to study the population dynamics of two important consequences of seasonality: sequential density dependence and carry-over effects (COEs). Using a replicated seasonal population of Drosophila, we placed individuals at four densities in the non-breeding season and then, among those that survived, placed them to breed at three different densities. We show that COEs arising from variation in non-breeding density negatively impacts individual performance by reducing per capita breeding output by 29-77%, implying that non-lethal COEs can have a strong influence on population abundance. We then parametrized a bi-seasonal population model from the experimental results, and show that both sequential density dependence and COEs can stabilize long-term population dynamics and that COEs can reduce population size at low intrinsic rates of growth. Our results have important implications for predicting the successful colonization of new habitats, and for understanding the long-term persistence of seasonal populations in a wide range of taxa, including migratory organisms.

Epistasis can increase multivariate trait diversity in haploid non-recombining populations.

We evaluate the effect of epistasis on genetically-based multivariate trait variation in haploid non-recombining populations. In a univariate setting, past work has shown that epistasis reduces genetic variance (additive plus epistatic) in a population experiencing stabilizing selection. Here we show that in a multivariate setting, epistasis also reduces total genetic variation across the entire multivariate trait in a population experiencing stabilizing selection. But, we also show that the pattern of variation across the multivariate trait can be more even when epistasis occurs compared to when epistasis is absent, such that some character combinations will have more genetic variance when epistasis occurs compared to when epistasis is absent. In fact, a measure of generalized multivariate trait variation can be increased by epistasis under weak to moderate stabilizing selection conditions, as well as neutral conditions. Likewise, a measure of conditional evolvability can be increased by epistasis under weak to moderate stabilizing selection and neutral conditions. We investigate the nature of epistasis assuming a multivariate-normal model genetic effects and investigate the nature of epistasis underlying the biophysical properties of RNA. Increased multivariate diversity occurs for populations that are infinite in size, as well as populations that are finite in size. Our model of finite populations is explicitly genealogical and we link our findings about the evenness of eigenvalues with epistasis to prior work on the genealogical mapping of epistatic effects.

The mapping of epistatic effects onto a genealogical tree in haploid populations.

In this paper we present a model that maps epistatic effects onto a genealogical tree for a haploid population. Prior work has demonstrated that genealogical structure causes the genotypic values of individuals to covary. Our results indicate that epistasis can reduce genotypic covariance that is caused by genealogical structure. Genotypic effects (both additive and epistatic) occur along the branches of a genealogical tree, from the base of the tree to its tips. Epistasis reduces genotypic covariance because there is a reweighting of the contribution of branches to the states of genotypes compared to the additive case. Branches near the tips of a genealogical tree contribute proportionally more genetic effects with epistasis than without epistasis. Epistatic effects are most numerous at basal positions in a genealogical tree when a population is constant in size and experiencing no selection, optimizing selection, diversifying selection or directional selection, indicating that epistatic effects are typically old. For a population that is growing in size, epistatic effects are most numerous at midpoints in a genealogical tree, indicating epistatic effects are of moderate age. Our results are important in that they suggest epistatic effects may typically explain deep (old) divergences and broad patterns of divergence that exist in populations, except in growing populations. In a growing population, epistatic effects may cause more within group divergence higher up in a tree and less between group divergence that is deep in a tree. The distribution of the number of epistatic effects and the expected variance and covariance in the number of epistatic effects is also provided assuming neutrality.