2005 — 2009 |
Kopp, Artyom |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Genetic Basis of Morphological Evolution in the Drosophila Bipectinata Species Complex @ University of California-Davis
Genetic basis of morphological evolution in the Drosophila bipectinata species complex.
A key challenge in biology is to understand the genetic and molecular mechanisms of phenotypic evolution and speciation. What changes in DNA sequences are responsible for morphological innovations? How do these changes affect development and translate into phenotypic diversity? And what evolutionary forces promote these changes? These questions can best be addressed by analyzing the developmental genetic basis of phenotypic differences among closely related species. To be useful for this type of research, model species must show considerable phenotypic divergence, yet at the same time be accessible to genetic analysis. These conditions are met superbly in the Drosophila bipectinata species complex - a group of four closely related species that belong to the same lineage as D. melanogaster. Species of the bipectinata complex display dramatic variation in sexually dimorphic morphological traits, including cuticular pigmentation and sex comb morphology. The bipectinata complex is a product of a very recent evolutionary radiation. Its member species are separated by low genetic distances and hybridize easily in captivity. Dr. Kopp will use these features of the bipectinata complex to map the genes responsible for inter- and intraspecific divergence in pigmentation and sex comb morphology; to identify some of these genes at the molecular level; to test whether the same genes are responsible for phenotypic differences within and between species; to characterize the expression of candidate genes, and investigate whether evolutionary changes in gene regulation are responsible for morphological divergence; and to analyze molecular variation at candidate loci, and identify DNA sequence changes that may be responsible for morphological differences. Another important outcome of this project will be the development of a new model system for the study of morphological evolution, reproductive isolation, sexual selection, and the genetics of subdivided populations. Towards this goal, Dr. Kopp will develop genetic and physical maps for two species of the bipectinata complex, and maintain a collection of isogenic, recombinant, and mutant genetic strains that will stimulate future research in this model.
This work will have a broad impact on science and society by promoting cross disciplinary training of graduate and undergraduate students.
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2006 — 2010 |
Kopp, Artyom Nuzhdin, Sergey |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Connecting Molecular and Phenotypic Variation in Drosophila @ University of California-Davis
Recent technological advances have enabled large-scale analyses of molecular variation in natural populations. Very little is known, however, about the phenotypic consequences of this variation. The goal of this project is to understand the mechanisms that translate DNA sequence variation into phenotypic differences among individuals, using the Drosophila bab gene as a model. bab is responsible for a large proportion of variation in sexually dimorphic traits in natural populations. In this project, the entire bab genomic region will be sequenced from 100 Drosophila lines that show different phenotypes in order to identify DNA sequence changes associated with phenotypic variation. The level of bab gene product will then be quantified in the lines that show the greatest phenotypic differences, and the effects of each molecular polymorphism on gene activity will be determined. These data will be used to develop a quantitative model that links variation in DNA sequences to differences in individual development and, ultimately, in adult traits.
This project will facilitate the development of individualized approaches to human health by facilitating and understanding of the mechanisms that connect genetic variation to health and environment - that is, not only which DNA sequence changes are responsible for trait variation, but also how these changes produce different phenotypes, and why do they vary in nature. This work will also provide opportunities for undergraduate students to acquire first-hand research experience in evolutionary biology.
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2008 — 2013 |
Kopp, Artyom |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Developmental Basis of Convergent Evolution of Drosophila Pigmentation Patterns @ University of California-Davis
It is common for similar anatomical structures and physiological processes to evolve independently in different species of animals and plants. This phenomenon (known as convergent evolution) reflects the fact that similar ecological pressures impose similar functional requirements; in other words, each task calls for a specific tool. What is not clear is whether convergently evolved traits share the same genetic and molecular basis. It is possible that different molecular pathways can be co-opted in different evolutionary lineages to produce superficially similar structures and adaptations. This hypothesis will be tested by identifying the genes responsible for evolutionary changes in color patterns in several species of fruit flies (Drosophila). Drosophila has been chosen as a model for this research due to the ease and low cost of genetic and molecular experimentation in this insect. If different genes are found to produce similar color patterns in different species, it will indicate that natural selection can utilize different sources of variation to achieve the same functional outcome. An opposite finding will suggest that the action of natural selection is constrained by the inherent structure of genetic pathways that control animal development. Given the increasing importance of understanding adaptive processes in human pathogens, agricultural pests, and other biological species that affect human society and economy, resolving this interplay between chance and necessity in evolution will help in the development of biological and chemical control strategies. An additional goal of this project is to train young scientists prepared to take the lead in analyzing molecular variation on genome-wide scales, and relating it to anatomical and physiological traits and environmental factors. Such training is essential for further advances in human medicine, agriculture, forestry, and biotechnology. This project will provide an opportunity for students to acquire first-hand research experience and expand their career options by complementing theoretical education with a practical application of the latest concepts and techniques.
