1989 — 1993 |
Schaeffer, Stephen W |
R29Activity Code Description: Undocumented code - click on the grant title for more information. |
Molecular Population Genetics of Adh in Drosphila @ Pennsylvania State University-Univ Park
The objective of the proposed study is to analyze the intraspecific and interspecific variation of nucleotide sequences of a phenotypically monomorphic locus to determine the important evolutionary forces that generate and maintain nucleotide diversity in natural populations. Nucleotide diversity is the ultimate source of phenotypic variation which allows organisms to adapt to new environmental challenges in natural populations such as acquiring disease resistance. Thus, it is important to understand the evolutionary forces that modulate the levels of genetic variation in natural populations. In addition, the evolutionary dynamics of a genetic locus that is phenotypically simple must be understood before the evolutionary forces that shape the pattern and organization of nucleotide diversity of phenotypically complex loci can be ascertained. The proposed study will sample the nucleotide diversity of 100 nucleotide sequences of the alcohol dehydrogenase (Adh) region, a phenotypically monomorphic locus, from five natural populations of Drosophila pseudoobscura and one population of D. persimilis to test whether this locus fits the predictions of the neutral theory of molecular evolution. A phenotypically monomorphic locus should behave according to the predictions of the neutral theory in the absence of other evolutionary forces such as natural selection. Any departures from the predictions of the neutral model seen in the Adh region of D. pseudoobscura will suggest that the action of natural selection may shape the pattern and organization of nucleotide diversity at a phenotypically monomorphic locus.
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1991 — 1992 |
Kao, Teh-Hui (co-PI) [⬀] Schaeffer, Stephen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Molecular Evolution of Self Incompatibility in Plants @ Pennsylvania State Univ University Park
Organisms can become resistant to new diseases or utilize a new food source as a result of diversity in their genetic material which serves as raw material for the evolutionary process. Many mechanisms exist to increase or decrease the amounts of genetic diversity. Inbreeding, a mating system where closely related individuals mate to produce offspring, can reduce genetic variation in natural populations by increasing the probability that genes are identical by descent. In plants, inbreeding can lead to short-lived plants and reduced crop yields when the identical genes are lethal genes. As a result, some plants have evolved a self-incompatibility mechanism that prevents self-fertilization and the harmful effects of inbreeding. In many species of plants, the self-incompatibility function is encoded by a single gene. The self-incompatibility gene can not only increase genetic variation at the locus that encodes it but may also increase diversity of genes located nearby. The main objective of this research is to study variation of nucleotide sequences of the self-incompatibility locus of Solanum carolinense, the horse nettle, in order to determine the impact that the self-incompatibility mechanism has on this unique genetic locus and on nearby nucleotide sites.
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0.915 |
1998 — 2002 |
Schaeffer, Stephen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Organization of Nucleotide Diversity in the Inversions of Drosophila Pseudoobscura @ Pennsylvania State Univ University Park
Schaeffer 9726825 The research goals of this project are to test hypotheses about the genetic forces that modulate variation of chromosomal alterations that modify gene order known as inversions. The chromosomal inversions on the third chromosome of Drosophila pseudoobscura have figured prominently in the literature of evolutionary biology for more than fifty years. They have proven to be a very useful model system for studies of geographic variation, natural selection, gene flow, and genetic drift. The inversions seem to represent a clear case of adaptive selection because they vary in frequency with the environment, form classical clines, and in some populations there are seasonal cycles of inversion frequency. The objective of this proposal is to determine how selection acts on the genetic contents of inversions within and among D. pseudoobscura populations. This research will discriminate between various models of selection by analyzing nucleotide diversity of nine PCR amplified markers uniformly distributed on the third chromosome of D. pseudoobscura. The nine markers will be sequenced in D. pseudoobscura strains collected from four populations that span an inversion frequency cline. Studies of molecular evolution over the past two decades have focussed on the genetic forces that shape diversity of single genes and have not considered if selection maintains assemblages of linked genes on chromosomes. It is an open question whether the association of genes on particular chromosomes within the genome happened due to selection or accident. Inversions provide an important mechanism to maintain the association of genetic diversity distributed across long distances of chromosomes. This project will provide valuable data on the genetic forces that modulate the evolution of large segments of the genome in natural populations.
