Sarah Otto

For organisms to genetically adapt, they need to have or acquire mutations that affect their survival and reproductive success. The effects of mutations depend not only on the abiotic factors extrinsic to the organism, but also its biotic interactions as well as the intrinsic state of the organism. Preexisting mutations in the genome will either favor or prevent certain adaptive paths. This thesis contributes knowledge of two aspects of life cycle evolution using the budding yeast Saccharomyces cerevisiae. My evolutionary experiment of phenotypic responses to sexual selection showed that the two mating types of yeast, though often considered indistinguishable, respond differently to increased amounts of mating competition. These results have implications for our understanding of mating system evolution. In a bioinformatic project, I found that changes to the molecular function of proteins do not directly correspond to fitness differences among lines with multiple known mutations in the lab. These results affirm that mutations in proteins act on a system of molecular reactions which determine fitness, and caution against assuming a direct relationship between effects on molecular function and fitness. Finally, I conducted an experiment to measure the fitness effects of mutations in haploids versus diploids. The experimental method used to produce the three genotypic states led to large changes in fitness, impeding our investigation. Most notably I observed a large loss in respiratory function among my experimental replicates that correlated strongly with the presence of the wildtype TID1/RDH54 gene. While unable to answer the question originally stated, the experimental lines produced are a valuable resource for investigations into how the nuclear recombination machinery may increase the likelihood of mitochondrial mutations. Together, these results illustrate the utility of laboratory experiments to both answer and pose new evolutionary questions about such fundamental phenomena as the evolution of sex and the fitness effect of mutations.

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A phylogenetic tree captures the evolutionary relationships among sampled taxa – major taxonomic groups, species, infraspecific taxa, or isolates. Phylogenetic analysis is a central component of evolutionary and ecological studies, as it lends a unifying framework to draw inferences about evolutionary and ecological processes that form biodiversity. Via phylogenetic comparative methods, trait data (for example, morphological or physiological data) and geographical data may be analyzed jointly with a given phylogeny to test specific hypotheses about the evolution and ecology of focal groups of organisms. In this thesis dissertation, I present four studies demonstrating how phylogenetic analysis can yield new evolutionary and ecological insights. In the first two studies, I compare the evolutionary fates of polyploid versus diploid lineages in fish and to test whether polyploidization coincides with speciation events in land plants. Polyploid species arise from whole genome duplication and often exhibit morphological, physiological, and ecological differentiation from their diploid parents. Understanding their evolutionary patterns in the background of diploid species help us to understand why polyploidization is abundant in some organisms (plants) but not in others (fishes). In the other two studies, I explore the biodiversity of freshwater red algae in the wild and aquarium shops, using phylogenetic analyses to reveal potential introductions of these organisms via the global aquarium trade. Furthermore, I identify candidate genetic markers that may be more suitable than commonly used markers to facilitate future studies of phylogenetic community ecology of the red algae. Not only do these studies illustrate the utility of phylogenetic analyses to tackle diverse questions in evolution and ecology, but they also have forwarded the discussion on those four distinct topics.

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Coevolution between hosts and their parasites is widespread with important emergent consequences fornatural systems from across the tree of life. The Red Queen Hypothesis suggests coevolution should maintaingenetic variation in hosts and favour the evolution of sexual reproduction. Mathematical models havedemonstrated that coevolutionary dynamics and the resulting effects on genetic variation and evolution ofsex depend fundamentally on the genetic basis and life-history of the host-parasite interaction. Our understandingof the interaction genetics in natural systems is, however, still limited. In Chapter 2 I develop astatistical method based on genome-wide association studies (GWAS) to identify the genetic interactionsbetween hosts and their parasites, demonstrating that inference of these genetic interactions is essential for arobust understanding of epidemiological traits.Classic models, including the one used in Chapter 2, consider the interaction between hosts and theirfree-living pathogens. Many pathogens are, however, directly transmitted between hosts and hence subjectto epidemiological dynamics. In the Chapter 3, I consider the effects of these epidemiological dynamics oncoevolution. We find, that epidemiological dynamics disrupt classic “Red Queen allele frequency cycles”observed in free-living pathogens, a change in dynamics that may limit the ability of coevolution to favourthe evolution of sexual reproduction. Chapters 4 and 5 extend this by exploring the effects of epidemiologicaldynamics on the maintenance of genetic variation. Chapter 4 develops a baseline for the effect, examiningthe stochastic dynamics of heterozyogsity in a free-living pathogen population of constant size. In contrastto existing hypotheses, we find that coevolution in this classic model does not maintain genetic variation.In Chapter 5 we show that epidemiology can maintain genetic variation in hosts of directly transmittedpathogens, due in part to associated changes in population sizes. My thesis, therefore, demonstrates that, likeother aspects of host and pathogen life-history, disease epidemiology fundamentally affects coevolutionarydynamics with implications for the evolution of sexual reproduction and the maintenance of genetic variation. Supplementary materials available at: http://hdl.handle.net/2429/77298.

