Kimberly A. Hughes, PhD - US grants

Research Objective Number 21--Data collection in population aging (Biodemography) Understanding causes of these patterns is critical for demographers and public health specialists who interpret the patterns as they relate to, humans, and to biologists interested in the genetic and cellular processes causing aging. This project investigates potential biological causes of late-age mortality 'plateaus' that have been observed in cohort studies of both humans and fruit flies. The following potential causes will be studied using fully-factorial experimental design: a) genetic heterogeneity within populations ('demographic selection') b) changes in reproductive status and population sex ratio. c) changes in population density and environmental quality. d) changes in individual activity level and individual reproductive performance. Mortality patterns will be contrasted using a three-way factorial design involving the following treatment categories: genetically heterogeneous (outbred) populations vs. genetically homogenous populations (crosses between inbred lines); single sex (non- reproducing, constant sex ratio) populations vs. mixed sex (reproducing and variable sex ratio) populations; constant density populations vs. populations where density decreases with age. In concert with these treatments, we will assay activity level and reproductive success in aging flies from the different treatment categories. Associations between these individual- level traits and population-level mortality patterns will begin to address the question of whether mortality plateaus are caused by changes in individual mortality risk, rather than by demographic phenomena.

Behavioral and Genetic Mechanisms for Frequency-Dependent Survival and Mating Advantage in Guppies

IOB-0743990

Anne Houde

In the genomic era, it has become increasingly obvious that most traits that are relevant to the health, longevity, and fertility of organisms (including humans) are influenced by genetic variation (polymorphism). Despite intense interest in mapping and characterizing the responsible genes, the processes responsible for maintaining genetic variation are generally unknown. One reason is that direct experimental investigations are impossible in humans and difficult and expensive in most model organisms. More tractable species that can be studied in both natural and laboratory settings are needed to address this question. Wild guppies exhibit one of the most striking examples of polymorphism among animals (male color pattern variation), thought to be maintained by mating and survival advantages to rare or uncommon color types. Mating advantage appears result from female sexual responses to unusual males, and survival advantage appears to result from selective predation on common color types. This project will elucidate behavioral and genetic mechanisms underlying these patterns. Studies will examine (1) behavioral mechanisms leading to mating advantage for rare types, (2) behavioral responses of a predatory killifish to rare vs. common types and (3) brain gene expression changes that occur when guppies respond to novel sexual and environmental stimuli. Specific outcomes include determining (1) if female guppies have a specific preference for rare male types, (2) if prior experience with color types affects the predator's behavior and (3) which genes change their levels of expression in response to novel stimuli. This work will provide a clear picture of how behavioral and genetic processes contribute to genetic variation, and will also provide a model system for understanding response to novelty as a general phenomenon. Broader impacts of the project will include training of undergraduate and graduate students and further development of the guppy model system as a well-known exemplar for broad understanding of evolution.

Humans and other organisms are enormously genetically variable, even for traits like lifespan and fertility. During the past decade, genes affecting longevity and fertility have been discovered by mutating those genes in laboratory animals and observing the resulting effects. For example, mutations in genes controlling insulin signaling can increase the longevity of worms, flies, and mice by 100% or more. These results beg the question of whether the same genes are responsible for natural variation among individuals, populations, and species in longevity and fertility. This project addresses this question by discovering the genetic basis of life history differences in artificially-selected and in natural populations of an insect, Drosophila melanogaster, for which powerful genetic techniques are available. Expression profiling, genetic mapping, and new statistical techniques will be deployed to identify the genes contributing to longevity and fertility differences between populations.

Genes causing variation in longevity and fertility have significant impact on human health and well being. Most of the proposed candidate genes are shared between insects and mammals (including humans), and knowing which genes cause variation in non-inbred animals has important implications for biomedicine. Other significant effects will include training of undergraduate and graduate researchers in the laboratories of all three investigators, and at two ?mini-symposia? that will include all participants, and development of new analytical tools.