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0.915 |
1999 — 2000 |
Whittam, Thomas Clark, Andrew Schaeffer, Stephen Swalla, Billie |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Automated Dna Sequencer and Dhplc Heteroduplex Analysis For Molecular Evolution and Development @ Pennsylvania State Univ University Park
ABSTRACT 9970256 Funds will be used to purchase an Applied Biosystems Prism 377 automated DNA sequencer and a Transgenomics WAVE high performance liquid chromatograph (dHPLC) to be shared by developmental and molecular evolutionary geneticists in the Institute of Molecular Evolutionary Genetics (IMEG) at Penn State University. These instruments will be used to establish a flexible, efficient, and cost-effective sequencing and genotyping facility. The strategy will employ a stratified sequencing approach, using dHPLC to identify fragment differences and automated sequencing of distinct fragments. The stratified approach is a rapid and proficient method for assessing DNA polymorphism in population-sized samples.
The four principal investigators will use these instruments in a set of overlapping projects that integrate developmental and evolutionary genetics in a wide range of organisms. The projects include: Molecular variation in genes associated with adaptive evolution (Andrew Clark). Sequence analysis will be used to explore variation in the regulation of genes encoding metabolic enzymes in Drosophila. In addition, combined analysis of functional variation and DNA sequence polymorphism will be performed to characterize and quantify the molecular evolution of antibacterial defense in Drosophila and maternal-zygotic gene expression in early development; Organization of nucleotide diversity in the third chromosomal inversions (Stephen Schaeffer). Comparative DNA sequence analysis will be used to determine the interplay of selection, drift, and linkage in determining observed patterns of genetic variation in the classical third chromosome inversions of D. pseudoobscura; Genetic regulation of early development and associations with interspecific differences in body plans (Billie Swalla). This project is investigating the evolution of body plans by identifying the genes responsible for morphological differences between closely related species of ascidians in the genus Molgula. Molecular phylogenies will be determined and candidate developmental genes that may be responsible for morphological evolution will be examined in hemichordates and urochordates and; Genetic basis of experimental evolution of virulence (Thomas Whittam). Molecular methods render the evolution of virulence amenable to direct study in the laboratory. Following a regime of experimental evolution in a microbial host-parasite system, this project will compare ancestral and derived strains of Legionella and identify specific nucleotide substitutions at known virulence-associated loci used to exploit protozoan hosts. In addition to these major projects, creative use of dHPLC and DNA sequence and fragment analysis is outlined by an additional eight minor users who are active members of IMEG.
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0.915 |
2003 — 2005 |
Schaeffer, Stephen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: Molecular Evolution of Extracellular Hemoglobins in the Vestimentiferan Tubeworm Ridgeia Piscesae @ Pennsylvania State Univ University Park
The tubeworm Ridgeia piscesae of the hydrothermal vents in the northeast Pacific Ocean uses extracellular hemoglobins to deliver environmental sulfide to intracellular bacteria, which in turn uses sulfide to create sugars for the host. R. piscesae displays several different growth forms depending on the temperature and chemistry of vent fluids. The growth forms of R. piscesae are genetically identical, but why R. piscesae shows variation in body shape in different environments is a mystery. This research will characterize sequence diversity and gene expression differences of hemoglobin subunits in two R. piscesae growth forms to determine if this candidate molecule responds to environmental variation in sulfide levels. Mapping the location of globin genes within the tubeworm genome will provide a better understanding of how these genes are regulated.
Hydrothermal vents are unique environments on this planet because organisms use chemical energy rather than sunlight drives the ecosystem. Genetic studies of Ridgeia piscesae will provide more insight into how organisms adapt to extreme environments. This research will provide a unique opportunity to learn if gene expression is influenced by the environment. Elucidating patterns of DNA sequence variation in globin genes will also increase our understanding of how environments influence patterns of evolution.
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0.915 |
2003 — 2009 |
Schaeffer, Stephen Akashi, Hiroshi (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Translational Selection and Molecular Evolution in Drosophila @ Pennsylvania State Univ University Park
This project will combine experimental and computational approaches to demonstrate the role of weak selection in Drosophila genome evolution. Both amino acid-altering and "silent" mutations in protein coding genes may affect the rate and accuracy with which proteins are synthesized. Genome sequence and expression data will be employed to identify amino acids that allow efficient translation. DNA sequence comparisons among close relatives of Drosophila melanogaster will determine whether selection for efficient synthesis acts as a global force in protein evolution. Mutations with subtle effects on cell physiology may play a major role in biological adaptation. However, because the fitness effects of "nearly neutral" mutations lie well outside the range that can be measured directly, comparative DNA sequence analyses may provide the only means of identifying such forces in natural populations. Understanding the forces that constrain protein evolution will inform the design of genes for heterologous expression and DNA vaccination and will aid in identification of homologous proteins in humans and model genetic organisms. This research will also provide opportunities for educators and high school students to conduct summer research projects in genome evolution. In addition, a database of Drosophila DNA sequences will be made publically available.
