Janis Antonovics, PhD - US grants

While disease has been shown to be of enormous importance in agriculture, we know very little about the importance of disease in regulating natural plant populations. Most agricultural studies have investigated short-term impacts on genetically uniform varieties; effects of disease on long-term population fluctuations in nature are not understood. The present study will use the anther-smut disease of white champion to investigate the effects of a particular class of diseases (those transmitted by pollinators) on population regulation. The research will combine computer simulation with the study of disease spread in experimental populations, so as to understand the potential impact of the disease on the plant populations.

Genetic interactions between plants and their fungal pathogens have been studied for many of the major disease problems in agriculture, but little is known about host resistance and pathogen virulence in natural systems. Since it is widely thought that natural systems have fewer disease epidemics than crop systems, information on the distribution of genetic variation and the genetic basis for traits that control disease reactions in nature may prove useful in crop disease control. Past work on the anther.smut fungal disease of the white campion revealed that the likelihood of infection for a plant depended on the genetic identity of both the plant and the fungus. In the current study, the mode of inheritance of plant resistance and fungal virulence will be examined; methods will include testing progeny of genetic crosses in both field studies that mimic natural disease spread and in controlled greenhouse experiments. This research will begin to determine if the relatively simple single gene control of disease expression found with several crop plants also is prevalent outside of agriculture.

The abundances of many plant species fluctuate widely in natural populations. Close examination of some of the most simple mathematical models of population growth has shown that in addition to the effects of random environmental noise, fluctuations in population size (from periodic oscillations to chaos) may be part of the natural dynamics of many systems. These theoretical results are seldom tested because multi- generation experiments in controlled environments are often difficult and expensive to conduct. The investigators will use experimental populations to examine 15 generations of the population dynamics of Cardamine pennsylvanica, a small, rapidly- growing greenhouse weed. Using a greenhouse weed allows them to do experiments in ecologically "natural" conditions with the precision and ease of a controlled environment. Population dynamics may be affected by different environments. Hence, some experimental populations will have variable environments and others will not. Population dynamics may be affected by the genetics of the population. Hence, some experimental populations will have little genetic variability and others will have substantial genetic variability. Genetically uniform populations may be expected to evolve little, and exhibit purely ecological responses. These experiments are essential steps toward understanding to what extent populations dynamics are driven by ecological versus genetic processes.

Generalized host/pathogen models have shown that pathogens can theoretically regulate host population dynamics, as well as have evolutionary impacts. At the same time, there has been little or no work done to measure ecological or evolutionary relationships between hosts and pathogens outside of human epidemiology or agricultural crop systems. The major goals of this proposal are 1) to develop population dynamic models relevant to plant host/pathogen systems, 2) to extend the theory to examine the effects of genetics on population dynamics, 3) to develop models that explore evolutionary impacts of pathogens on host life histories, 4) to experimentally determine the effects of density dependence in Silene populations, and 5) to establish long term experimental populations that allow model assumptions to be tested, thus acting as a guide to future theory development.

Population dynamics and pattern formation in plant populations: theoretical models and empirical tests using two weedy annual species. The spatial position of plants in a population can have important consequences for both the population dynamics and the types of patterns produced in plant populations. The development of a series of models that explicitly examine the spatial position effects in plant populations is proposed. The theoretical models will be calibrated using empirical data from individuals of two species of weedy annuals, Cardamine pennsylvanica and Oxalis corniculata, grown under controlled environmental conditions. Each species will be grown with different numbers of neighbors and with different spatial positions of neighbors to determine plants response to different local neighborhood conditions. This information will provide the parameters for the plant population models. In addition, long term population studies of each species will be established, using the above two species, under controlled environmental conditions to determine how well the theoretical models predict the behavior of populations growing under semi-natural conditions. This study will help link through modelling the short-term processes responsible for the behavior of individual plants and the long-term behavior of populations through time. In addition, this study should also provide a theoretical framework for determining what sorts of processes produce patterns within populations.

