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Genetic Variation and Evolution

Ecological Genomics

Amphibians around the world have been experiencing massive population losses and extinctions. Although these declines have been precipitated by a number of factors, the fungal pathogen Batrachochytrium dendrobatidis (Bd) is a devastating threat, infecting hundreds of amphibian species worldwide. Our work on disease-related declines in amphibians leverages whole genome sequences to understand: 1) The genetics of host/pathogen interactions: The primary thrust of our frog/chytrid work focuses on understanding the genetic changes associated with fungal infection of frog hosts from a whole-genome perspective. From the host perspective, we use whole genome expression assays to identify genes that are involved in frog response to Bd under different conditions. We leverage whole-genome data for the model frog species Xenopus tropicalis to make much of our lab-based immunogenetics work possible. From the pathogen perspective, we use both comparative and functional genomics to study genes that may be involved in Bd pathogenicity under different conditions. 2) The evolution of pathogenicity: We were involved in the initial whole-genome sequencing project for B. dendrobatidis and are now sequencing whole-genomes of a number of additional Bd strains. The resulting sequence data will provide a wealth of information about the biology of this basal group of fungi and provide insight into the evolutionary origin and spread of this emerging pathogen. 3) Applying genomics to ecologically important questions: One of our major research aims is to integrate functional genomics and organismal biology by applying genomic data to questions in nature. We have an ongoing interest in developing large-scale genetic resources for non-model species and diverse collaborations to better tackle evolutionary questions in complex natural systems.

Genetics of Adaptation

Understanding the processes that contribute to diversification and speciation is a central goal of evolutionary biology. Recently renewed attention has been given to ecological modes of speciation, whereby natural selection leads to rapid divergence. We have been working on a system involving color variation that lends itself to testing predictions from ecological speciation models. Three lizard species exhibit striking variation in coloration associated with geologically recent formations in the Chihuahuan Desert. Blanched color morphs inhabit the white gypsum dunes of White Sands, melanic color morphs are found on the black basalt rocks of the Carrizozo Lava Flow, and brown color morphs are associated with the surrounding desert soils. Our work on ecological divergence in reptiles focuses on understanding: 1) The genetic basis of adaptive traits: To develop a more mechanistic understanding of how organisms adapt to changing environments, we study the genetic basis of reptile color variation. Much of this work has focused to date on the melanocortin-1 receptor gene (Mc1r) because of its key role in the pathway that produces melanin in vertebrates. 2) The interaction between natural and sexual selection: The potential for natural selection across environmental gradients to lead to reproductive isolation is often mediated by coincident evolution of ecological divergence and mating preference. We evaluate the potential for interaction of natural and sexual selection in this system by conducting field based mate-choice experiments. 3) The demography of local adaptation: Using multi-species and multi-habitat comparisons, we endeavor to understand how population demography can influence organismal response to natural selection and how, in turn, demographic histories can be shaped by natural selection.

Comparative Phylogeography/Ecosystem Evolution

This project surveys genetic diversity in multiple elements of mesic forests of the Pacific Northwest in the context of explicit biogeographic and landscape hypotheses that make testable genetic predictions. The general objectives of this research are to differentiate the influence of past geological and climatic events from current landscape level processes on the geographic structure of genetic variation in several codistributed highland forest species. You can read more details on comparative pylogeography by following this link.

Divergence With Geneflow In Chipmunks

Determining the frequency and genetic impact of hybridization during animal speciation remains a central and unresolved issue in evolutionary biology. If reproductive isolation is incomplete when nascent species come into contact, even moderate gene flow may result in population fusion. Thus, recurrent hybridization among animal species has traditionally been viewed as rare. Alternatively, genetic factors underlying speciation may continue to accumulate between divergent populations despite on-going gene flow, eventually leading to the evolution of complete reproductive isolation. Consistent with this second model (divergence with gene flow), several recent studies have shown that closely related taxa may retain differentiation despite high levels of cryptic hybridization and introgression. The radiation of western American chipmunks (Tamias, subgenus Neotamias) represents an excellent study system for diversification with gene flow. Thus, we are estimating the phylogeny of the genus using a diverse array of data sets, including mtDNA, ncDNA. You can read more here.

Microbial Diversity

We are developing techniques and tools with which to infer the makeup of a microbial community from the DNA present in a sample without having to sequence the DNA or culture the microbes. We are particularly interested in microbial communities in the human microbiome. We are beginning to perform wetbench experiments in addition to our in silico and mathematical projects. Our goal is to understand why different ecosystems host the communities they do, and how those communities change in response to evolutionary dynamics. See our Microbial Community Analysis (MiCA) website.