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Humans are causing rapid changes to the biotic and abiotic conditions on Earth. My thesis investigates how competition might shape adaptation to an altered environment. Intraspecific competition creates diversifying selection, which alters the genetic variation available for adaptation. Using an individual-based model, I found that intraspecific variation altered the genetic variance-covariance matrix by pushing standing genetic variation to more closely resemble available resources. This changed the “genetic line of least resistance” so that standing genetic variation and de novo mutation both provided possibilities for evolutionary rescue in different directions. Competition between species can also influence evolution to abiotic change. Using an individual-based model I found that differences in population size and competitive ability, between two species, could facilitate coexistence and in some cases cause evolution to occur in the opposite direction to that predicted from environmental change. In an empirical setting, I asked whether species diversity may alter adaptation to abiotic change by changing population size, increasing genetic diversity, and/or by altering selection experienced by a focal species. Using a reciprocal transplant experiment on grasses evolved for 14 years under ambient and elevated CO₂ conditions, in communities of low or high species-richness, I found that the biological community altered the nature of selection in elevated CO₂, so that adaptation was observed primarily when species were grown in a community similar to the one in which they were previously selected. Lastly, I tested whether functional traits of species observed today might reflect differences in the nature of selection experienced in different biotic and abiotic environments. In contrast to expectation I only found the main effects of species diversity and abiotic change to influence plant functional traits. Overall, my research highlights an important role for species interactions in altering adaptation to abiotic environmental change, which cannot be overlooked when predicting how species will adapt to climate change.

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One of the most striking features of the natural world is the fit of an organism to its surroundings. Much of this fit, i.e., adaptation, arises from evolution by natural selection. Adaptation is thus often thought to be a sure thing; eventually a beneficial allele will arise and/or increase in frequency, ad infinitum. But sometimes adaptation is more challenging and evolution by natural selection is not a sure thing. This thesis deals with one such type of adaptive challenge, adaptation that requires the prolonged persistence of genotypes that are expected to be declining in number. The first example is fitness-valley crossing, where adaptation is the result of multiple components that are each selected against when alone but are beneficial in combination. Chapter 2 extends the mathematical framework describing such situations to include biased transmission of traits from one generation to the next. The analysis shows that meiotic drive, uniparental inheritance, and cultural inheritance can greatly facilitate peak shifts across a valley of low fitness. Chapters 3-5 deal with a second example, evolutionary rescue, where declining populations are rescued from extinction by rapid adaptation. Two of the mathematical models analyze how species interactions (predation) and alternative selective surfaces (fitness functions), respectively, affect the ability of a focal population to adapt and persist in a gradually changing world. They find that predators can counterintuitively help prey persist (e.g., through an 'evolutionary hydra effect') and that weakening selection (i.e., antagonistic epistasis) can produce unexpected extinctions ('evolutionary tipping points'). The final model explores evolutionary rescue following an abrupt environmental change on a fitness landscape. The analysis shows that rescue can be more likely by two mutations than one and that the number of mutations that rescue takes leaves a signature in the distribution of fitness effects among survivors.