Systems of interconnected populations (metapopulations) are likely to be the rule rather than the exception in nature. Nevertheless, the study of natural systems of interconnected populations has lagged behind theoretical demonstrations of their potential importance. Coloniation, extinction, and population interconnectedness play an important role in the dynamics of the Silence alba/Ustilago violacea plant-fungal pathosystem. This system is experimentally tractable and shows host genetic variation in resistance and susceptibility,. The proposed research will continue the long-term monitoring of metapopulation processes in natural populations, assess the effect of population connectedness on local dynamics using experimental populations, and investigate empirically and theoretically the effects of genetic compostion on metapopulation dynamics of host-pathogen systems. The results will provide information on the degree to which metapopulation processes influence host-pathogen systems and how genetic variation in the component species affects these processes. This system is of general interest because the metapopulation concept provides a framework for understanding the consequences of habitat fragmentation.

While traditional sex ratio theory predicts organisms will produce roughly equal proportions of the sexes, many species exhibit persistent sex ratio biases. Consequently, there now exists a rich diversity of theory pertaining to biased sex ratios. Meiotic drive, cytoplasmic inheritance and other non-Mendelian mechanisms of sex ratio distortion may play a major role in the evolution of biased sex ratios. Meiotic drive systems, including sex ratio distorters, may be central to our understanding of evolutionary processes such as sex chromosome evolution, the evolution and diversity of sex determining mechanisms, and the origin of sterility barriers between species (including Haldane's Rule). Initial research has shown that certain families of Silene alva, a dioecious plant, exhibit severely female biased sex ratios. Studies involving molecular markers of the Y chromosome show that the vias is present in the seed and is therefore, not due to a higher mortality of male progeny. Sex ratio bias is inherited through or expressed in the male parent. This pattern of inheritance and other circumstantial evidence lead one suspect and X-linked meiotic drive system may be responsible for the evolution of the female bias. The proposed research will determine the genetic basis of sex ratio distortion in Silene alba by using reciprocal crosses and backcrosses. RAPD markers, will be used to investigate specifically how and when the female bias develops. Crosses among geographically separated populations and among closely related species will be used to detect sex ratio distortion which is normally suppressed by restorers. Finally, whether the structure of natural populations of Silene alba is consistent with other mechanisms of selection for biased sex ratios will be determined. These results will provide information the nature and diversity of genetic mechanisms influencing sex ratio in natural populations. Moreover, because sex chromosome markers and wide crosses represent unique approaches to studying sex ratio genetics,it is expected that methods will stimulate research into mechanisms of sex ratio bias in other species.

9311635 Antonovics This study will focus on the parameters that affects the colonization process in plants. Specifically, the investigators wish to examine the role of genetic connections between small newly established colonies and the correlated rate of population increase. By studying both the genetic and demographic factors that influence the process of colonization in a common species, they will gain information useful for understanding the population dynamics of species made rare by habitat fragmentation. %%% The process of colonization in Silene alba will be studied experimentally three ways. First the investigators will establish founder colonies planted in an array with graded spacing intervals between colonies. Measurements of gene exchange between colonies will then be correlated with demographic attributes such as rates of colony growth. Secondly, they will investigate the effects of the relatedness of the founders and the role of isolation on colonization establishment by comparing artificial colonies established with genetically variable outcrossed colonists to colonies established with genetically inbred (sib-mated) colonists. Thirdly, the investigators will investigate the demographic effects of varying the number of individuals that found a colony. Finally, they will conduct demographic genetic studies of natural colonization episodes as they occur in a previously censused metapopulation of Silene alba to provide a natural backdrop against which to interpret the experimental results. *** tonovics This study will focus on the parameters that affects the colonization process in plants . Specifically, t $ / ! !. !. !. F ( Times New Roman Symbol & Arial * " h 6 e: e V Antonovics/Richards abstract Elizabeth M. Behrens Elizabeth M. Behrens