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0.915 |
2006 — 2008 |
Schaeffer, Stephen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: Population Genetics of Drosophila Pseudoobscura Segmental Duplications @ Pennsylvania State Univ University Park
How natural selection, genetic recombination, and genome structure affect the evolution of recently duplicated genes in Drosophila pseudoobscura will be examined using DNA sequences from natural populations and other species. Rates of evolution between duplicates will be compared; unequal rates would suggest that gene duplicates are under different selective regimes. Multiple individuals will be assayed for the frequency of the duplications to test whether the recent duplications have rapidly increased in frequency due to selection. Statistical tests will be used to detect signatures of natural selection and genetic recombination in the sequences of the duplications. Duplications on different chromosomes (one inverted and one non-inverted) will be studied to determine what role genome rearrangements play in the early evolution of duplicated genes.
Gene duplication is an important evolutionary mechanism that can lead to the evolution of genes with new functions. The availability of genome data from closely related species has exposed numerous gene duplications at various stages in the evolutionary process. This study represents one of the first attempts to gain insights into the early stages of the evolution of duplicated genes. Undergraduate students will be given the opportunity to participate in data collection, and they will learn valuable molecular techniques such as PCR, gel electrophoresis, and DNA sequencing.
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0.915 |
2009 — 2013 |
Schaeffer, Stephen |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Collaborative Research: Understanding Whole-Genome Evolution Through Petascale Simulation @ Pennsylvania State Univ University Park
This award is funded under the American Recovery and Reinvestment Act of 2009 (Public Law 111-5).
This research will address critical issues through a collective research effort to develop new algorithms and high-performance software development for data analysis. With the deployment of petascale computing systems, these problems can for the first time be addressed at scale. Nuclear genomes such as Drosophila will serve as the primary source of data to assess models and methods developed and this research leverages past work on the Genome Rearrangement Analysis through Parsimony and other Phylogenetic Algorithms software suite.
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0.915 |
2011 — 2014 |
Schaeffer, Stephen W |
R01Activity Code Description: To support a discrete, specified, circumscribed project to be performed by the named investigator(s) in an area representing his or her specific interest and competencies. |
Genomic Mechanisms of Chromosomal Rearrangements in Drosophila Pseudoobscura @ Pennsylvania State University-Univ Park
DESCRIPTION (provided by applicant): Chromosomal inversions are often detected in humans when individuals present symptoms of genetic diseases. Individuals with two different inversions can have lower fertility because genetic exchange between inverted chromosomes can lead to the formation of sperm or eggs with less or more genetic information. Inversions, however, can also be present in populations at high frequencies with no apparent negative effects on viability or reproduction. This proposal will test hypotheses about how inversions arise, spread, and are maintained in populations. Drosophila pseudoobscura is a model system for the study of inversions because its third chromosome is polymorphic for over 30 different gene arrangements in populations. These arrangements were generated through a series of overlapping paracentric inversions. The inversion frequencies vary among populations forming clines or gradients whose major frequency shifts occur with major climatic zones in the southwestern United States. The gene arrangement frequencies cycle with the seasons and show altitudinal clines. Population cage experiments in the laboratory have shown that different gene arrangements are maintained at stable equilibrium frequencies. This study will use next generation technologies to re-sequence 50 strains of D. pseudoobscura that carry one of six major chromosomal arrangements. Next generation sequencing analysis of mRNA will be used to quantify expression differences among the six different inversion backgrounds for two different Drosophila life stages, larvae and adults. The re-sequencing data will identify inversion breakpoint sequences and improve the D. pseudoobscura genome assembly. The transcriptome data will be used to improve the annotation of gene models in D. pseudoobscura. Molecular population genetic analyses of nucleotide polymorphism and gene expression data will test four classes of hypotheses about how a new inversion spreads through a population: (1) indirect effects due to reduced recombination leading to chromosomes free of deleterious mutations or enhancing the linkage of adaptive genes; (2) genetic drift that fixes underdominant arrangements; (3) direct effects of the chromosomal lesion such as alteration of gene structure or expression; or (4) genetic hitchhiking with an adaptive allele. These analyses will test two hypotheses about how inversions are maintained in populations: (1) by overdominance; or (2) as a protected polymorphism. Genes that show differential expression or protein variation may be manipulated in future experiments designed to understand the molecular genetic basis that underpins inversion evolution.