For decades biologists have struggled to determine whether and when individual behavior is influenced more by "nature" (genes) or "nurture" (social environment). While both are known to matter, emerging research suggests that "nature" and "nurture" are actually complex phenomena that are frequently difficult to disentangle. This question becomes even more complex when individuals are part of a social group. Therefore the goal of this project is to understand how social groups behave toward individuals with different sets of genes and how individuals with different genes might respond differently to the same social cues. One way to make this problem more tractable is to use tightly controlled experiments with an animal species in which specific behavioral differences are regulated by a single gene. The proposed research will use two genetically determined color forms of male mosquitofish that differ in the amount of aggression they display toward other members of their group. The experiments will determine how group composition affects the behavior of juvenile and adult fish. The studies will answer critical questions of the interaction between individuals and groups, such as how does living in a "high aggression" group affect the health and behavior of a juvenile fish, and does any effect of "high" vs. "low" aggression depend on the juvenile's own genetic makeup or is it regulated primarily by the social environment?

Upon publication data will be stored and available on DRYAD (datadryad.org. Results of these experiments will be broadly useful in understanding the factors that influence aggression and other social behavior in animals, including humans. In addition, the project will stimulate teaching and learning, increase research opportunities for students from underrepresented groups, and contribute to public understanding of science. The project will support the training of one female Ph.D. student, and will involve undergraduates from under-represented groups. The investigators will also develop a workshop on animal social behavior and genetics for Florida secondary school teachers as part of a funded "BioScopes" project. The workshop will consist of lectures and "hands-on" activities that can be adapted to the teachers' classrooms.

Genes shape how sensitive individuals are to environmental conditions during development, and this environmental sensitivity influences the behaviors produced in adulthood. This project seeks to understand how genes and developmental conditions together influence the brain, and how that alters social behaviors. The planned research takes advantage of extensive information on genetic and environmental influences on behavior of guppies, small fish that have evolved numerous behavioral responses to predators. Guppies that experience high and low levels of predation in the wild will be raised in laboratory conditions with and without predator exposure during development. Genetic and molecular experiments will link the patterns of gene expression in different brain regions to neural activity patterns and the resulting social behaviors. Results will demonstrate the extent to which similar behavioral traits (increased sociality in fish from high-predation sites and in fish exposed to predators) rely on the same gene expression changes and brain activity patterns, or whether similar behaviors may emerge from a variety of neural mechanisms. These findings will also reveal how sensitivity to environmental conditions shapes evolution of behavior. Developing this novel experimental approach will provide a model for other researchers seeking to understand the impacts of gene expression differences on behavior. The PIs will incorporate this research into undergraduate courses and will train graduate students via annual workshops on analysis of gene expression data. The simplicity and availability of guppies also make them amenable to enriching K-12 curricula in evolution and behavior, through development of a guppy module for for the Understanding Evolution resources for teaching evolution (http://evolution.berkeley.edu/). This project will allow the Colorado State University researchers to extend an ongoing program in which lab personnel work with middle school classes to design and implement behavioral experiments using guppies to reach a larger group of students.

Individuals are enormously genetically diverse, even when those individuals live close together in the same environments. This high diversity has important implications for sustainable agriculture and for the conservation of biodiversity because genetic diversity allows crops and wild plants and animals to persist in the face of disease and other environmental challenges. Understanding genetic diversity is also important in medicine because individuals have different susceptibility to disease and they can respond differently to the same treatment; this is the foundation of the recent emphasis on "personalized medicine". However, high genetic diversity is surprising because we expect that local populations that share a common gene pool and experience similar environments should be relatively genetically homogenous. This project addresses the debate about why individuals within populations (including humans) are so genetically diverse. Specifically, the research team will test a prominent hypothesis: that high diversity is maintained because rare gene variants confer an advantage to individuals who bear them (i.e., they are favored by natural selection). The project will also identify the genes that are the direct targets of this kind of selection. Because experiments required to answer these questions would be impossible in humans or agricultural species, the project will use a vertebrate animal that has well-known natural history, ecology, and behavior, and for which the genome sequence has recently become available (the Trinidad guppy). These small fish have high genetic diversity for body color, and this research will examine competing ideas about why: (1) fish with rare patterns survive better, or (2) fish with rare patterns reproduce more successfully. This project will also produce educational material and activities for school children. This material will enhance students' understanding of genetics, ecology, and evolutionary biology by using an animal with which many students are already familiar since guppies are popular in home aquariums.