Antonovics 9408207 The ecological and evolutionary impact of sexually transmitted diseases (STD's) has rarely been studied in a non-medical context; they have been considered a minor type of infectious disease in natural systems. The investigators' initial studies have shown that STD's are abundant within the animal kingdom and that they have many shared characteristics (low disease induced mortality, long span of infectious period, narrow host ranges, sterility, less population cycling). This study will use theoretical models to investigate (a) the factors that influence evolution towards sexual versus other modes of disease transmission, (b) the coevolution of pathogen characteristics and host mating systems, and (c) the effect of spatial structure on stability and evolution of STD's STD's can have important consequences for population regulation and for the evolution of mating systems. The study of their population biology is also relevant for interpreting and predicting the emergence of new diseases. The present study will bear directly on these issues.

9321790 Antonovics This project is an investigation of the mechanisms governing population dynamics in Cardamine pennsylvanica, a weedy plant. In an earlier study, experimental populations of these plants displayed complex numerical dynamics over fifteen generations, with populations cycling from low to high density in three to four generations. Although simple models of density-dependent population growth predict that the oscillatory dynamics are possible, these models predicted stable (non-cyclic) dynamics when applied to our experimental populations. This project will investigate what factors responsible for the discrepancy between the model predictions and the observed dynamics. From this, the investigators extrapolate to when similar mechanisms might drive complex dynamics in natural populations. The significance of complex dynamics in nature is twofold. First, if these dynamics are the product of deterministic population regulation (as opposed to stochastic fluctuations in resource availability), then attempts to interpret the complexity of nature should focus on understanding the feedback mechanisms that drive these processes. Second, populations that are highly variable in size are prone to extinction due to demographic stochasticity, and may be unable to adapt to a changing environment due to increased probability of random genetic change. Thus, an understanding of population dynamics is crucial to interpreting basic ecological studies, as well as to environmental management. t v v ! ! ! F v v ( Times New Roman Symbol & Arial l " h * eX* eX* e 9 7 Crystal Blackshear Crystal Blackshear

Antonovics 9520754 The majority of plant species have both male and female flowers. However, some species have male and female flowers on different plants. Plant ecologists and geneticists are keenly interested in the forces that determine the transitions between these two types of breeding systems. The proposed research will study how this transition is being manifested in an herbaceous plant, Astilbe biternata, which has an intermediate breeding system. Understanding this transition will increase knowledge of how genes can be transmitted in plants and will help to plan long-term conservation strategies for dioecious species.

Antonovics 9520793 To evaluate the appropriateness of using a kin selectionist framework to explain worker behavior, the origin(s) of sex ratio differences between colonies of the ant, Leptothorax curvispinosus, will be elucidated. Oviposition sex ratios will be determined by flow cytometry (a novel application of this technology) and compared with the following year's adult sex ratios. A marked disparity between oviposition and adult sex ratios would suggest that workers may indeed manipulate brood sex ratios to their inclusive fitness benefit; possible mechanisms will be investigated experimentally. The possible role of historical distorter invasion will be explored through computer simulation and genetic models. Initial simulations of this "distorter invasion hypothesis" suggest an interpretation of eusociality that differs significantly from the kin selectionist explanation, in essence arguing that invasion creates predictable, oscillating mate limitations, and that worker behavior is an adaptive response under such circumstances.

9615317 Antonovics Plants are assailed by a wide array of pathogens, and these are a serious problem in agriculture. However, the role of pathogens in determining the abundance of species in the wild is much less well understood; epidemics seem rarer, pathogens are less apparent, and effects on plant abundance are not always self- evident. Over the past ten years, Dr. Antonovics and his colleagues have used the anther-smut fungal disease of the plant white campion (Silene alba) as a model system to understand how pathogens impact natural populations. Individual plants differ in their susceptibility to the disease, but the genetic basis of this susceptibility is not understood. It is also not clear why populations do not become completely resistant; presumably the genes determining resistance have negative side-effects. This research will investigate whether one or several genes are involved in susceptibility, localize these genes using DNA markers, and investigate the causes of the resistance cost. Dr. Antonovics will also investigate whether the resistance is general to many pathogens or specific to just this one fungus. Identification of resistance genes will allow rigorous study of how these genes are distributed in nature, and of the role they play in rescuing plant populations from the disease. This research will improve understanding of how pathogens control plant populations, and will therefore be of direct relevance to biological weed control and conservation biology. It will also open the door for the possible use of these resistance genes in developing resistant transgenic crops.