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Evolution proceeds through genetic changes to individuals, which are either propagated or disappear over generations. Adaptation is one of the main mechanisms driving these changes in genetic composition. Speciation can also result from different, and incompatible, genetic changes occurring in different populations. This thesis furthers our knowledge of the genetics of adaptation and speciation using the budding yeast Saccharomyces cerevisiae. My work on the genetic basis of adaptation to high concentrations of copper, when contrasted with a similar experiment using the fungicide nystatin, showed that the environment has a strong influence on both the number of genes that are the targets of selection and the types of potentially beneficial mutations. These results have implications for the repeatability of genetic evolution. In a second study, I found that genetic interactions between individually isolated single-step beneficial mutations from the same selective environment often exhibited the type of epistasis that underlies speciation even though these mutations occurred within a single biosynthetic pathway. These results support the mutation-order model of speciation by adaptation, where the chance order of mutations in separated populations leads to divergence and the build-up of reproductive isolation due to genetic incompatibility. Negative genetic interactions became positive when the level of stress was increased, indicating that genetically-based reproductive isolation can also be environment-dependent. Finally, I found that diploid yeast were generally not able to adapt to a level of fungicide to which haploid yeast can adapt. Diploids have been found to adapt to a lower concentration of the same drug, indicating that the exact environment (type and concentration) and ploidy can have an impact on the likelihood of genetic rescue. Together, these results have implications for our understanding of the genetic basis of adaptation in different types of environments and different levels of the same environmental stressor.

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In this thesis, I investigate several aspects of life cycle evolution using mathematical models. (1) We expect natural selection to favour organisms that reproduce as often and as quickly as possible. However, many species delay development unless particular environments or rare disturbance events occur. I use models to ask when delayed development (e.g., seed dormancy) in long-lived species can be favoured by selection. I find that long-lived plants experience `immaturity risk': the risk of death due to a population-scale disturbance, such as a fire, before reproducing. This risk can be sufficient to favour germination in the disturbance years only. I show how demographic models can be constructed in order to estimate the contribution of this mechanism (and two other mechanisms) to the evolution of dormancy in a particular environment. (2) All sexually reproducing eukaryotes alternate between haploid and diploid phases. However, selection may not occur in both phases to the same extent. I use models to investigate the evolution of the time spent in haploid versus diploid phases. The presence of a homologous gene copy in diploids has important population genetic effects because it can mask the other gene copy from selection. A key innovation of my investigation is to allow haploids and homozygous diploids to have different fitnesses (intrinsic fitness differences). This reveals a novel hypothesis for the evolution of haploid-diploid strategies (where selection occurs in both phases), where the genetic effects of ploidy are balanced against intrinsic fitness differences. (3) Many sex chromosome systems are characterized by a lack of recombination between sex chromosome types. The predominant explanation for this phenomenon involves differences in selection between diploid sexes. I develop a model for the evolution of recombination between the sex chromosomes in which there is a period of selection among haploid genotypes in pollen or sperm. I find that a period of haploid selection can also drive the evolution of suppressed recombination between sex chromosomes, which should become enriched for genes selected in the haploid phase. This model predicts that the tempo of sex chromosome evolution can depend on the degree of competition among haploids.

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We can learn about the factors that promote and constrain speciation by comparing multiple instances of the evolution of reproductive isolation. It is particularly useful to compare systems with similar environmental transitions because natural selection is likely responsible for any evolutionary patterns that are consistently associated with ecological variation. In this thesis, I examine two cases of putatively similar recent or incipient ecological speciation in the sunflower genus Helianthus. In each case, the divergence observed between geographically adjacent populations is associated with adaptation to sand dunes. In my first study, I comprehensively test for reproductive isolation between dune and non-dune ecotypes of H. petiolaris. Despite their recent divergence, I find that multiple reproductive barriers separate them, including post-pollination assortative mating in the form of pollen competition. In addition, I find that a striking difference in seed size between the ecotypes is a consequence of divergent natural selection, and that it leads to strong and extrinsic reproductive isolation via selection against immigrants and hybrids. I then broaden my study to include the dune endemic, H. neglectus, which is sister to typical H. petiolaris. I look for chromosomal rearrangements between H. neglectus and H. petiolaris, and find almost as many large translocations between them as between more distantly related sunflowers. Finally, I discover that larger seeds are associated with dune environments in both systems and that the genetic basis of that phenotypic evolution is partiality repeated. Taken together, these results suggest that dune adaption within H. petiolaris and between H. petiolaris and H. neglectus has similar consequences. However, it remains to be seen whether assortative mating and chromosomal evolution are unique to the evolution of dune H. petiolaris and H. neglectus, respectively. Ultimately, understanding the similarities and differences between these systems will help answer the question - how predictable is speciation?