Investigating the Evolution of Antibiotic Resistance in Bacterial Biofilms

Persistent bacterial infections, like the kind associated with cystic fibrosis or tooth decay, are known as biofilms: communities of bacteria embedded in an extracellular matrix that are notoriously resistant to antibiotic treatment. At present, doctors must remove the entire biofilm and associated organ system to treat a biofilm infection. Traditionally, it was thought that a hardy physical structure gave biofilms their resistance, but recent research has shown that biofilms harbor a great diversity of bacterial strains. This project will study the evolution of antibiotic resistance in biofilms, with two specific aims. The aims are to 1) evaluate the role of physical structure in biofilm antibiotic resistance and 2) test whether it is relaxed selection or direct selection that drives the evolution of more resistant strains. If the persistence of biofilms is related to evolutionary diversification, then disrupting this evolution could be the key to effective treatments.

Toward understanding molecular mechanisms for protein evolution in bacteriophage

Persistent bacterial infections, like the kind associated with cystic fibrosis or tooth decay, are known as biofilms: communities of bacteria embedded in an extracellular matrix that are notoriously resistant to antibiotic treatment. At present, doctors must remove the entire biofilm and associated organ system to treat a biofilm infection. Traditionally, it was thought that a hardy physical structure gave biofilms their resistance, but recent research has shown that biofilms harbor a great diversity of bacterial strains. This project will study the evolution of antibiotic resistance in biofilms, with two specific aims. The aims are to 1) evaluate the role of physical structure in biofilm antibiotic resistance and 2) test whether it is relaxed selection or direct selection that drives the evolution of more resistant strains. If the persistence of biofilms is related to evolutionary diversification, then disrupting this evolution could be the key to effective treatments.

Intercalator-modified Nucleic Acid Probes for Targeting of Double Stranded DNA

A method for efficiently targeting specific sequences of double stranded DNA (dsDNA) would be a great contribution to many aspects of genetic research. Recently, a dsDNA targeting method has been developed based on modified nucleic acids. These nucleic acids are modified with intercalators: molecules that bind to DNA and insert themselves into the DNA structure. However, this technique is still in its infancy. This project seeks to further refine and explore the scope of the technique by synthesizing and attaching more efficient intercalators. The modified probes would then be tested in an extensive series of biophysical characterization experiments, the results of which would be used to design novel, more efficient probes. This research will help in developing tools and methods for gene therapy.

Selenium homeostasis and anxiety: the role of the genotype

Selenium is a trace element that is critical for maintaining normal brain function in humans and other vertebrates. Selenium (Se) deficiency causes numerous neurological and psychological deficits. However, the practice of Se supplementation to treat human disorders of mood is controversial because it does not always work. This research group hypothesizes that variation in response to Se supplementation may have a genetic basis, and could be a key factor in creating effective medical treatment (i.e. "personalized medicine"). To test this hypothesis, this group seeks to improve their genotyping technology and to collect preliminary data characterizing variations in the zebrafish response to Se at the protein level. This data will be used for a larger study on the relevance of genetic variation in the response to Se supplementation.

Genetic factors underlying susceptibility to birth defects

In humans, genetic factors are known to contribute to the susceptibility of the fetus to various environmental agents. These agents can result in birth defects, and are known as teratogens. For instance, developing fetuses exposed to alcohol have a spectrum of predictable abnormalities, including reduced eye size (microphthalmia) in 90% of all cases. This study seeks to identify and characterize zebrafish strains that are susceptible or resistant to teratogen exposure. Through the knowledge gained in this study, the researchers hope to work towards their long-term goal of determining the mechanisms by which environmental teratogens cause developmental defects in the visual system.

Human Microbiome

The microbiota normally associated with the human body have an important influence on human development, physiology, immunity, and nutrition. The vast majority of these indigenous microbiota exists in a mutualistic relationship with their human host, while others are opportunistic pathogens that can cause both chronic infections and life-threatening diseases. Our studies on the human microbiome largely focus on the human vaginal ecosystem, which plays ion important role in protecting women against nonindigenous, invasive organisms (pathogens).

Microbial Succession

Glacial retreat and physical weathering of rocks and minerals expose new habitats inducing primary succession. While primary succession has been extensively studied in plant communities, little is known about succession in the bacterial communities of glacial forelands in the Arctic even though microorganisms have key roles in soil development, biogeochemical cycling, and plant succession.

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