Over the past twenty years, evolutionary biology has developed in to a vibrant, investigative science with a potent relevance to societal issues such as origins of infectious disease and biotechnology. The emerging role of evolutionary biology as a scientific discipline is in stark contrast to the continuing efforts to limit teaching evolution in high-schools, or to question evolutionary ideas as a valid province of science. While the teaching of evolutionary biology at both high school and college levels is now struggling to emerge from such censoring and neglect, evolution is still largely taught as a theoretical, dialectical discipline that often seems only to impact on theoretical ideas and broad conceptual landscapes. Rarely is it taught as an experimental, analytical science of applied relevance on a par with, say, physiology or molecular biology. We propose to rectify this situation in two ways. First, we will develop an experimental investigative laboratory in evolutionary biology that can serve as a "flagship" for illustrating how evolution can be taught at the college level as an experimental and investigative science that is societally relevant. We also illustrate how such an investigative course could be run with minimal resources and using a wide range of possible materials. Second, recognizing that curricula and colleges will vary in terms of their ability or desire to commit to such a focused laboratory course, we will also stimulate the teaching evolution as a hands-on science by additionally developing a web-site for distribution via the internet of laboratory exercises in evolutionary biology. Currently, such a resource is not available, and we only know of one manual on teaching evolution as a laboratory course. We will therefore gather, collate, and distribute materials that can be used to enrich discussion sections and laboratory classes.

9801551 Antonovics and Pringle Models on reproductive ecology of mutualisms have not been well developed or tested. Considering sexual vs. asexual reproduction, it has been hypothesized that mutualistic species that live inside other species, for example arbuscular mycorrhizal fungi that inhabit plant roots, should be asexual which would allow the perpetuation of well adapted genotypes. Sexual reproduction, in contrast, would create novel genotypes that might be less adapted to a host. Information on the reproductive biology of mutualists is necessary to test this notion. I plan to describe the genetic system of arbuscular mycorrhizal fungi as a first step in evaluating the asexual-predominance hypothesis for mutualisms. I also plan to test the benefits to plants of associations with arbuscular mycorrhizal fungi. This is necessary since a non-mutual relationship between fungi and plants due to environmental conditions or differing interactions with specific plants would provide situations that are inappropriate for testing the hypothesis.

Host shifts of pathogens from animal species have lead to an increasing number of infectious diseases in humans. Studies of host shifts have been conducted primarily through the historical approach of tracing the epidemic's origin and identifying the reservoir host. While this is an important component of preventing disease transmission, the goals of the proposed research are to develop a more predictive approach to the study of host shifts and to attain a basic understanding of the ecological and genetic processes involved. The proposed research will combine phylogenetic data analysis with experimental microevolutionary studies to achieve these goals. The phylogenetic analyses will be used to determine the characteristics of hosts and pathogens that have favored host shifts in the past, and to use these characteristics to make predictions about the likelihood of future host shifts. Inoculation experiments will then be used to test these predictions. Studies will be carried out on the genetic and ecological basis of host shifts occurring in present day populations, and on the evolutionary and population dynamics of newly emerged pathogens. The fungal pathogen Microbotryum will be used as a model system. This pathogen is characterized by a large number of naturally occurring host-races, it is easily manipulated, and large experimental studies are feasible. This extensively studied natural plant pathogen system has already provided valuable insights into the biology of sexually transmitted diseases. This proposal will address these specific aims: 1. To use phylogenetic information to predict host shifts; and 2. To study host shifts in a population dynamic context, and thereby, a. Determine the population dynamics of pathogens on new hosts, b. Determine the role of genetic factors in the transmission of a pathogen to a new host, c. Determine the role of pathogen specialization in persistence on new hosts.