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I argue that many scientific theories and explanations are irreducibly narrative in character. To this end I propose an account of a generalized narrative, which goes against the widespread view that narratives are by definition particularized. On my account, generalized narratives are sequences of causally connected event-types in the duration of a system, with a beginning, middle and end (whereas particularized narratives are causally connected sequences of event-tokens). Many important scientific theories have a narrative structure that is not reducible to the kinds of formal statements typically identified with theory formulations, i.e., equations and “if-then” conditionals. Similarly, some scientific explanations have a narrative structure that is not reducible to the structure of an “argument” with premises and a conclusion. Narratives, generalized or particularized, play a threefold role in theorizing: heuristic, structural, and explanatory: 1) Through narratives, scientists explore imaginative scenarios where possible causal connections and outcomes are explored before a mathematical or otherwise formal framework is in place; 2) Narratives constitute the core of some theories, and can embed formal elements in them; 3) The causal order of event-types or event-tokens forms the basis of explanations. Throughout, I motivate and illustrate my proposal with examples from evolutionary biology and physics.

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Natural selection acts on phenotypes within populations, yet it is allele frequency changesat the genetic level that enable adaptation. To properly understand the evolutionary processwe thus need to understand how the genotypic and external environments affect beneficialmutations and, in turn, affect the fitness of individuals. In this thesis I used the buddingyeast, Saccharomyces cerevisiae to explore the genotypic basis, phenotypic diversity, and fitnesseffects of beneficial mutations in a variety of genotypic and external environments.I first describe fitness experiments designed to elucidate the factor that alloweddiploid mutants to overtake haploid populations during batch culture evolution. I comparedhaploid and diploid lines isolated at many time points using multiple growth phaseand competitive fitness assays, yet diploids failed to demonstrate an advantage for anymeasure. I then conducted a related set of experiments that compared the rate of adaptationof haploid and diploid populations across seven different environments. I found thatalthough haploid populations adapted faster than diploids in all environments, there wasconsiderable variation between ploidy populations and among environments.Experimental evolution results can be difficult to explain without knowledge of the specificmutations involved. The remainder of this thesis thus focused on a set of 20 uniquebeneficial mutations I acquired that confer tolerance to nystatin, a fungicide. The mutationsare in four different genes that act close together late in the ergosterol biosynthesispathway. Although the genetic basis of adaptation was narrow, lines that carried mutationsin different genes were not equally tolerant to nystatin and were found to exhibit differentgene-by-environment interactions. Surprisingly, the mutations had a larger effect size innystatin in a haploid background than in a homozygous diploid background. I then showthat the dominance of these mutations (i.e., the degree to which mutations in a heterozygotebehave like wildtype) was not constant between environments. Heterozygotes grewstochastically under nystatin stress, and resequencing uncovered rapid and pervasive lossof heterozygosity. Combined, this work demonstrates that both ploidy and the environmentcan have a large influence on the effect of beneficial mutations and illustrates theoften-dynamic nature of evolution.

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In this thesis I develop several models examining how geneticevolution can affect evolutionary processes at a broader scale.First, I ask how evolution would proceed at a locus that governs themutation rate between alleles mediating interactions between hosts andparasites. By relaxing several simplifying assumptions I am able toexplore the affects of sex and recombination. I find that, when themodifier locus is completely linked, the mutation rate evolves towardthe optimum rate. With looser linkage, however, lower mutation ratesevolved. This work can potentially explain the high rates of antigenicswitching observed in many asexual taxa.Second, I investigate how ploidy levels and the genetic modelunderlying species interactions affect how evolution proceeds from afree-living to a parasitic life-history. I find that the transitionto parasitism occurs over a broader range of parameters when theparasite is haploid. The role of host ploidy is more complicated,depending on the model governing host-parasite interactions. Theseresults provide a first characterization of how genetic architectureaffects selection on life-history in antagonistic speciesinteractions.Third, I develop a model of sexual selection in an environment withspatial variation in the carrying capacity, but no variation inresource type. I show that, when searching for a mate is costly, thisvariation can stabilize demographic fluctuations, facilitatinglong-term coexistence of species differing only in sexual traits.This is the first study to demonstrate the existence of conditionsunder which sexual selection alone can promote the long-termcoexistence of ecologically equivalent species in sympatry.Finally, I develop a model characterizing the effects of matingpreferences on species interactions in hybrid zones. I find that thespatial distribution of genotypes observed in many "mosaic" hybridzones might be better explained by species-specific differences inmating than by differences in ecology (the common explanation). Inaddition, I develop a statistical method that can be applied toempirical hybrid zone data to estimate how "mosaic" the hybrid zoneis. I test this statistic on data from the Mytilus edulis and M. galloprovincialis hybrid zone.