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2012 — 2014 |
Schaeffer, Stephen Cowart, Dominique (co-PI) [⬀] Cowart, Dominique (co-PI) [⬀] |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: Species Distributions and Population Structure of Escarpia Cold Seep Vestimentiferans @ Pennsylvania State Univ University Park
Deep-sea hydrocarbon cold seeps are unlike most environments on Earth, as life there is not reliant on the sun for energy. Despite the lack of sunlight, cold seeps support a diverse collection of organisms that rely on the seepage of oil and gas from the sea floor. Tubeworms are a group of animals that are important for these habitats as they form bushes that provide food, living space and protection for a variety of other animals. Due to their dependence on irregularly occurring seepage, tubeworm communities can be separated by hundreds of kilometers. Currently, there is little information available about how tubeworms are transported to inhabit these patchy environments. The proposed research will identify different tubeworm species as well as determine how transport and colonization of tubeworms connects the various cold seep sites in the Gulf of Mexico, West Angolan Basin (West Africa) and the eastern Pacific off of California. This research uses genetic tools and environmental data to improve human understanding of how unique cold seep communities are established and maintained.
Cold seep organisms use oil and gas as energy sources, illustrating that life can thrive even under the most extreme conditions. This work will determine how natural and anthropogenic factors impact these specialized ecosystems. Given that the future of deep-sea habitats remains uncertain, it is critical to increase knowledge of these organisms, as they are vital to the foundation of these remarkable habitats.
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0.915 |
2020 — 2021 |
Chiaromonte, Francesca (co-PI) [⬀] Makova, Kateryna (co-PI) [⬀] Schaeffer, Stephen W |
T32Activity Code Description: To enable institutions to make National Research Service Awards to individuals selected by them for predoctoral and postdoctoral research training in specified shortage areas. |
Computation, Bioinformatics, and Statistics (Cbios) Training Program @ Pennsylvania State University-Univ Park
PROJECT SUMMARY The Penn State ?Computation, Bioinformatics, and Statistics (CBIOS) Predoctoral Training Program? will train a new generation of scientists with strong computational, statistical, biological, and science communication skills to enable them to develop and lead interdisciplinary collaborative research efforts that promote advances in the biomedical and life sciences. The goals of CBIOS are consistent with the ?Bioinformatics and Computational Biology? program at National Institute of General Medicine. The aim is to train a new class of scientists with a primary identity as computational biologists/bioinformaticians, and whose disciplinary core draws from an emerging set of principles on how to compute, analyze, and apply biological data. The goals of the first five years of the CBIOS program were to train students ?that can think statistically, use computational and statistical tools, and generate computational and statistical innovation to keep pace with the quickly evolving landscape of high-throughput genomics technologies.? The second cycle of CBIOS will continue to provide a strong foundation in quantitative and life sciences, and incorporate a new science communication curriculum aimed at developing fluency in communicating the purpose, significance, and outcomes of research to diverse stakeholders in the science, medicine, policy, and business arenas. CBIOS builds upon six established graduate programs including four departmental and two intercollegiate programs. Training faculty participating in the program belong to five different colleges and two campuses ? providing a broad and interdisciplinary research spectrum. Most of the training faculty are affiliated with the intercollegiate Bioinformatics and Genomics graduate program and belong to centers of excellence under the auspices of the Genome Sciences Institute, which provides a common platform for interactions. Our faculty interact closely ? as evidenced by joint authorship on research publications, co-funded grants, co-teaching, and co-advising of graduate students. They have a combined annual research funding base of $75,265,600 direct cost, offering a solid foundation for trainees? research experience and opportunities. Combining NIH and Penn State support, CBIOS plans to train a minimum of 18 predoctoral trainees over a period of five years. Each trainee will be supported for two years (year 2 and 3 of their graduate career) while receiving a foundational curriculum through the CBIOS program. Trainees will gain a thorough understanding of the scientific process, responsible conduct of research, fluency in research methodologies, ability to utilize computational, bioinformatics and statistical tools in large-scale genomic data analysis, excellence in communication to diverse audiences, leadership in cross-disciplinary research teams, and excellent professional developmental activities. After the two years of support, trainees will continue to participate in monthly trainee meetings and remain connected with program activities throughout their graduate career.
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