Antonovics
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It is commonly suggested that pathogens will evolve toward being harmless so as not to cause the extinction of the host population and hence of themselves. This idea has been disputed on the grounds that selection for reduced virulence would require differential extinction of whole populations, a process that has been considered to be slow and ineffective. This study will use theoretical models to investigate whether the evolution of reduced virulence can occur in situations where the host and pathogen are distributed over a large spatial area, but where their dispersal is much more local. Model assumptions will be tested using the anther-smut disease of white campion. This is as a well-studied disease that partly sterilizes its host.

Given present day concerns about emerging infectious diseases, it is important to understand why some pathogens cause very severe disease symptoms, yet others have only a small effect on their hosts. Disease symptoms can change over time as a result of pathogen evolution, but the predicted direction and mechanism of such change has been very controversial. This study will model the processes involved, and therefore help predict possible future directions of change in the severity of infectious diseases.

Most pathogenic fungi have two stages in their lifecycle. One stage is produced by fertilization and has chromosomes from both parents, whereas the other stage is produced by mechanisms similar to gamete formation, and therefore has only half the number of chromosomes (the haploid stage). Often, the two stages differ in the degree to which they cause disease. This study uses molecular biology and other experimental studies to explore the link between disease ecology and genetic structure of a plant pathogenic fungus where the haploid stage is avoided by a special kind of mating (intra-tetrad selfing). This study will use the anther-smut fungus, Microbotryum violaceum, as a well-studied model system.

Intra-tetrad selfing also occurs in a wide range of organism, including commercially and scientifically valuable fungi, plants, and insects (e.g. yeasts and fruit flies), but its consequences have never been explored empirically. The proposed research will therefore have relevance for understanding genetic variation in species with this breeding system and possible novel mechanisms for changes in pathogenic virulence.

Host shifts of pathogens from animal species have lead to an increasing number of infectious diseases in humans. Studies of host shifts have been conducted primarily through the historical approach of tracing the epidemic's origin and identifying the reservoir host. While this is an important component of preventing disease transmission, the goals of the proposed research are to develop a more predictive approach to the study of host shifts and to attain a basic understanding of the ecological and genetic processes involved. The proposed research will combine phylogenetic data analysis with experimental microevolutionary studies to achieve these goals. The phylogenetic analyses will be used to determine the characteristics of hosts and pathogens that have favored host shifts in the past, and to use these characteristics to make predictions about the likelihood of future host shifts. Inoculation experiments will then be used to test these predictions. Studies will be carried out on the genetic and ecological basis of host shifts occurring in present day populations, and on the evolutionary and population dynamics of newly emerged pathogens. The fungal pathogen Microbotryum will be used as a model system. This pathogen is characterized by a large number of naturally occurring host-races, it is easily manipulated, and large experimental studies are feasible. This extensively studied natural plant pathogen system has already provided valuable insights into the biology of sexually transmitted diseases. This proposal will address these specific aims: 1. To use phylogenetic information to predict host shifts; and 2. To study host shifts in a population dynamic context, and thereby, a. Determine the population dynamics of pathogens on new hosts, b. Determine the role of genetic factors in the transmission of a pathogen to a new host, c. Determine the role of pathogen specialization in persistence on new hosts.

There has been an increasing interest in incorporating explicit spatial structure into ecological models. This research will investigate the effect of spatial structure on the dynamics of populations at the edges and borders of their ranges. The investigators will develop analytic and numerical approaches using methods from theoretical physics. They will study the spatial patterns that develop at different types of population margins, and how these patterns change when margins are either expanding or retreating. They will investigate how the range of a population in one dimension (as along a stream or a coastline) might differ from that of a two-dimensional population in an identical environmental gradient. The investigators will also study the effect of biotic factors, e.g. pathogens, on marginal populations, and whether margins can act as host refugia.

The goal of this project is to increase general understanding of the dynamics of population margins, as well as to stimulate and direct the detailed study of such margins. In the past decade, the spatial analysis of populations has been greatly facilitated by rapid technical advances in mapping, remote sensing, and computation. A strong theoretical basis for the spatial structure of population margins is an essential guide for the interpretation of such data.