Accounting for the persistence of high genetic diversity in ecologically-important traits is a fundamental problem in population genetics, and one that has fundamental implications for agriculture, medicine, and conservation biology. Debate about what processes maintain variation has led to the development of important population-genetic principles and hypotheses, but the larger question remains unanswered. This project will test the hypothesis that selection that varies in space or time ("balancing selection") maintains genetic diversity in natural populations and will link these selective processes directly to the genetic variants they target. Researchers will combine genomic and ecological approaches in a species exhibiting one of the best-known cases of adaptive polymorphism, the colour patterns in the Trinidadian guppy (Poecilia reticulata). Field and laboratory studies of predator density, reproductive behavior, and color-pattern variation will determine which ecological processes promote genetic variation. Whole-genome sequencing of guppies from 13 natural populations will identify regions of the genome enriched for intermediate-frequency alleles; using data from many populations will allow us to differentiate between loci under balancing selection and those that are polymorphic because of non-selective processes such as random genetic drift and migration. This multipronged approach will enable linking evolutionary processes that maintain variation directly to the genetic variants (polymorphisms) they target.

How do populations evolve in complex and changing environments? Why do some populations have the necessary genetic variation to adapt to environmental change, while others do not? This research proposes to answer these questions by combining ideas from genetics and behavioral biology. Instead of starting at the population level and working towards mechanisms, the investigators will instead start with the developmental processes that differ across individuals to produce variation that fuels evolutionary change. The focus will be on the relationship(s) between an individual’s choice of environment (e.g., where to live) and the developmental processes that are shaped by that environment (e.g., their later behavior and survival). The research will integrate theory, and experiments with fruit flies, to study the links between environment choice and development, and how these links differ between individuals, at the population, individual, and genomic scales, and across generations. This approach will develop and test new mathematical tools that will allow future researchers to predict the evolutionary consequences of environmental variation for any population. As part of this research, the investigators will mentor and train undergraduate students, graduate students, and postdoctoral researchers at multiple institutions for four years; and, they will run a summer research program for high school teachers to provide experience with hands-on research and guide them to develop lesson plans in mathematical theory and genetics for their classrooms. Therefore, this research will uncover fundamental principles of evolution necessary to predict population vulnerabilities to environmental change while training the next generation of leaders in science.<br/><br/>The goal of this research is to develop a comprehensive framework that links functional genetic mechanisms of trait expression with organism-level environment preferences to predict GxE within and among generations. The research will combine experiments and theoretical models. At the organismal level, the Aims will interrogate links between preference for a particular environment, and experience in each environment—and how these processes result in expressed patterns of plasticity and fitness. This approach will provide understanding of which individuals will be plastic, and why. The next step is to identify underlying gene expression networks that produce variation in behavior and functional links between environment choice and plasticity. Simultaneously, the investigators will develop population level theoretical models that will examine how variation in environmental exposures influences genetic variation in responses to environments, and how these processes together control the expression of GxE and influence its evolution. By coordinating experimental work and population-genetic models of the evolutionary causes of GxE, this research will provide biologists with a rigorous conceptual toolkit from which to interpret or apply these ideas to any organism. Together, these efforts will “put the pieces together” to produce a priori, bottom-up predictions about GxE and its evolution, predictions which are currently lacking. At the same time, the investigators will run a Research Experience for Teachers (RET) program, using established best practices. The RET will impact hundreds of students from underrepresented groups by enhancing the expertise of their teachers with critical hands-on biology research experience.<br/><br/>This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.