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Species selection - heritable trait-dependent differences in rates of speciation or extinction - may be responsible for variation in both taxonomic and trait diversity among clades. While initially controversial, interest in species selection has been revived by the accumulation of evidence of widespread trait-dependent diversification. In my thesis, I developed and applied a number of new likelihood-based methods for investigating species selection by detecting the association between species traits and speciation or extinction rates. These methods are explicitly phylogenetic and incorporate simple, but commonly used, models of speciation, extinction, and trait evolution; I assume throughout that speciation and extinction can be modelled as a birth-death process where rates depend in some way on one or more traits, and that these traits evolve under a Markov process. In particular, I extended the BiSSE (Binary State Speciation and Extinction) method to allow use with incompletely resolved phylogenies, and developed analogous methods for multi-state discrete traits or combinations of binary traits (MuSSE; Multi-State Speciation and Extinction) and quantitative traits (QuaSSE; Quantitative State Speciation and Extinction). I tested the statistical performance of the methods using simulations, investigating their performance with variation in tree size, degree of resolution, number of traits, and departure from the true model. I used each method to consider a different biological question; I found that sexual dimorphism was shortlived but associated with elevated rates of speciation in shorebirds; that solitariness and monogamy are associated with decreased speciation rates in primates (showing that a previous analysis was robust to treating both traits simultaneously); and that body size was a poor predictor of speciation rates in primates. In chapter 5, I extended this analysis of body size to all mammals, and investigated if within-lineage increases in body size (Cope's rule) were balanced by species selection against large bodied species. I found little support for this hypothesis, with clade-specific differences in the direction of species selection and idiosyncratic variation in speciation rates. Together, the methods I have developed allow testing of long-standing hypotheses about causes of variation in biological diversity.

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In this thesis I explore several topics related to the evolution of plant reproductive characters.First, I consider mating system evolution at a single locus that simultaneously affects multiple fitness components, including pollen export, selfing rate, and viability (i.e., survival or a similar change in male and female function). I use two approaches. First, I assume frequency-independent mating, so the model characterizes prior selfing (Chapter 2). Second, I assume that selfing rates are determined by a "mass action" process, which characterizes several additional modes of selfing (Chapter 3). For both approaches, pleiotropy between increased viability and selfing rate reduces opportunities for the evolution of pure outcrossing, can favor complete selfing despite high inbreeding depression, and notably, can cause the evolution of mixed mating despite very high inbreeding depression. These results suggest that selection by non-pollinating agents may help explain mixed mating, particularly in species with very high inbreeding depression.Second, I analyze the potential for different genome regions to harbor intra-locus sexually-antagonistic polymorphism. Such polymorphism, involving one allele that benefits fitness in males but decreases fitness in females, and a second allele with opposite effects, is believed to influence the evolution of sexual dimorphism and sex chromosome evolution; both have evolved repeatedly among plant lineages, so understanding the potential for sexually-antagonistic variation informs the evolution of dioecy. Numerical analyses confirm the previous major conclusion that sexually-antagonistic polymorphisms are generally maintained in a larger region of parameter space if the locus is in the pseudo-autosomal region than if it is autosomal.Finally, I consider the effect of two stressors on time to flowering to address hypotheses regarding the evolution of flowering time in heterogeneous environments. A greenhouse experiment using Mimulus guttatus revealed that low water and herbivory had opposite effects on time to flowering, although these effects were weak. These stressors had stronger influences on plant height and the number of flowers produced. These data, combined with previously published results, suggest that a stressor's effect on non-phenological traits may influence the evolution of flowering time through mechanisms not considered by previously published theoretical studies.

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