Infectious disease may substantially impact the health and stability of natural animal populations. White-footed mouse (Peromyscus leucopus) and deer mouse (P. maniculatus) populations have been found to fluctuate due to peaks in food availability from oak acorn masts. It is likely that intestinal pathogens identified in Peromyscus contribute substantially to population crashes. The goal of this project is to understand how infectious disease can cause animal populations to crash or cycle throughout time. Long-term data on demography and infection will be used to quantify the effect of disease on individual survival and fecundity. In addition, experimental field manipulations will demonstrate the causative effects and interactions of disease and food on population dynamics of Peromyscus.

The proposed experiments will help determine how infectious disease impacts natural animal populations. This work is important because for most animal-born disease outbreaks that infect humans we know little about what factors in the animal's ecology drive disease outbreaks. In addition, the general relationship between disease incidence and population abundance has important implications for the emergence of new pathogens in human and animal populations. Finally, this work will help resolve the critical ecological factors that drive disease in natural populations and threaten the survival of animal populations threatened by disease.

Unlike most organisms where the structure of the chromosomes (the karyotype) is relatively stable, in the fungus Microbotryum there is enormous variation in chromosome size and the DNA content from one generation to the next. Even within an individual, there can be large differences between its two chromosome sets. The reasons for this variation appear to be related to the reproductive system of the fungus where mating occurs among the gametes produced by one precursor cell (automixis). This mating system is very similar to that found in many other fungi, plants, and insects. This study will examine the consequences of changes in genomic structure for offspring viability, as well as the correlations between chromosome variation and the proportion of the genome consisting of highly repetitive sequences of DNA.

Understanding the dynamics of genetic variation is the basis not only for interpreting evolutionary processes, but also for rational approaches to plant and animal breeding and population management for conservation, disease prevention, and control of invasive species. Furthermore, even small changes in chromosome structure are frequently associated with severe abnormalities in humans and other systems. This study will help identify genetic processes that allow some organisms to cope and even adapt to genomic instability.

Intellectual Merit - Genes on autosomes, on sex-chromosomes, in mitochondria and chloroplasts, and those associated with transposable elements are inherited through different pathways and with different rules. Yet the occurrence of these elements within single individuals, whose phenotype they influence, creates complex evolutionary processes that influence phenomena such as chromosome evolution and genome restructuring. This planning grant has the goal of developing the angiosperm genus Silene and its associated pathogen Microbotryum as model systems for understanding the evolution and genetics of sexual reproductive systems. The Silene - Microbotryum community has successfully developed these species into model systems for the study of sex-determination and host-pathogen systems. The objective of this FIBR planning project is to organize this community around the development of a common set of genomic resources, to integrate the current workers in the field, and to reduce the duplication of effort in developing common resources. A research symposium will be held to achieve this goal and will include not only the scientists working on this system, but also a set of experts in genomics, molecular biology, and theoretical biology who share conceptual interests but work with other organisms. Subsequently, a workshop of the FIBR PIs will be held to develop the proposal itself. This project is centered on the strengths of this system with regard to answering questions that are not readily approachable in other model systems. These strengths include a broad range of systems within closely related taxa, intense knowledge of pathogen dynamics and its interaction with the reproductive system, and a profound understanding of the ecological and phylogeographic context of the evolutionary processes under consideration.

Broader Impact - This planning activity will draw together a diverse range of researchers representing a breadth of institutional types and a geographically disperse set. The research symposium emphasizes direct student and post-doctoral participation and builds on the ongoing outreach efforts of the principal investigators. The symposium and planning meetings will provide opportunities to develop further plans for enhancing educational and outreach opportunities as part of the anticipated pre-proposal. More generally, planning for the FIBR pre-proposal will include mechanisms to promote the integration of population dynamic and molecular approaches and help the career development of young scientists by crossing disciplines and emphasizing a broad and comparative approach.

Sex differences in infection rates are widespread in natural populations of organisms ranging from plants and invertebrates to amphibians, birds, and mammals. Sex differences are also characteristic of many human diseases, such as HIV. This study will develop a mathematical model to investigate the effects of sex-specific differences in transmission on disease dynamics. Experimental populations of Silene latifolia infected with the pollinator-transmitted fungal pathogen Microbotryum violaceum will be established to estimate the within- and between-sex disease transmission, as well as sex-specific differences in recovery, disease-induced sterility, and mortality. To complement the experimental work, natural populations will be marked to estimate transmission, recovery, and survival rates.

Studying disease dynamics in two-sex systems is fundamental for guiding disease control strategies in species of agricultural, medical, and conservation concern. This work will contribute to understanding the spread and maintenance of disease in natural populations. This issue is important because disease drives ecological abundance, and natural populations may act as reservoirs for diseases that are important in agriculture and for human health. These serious concerns make understanding disease dynamics in natural systems imperative.

This OPUS project will produce a book synthesizing 20 years of NSF funded research on a model host-pathogen system: anther-smut disease caused by the fungal pathogen Microbotryum. This research has led to discoveries that have informed numerous areas of biology, including important aspects of human disease such as the impact of sexually transmitted diseases, the forces determining emergence of new diseases, and how these forces interact with changes at the genomic level. This project will provide college and high-school teachers online lab exercises and related background materials for using this system in teaching the principles of disease biology.

Pathogens cause huge amounts of human misery, either directly or through the destruction of crops, domestic animals, and natural ecosystems. By producing a highly readable, entertaining, and informative book the investigators will show how the anther smut system has led to innovative discoveries that have traversed a wide range of disciplines. Numerous undergraduates and many graduate students have entered disease biology through hands-on research with this system, and this book will stimulate further research on principles central to some of the most severe threats to human health and welfare.

Two keys to developing control and prevention strategies for many of the most damaging infectious diseases threatening human health, agriculture, and wildlife conservation are determining and predicting the distribution of pathogens. Predicting the way infectious diseases will affect populations is greatly helped by understanding the contributions of both genetic and environmental factors to disease distribution. The investigators will test the relative importance of these factors in nature by using the anther-smut disease of alpine plants as a natural model system. This pathogen is found only at high altitudes across Europe, despite the abundance of hosts at lower elevations. Field transplants combined with experimental introduction of the disease will be used to test differences in its spread at low and high elevations, and to understand the factors responsible for its restriction to high elevations. The researchers will be able to test theories of disease spread and distribution with virtually no risk to commerce, agriculture, or human health. The results will yield key insights into how host-pathogen interactions affect natural populations, and will help to inform predictions concerning the spread of existing and emerging infectious diseases. Furthermore, the study will influence interpretations of changes in elevational distribution of alpine species, which are very sensitive indicators of global climate change.

This project provides opportunities for undergraduate students to gain research experience and academic training. The research will allow expansion of several ongoing collaborations, particularly with scientists abroad. In addition, because these experiments are located within a highly-visited public botanic garden they will continue to contribute to raising public awareness about disease biology.

This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).

Most organisms exist in populations that are distributed in irregular and often ephemeral patches. This research explores two fundamental consequences of this fact: the forces that create and destroy patterns of genetic variation across a landscape and how these spatial genetic patterns affect responses to disease epidemics and climate change. The research applies high throughput genomic tools to understanding the demographics and genetic dynamics in more than 800 spatially distributed populations. Objectives are to understand how the distribution of organisms in nature affects the establishment, persistence and proliferation of isolated populations, with a particular focus on disease epidemics and host resistance.

Understanding the genetics and ecology of interconnected networks of populations is of applied importance for conservation biology, management of genetically modified crops, invasion biology, and understanding the potential of species to respond to global change. The emphasis on disease dynamics and resistance also contributes to understanding the dynamics of human pathogens. The research involves training 10-15 undergraduate and graduate students in the interdisciplinary fields of ecology, genomics, and informatics, with training opportunities designed to enhance participation from members of under-represented groups.

Infectious diseases can be devastating to humans and agriculture, but much less is known about how disease affects natural populations. This study will investigate the impact of a fungal disease, anther-smut, on the distribution of alpine plants, and will serve as a model for assessing how sterilizing diseases affect natural populations. The study will be carried out in an area where there is heavy disease infestation on many species, and steep environmental gradients in multiple valleys, enabling systematic studies of the factors that influence disease processes at the margins of species distributions. Genetic and ecological experiments, theoretical models, and long-term monitoring will investigate how disease affects the limits of species' ranges and how marginal populations may be foci for disease emergence through transmission of infections between host species.

This research will enhance international collaborations, support local conservation efforts, and provide a field course, training and hands-on research experience in infectious disease biology for researchers and undergraduate students. Alpine regions are themselves fragile environments severely threatened by climate change and this study will establish baseline information essential for managing these plant communities in relation to disease and the rapid environmental changes that are occurring in this area.

In nature, populations of organisms are generally clustered into distinct patches that, over time, exchange migrants and perhaps suffer extinction and later recolonization. The genetic consequences of this dynamic population fragmentation has been studied in theory, but experimental studies have lagged behind because of the large quantity of long-term data that are required. The proposed research will close this gap using nearly three decades of data collected from hundreds of populations of a plant (white campion) and an associated disease (anther smut). With these data, we will be able to follow the genetics of local populations as they are born, exchange migrants, and possibly go extinct. These observations are important for understanding how genetics affects extinction and colonization success. More broadly, understanding the dynamics of interconnected populations is fundamental to predicting how disease outbreaks can occur from local patches, how invasive species spread, or how the genetics of species can be altered when they are rare or occur in fragmented habitats.

The major objective of the proposed research is to follow the process of extinction and colonization in interconnected populations and study how these processes create and destroy genetic diversity. This proposal builds on a now 28-year study of the numerical dynamics of Silene latifolia (white campion) and its pathogen Microbotryum violaceum (anther smut). This project uses a long-term population genetic approach to characterize numerous colonization and extinction events and to follow populations through time. Methods used will include long-term monitoring (eventually more than over 800 populations for >30 yrs) and continued genetic sampling (eventually >15yrs). High throughput genomic studies of Silene populations will provide unprecedented resolution of changes in genetic divergence, the parentage of newly established populations, gene flow during population expansion or contraction, the genetic consequences of seed banks and the importance of inbreeding and genetic rescue for population persistence. Also, broad demographic shifts have occurred during the course of this study, opening up the potential to explore the population genetics of non-equilibrium systems of both the host plant and the disease. The Silene/Microbotryum system has become a model for numerous labs, and this research will provide a publicly available long-term data set of demographic and genomic data, living collections, and DNA samples. This study will provide scientific training in timely important fields of ecology, genomics, bioinformatics, and computational biology.

This research will examine the epidemiological implications and evolution of multiple modes of disease transmission. Using simulation and theoretical analysis, general strategic models describing vector and aerial transmission in spatially extended populations will be developed concurrently with models applicable to anther-smut disease, a model system for studies of disease ecology in natural populations. Adaptive dynamics theory will be used to investigate how transmission mode evolves in response to different life history and epidemiological features. To apply that theory to a real-world system, this research will measure contributions of aerial and vector transmission in nature, study genetic variation and covariation in transmission mode in host populations, and look for the signals of transmission mode in natural populations where there is long-standing data on density and disease prevalence. This disease system is well characterized ecologically and genetically, and is a highly tractable model system allowing large and directed experimental studies of transmission modes in natural populations. A key advance is the formulation of transmission functions to take into account host spatial distributions, including the concept of a perception kernel to study vector transmission. Furthermore, the work breaks new ground by investigating the evolution of transmission mode itself, rather than the evolutionary consequences of transmission mode for other host and pathogen traits such as virulence. This study emphasizes that the evolution of transmission mode is a co-evolutionary process involving the interplay of both host and pathogen traits, as well as the biotic and abiotic environmental context.