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2009 — 2012 |
Kopp, Artyom |
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. |
Genetic and Developmental Mechanisms of Evolutionary Innovations @ University of California At Davis
DESCRIPTION (provided by applicant): Morphological, physiological, and behavioral differences between humans and other primates are partly due to evolutionary innovations that arose in the human lineage. Understanding how and why these innovations evolved is a central motivation for sequencing the chimpanzee and other primate genomes. Interpreting the rapidly growing amounts of comparative sequence and gene expression data will require an integrated conceptual framework that connects molecular and phenotypic evolution. In this project, such framework will be developed in a Drosophila model, which allows genomic and population-genetic data to be combined with genetic crosses and experimental analyses of gene regulation and function. A powerful experimental model will be provided by a sex-specific morphological structure that originated and diversified recently in Drosophila evolution. The first goal of this project is to identify DNA sequence changes and population-genetic forces responsible for the origin and loss of regulatory interactions between genes that control the development of this structure. To accomplish this, biochemical, genetic, and comparative approaches will be combined to reconstruct the evolution of transcription factor binding sites in the regulatory region of a key gene that controls sex-specific differentiation, and examine the effects of natural selection on the sequence and affinity of these sites. The second goal is to identify the genetic and molecular changes responsible for the remodeling of a sex-specific developmental pathway on microevolutionary timescales. Comparative analysis of gene expression will be combined with genetic crosses and transgenic assays to understand how evolutionary changes in gene regulation affect cell differentiation and generate new morphogenetic pathways that shape adult morphology. These approaches will then be extended to a wider range of models to elucidate the genetic and developmental changes responsible for the origin of a novel sex-specific organ, and to test whether convergent morphological changes in different evolutionary lineages were caused by similar changes in development. The final goal of this project is to identify the genes and DNA sequence changes responsible for the recent origin of a unique sex-specific sensory system. This will open the way for understanding the molecular-genetic and neurobiological mechanisms of evolutionary changes in behavior. PUBLIC HEALTH RELEVANCE: The fundamental principle of sexual development - that sex-specific regulators act by modulating the output of other developmental pathways - is shared by all animals, including humans. Model system research that elucidates the molecular mechanisms and evolution of sexual differentiation will lead to a better understanding of the origin and development of sex-specific traits in humans, opening the way for designing drugs and prophylactic treatments that target male- or female-specific developmental pathways.
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2011 — 2013 |
Signor, Sarah (co-PI) [⬀] Signor, Sarah (co-PI) [⬀] Kopp, Artyom |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: the Developmental Basis of Convergent Evolution @ University of California-Davis
This research investigates the genetic basis of pigmentation differences in fruit flies of the genus Drosophila. It is a part of an effort to develop Drosophila pigmentation as an evolutionary metamodel. Established metamodels are necessary for the elucidation of any general rules in evolution. They test whether certain traits and gene networks evolve in a reproducible fashion. Previously the regions involved in color pattern evolution in one species pair were identified, and the genes are in the process of being characterized. This grant will improve this dissertation through funding an analysis of the chromosomal regions involved in pigmentation differences in an additional species pair. This comparative component will be integral to the formation of an unbiased understanding of the dynamics of convergent evolution in this system.
Metamodels are being actively developed in several systems, such as sticklebacks and mice. None of these endeavors account for the effect of network structure in shaping the dynamics of parallel evolution. Within Drosophila this is possible as most, though not all, genes in the pathway have been characterized. Furthermore--in addition to its scientific merit--this research generates opportunities for training in research and includes individuals from underrepresented groups. Undergraduates from this lab have continued on to graduate school and participated in local and national research symposia. This research is also being used to develop to develop lesson plans that promote engaged learning and improve biology education.
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2013 — 2017 |
Kopp, Artyom |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Convergent Evolution of Color Patterns Through Changes in Different Genes @ University of California-Davis
Different animals often evolve similar adaptations, reflecting similar functional pressures acting on different species. This phenomenon is known as convergent evolution and, although it has been widely acknowledged by biologists for more than a century, its genetic and molecular basis remains poorly understood. Our previous work has shown that seemingly identical traits can evolve by changes in different genes in different species. In this project, a combination of genomic, molecular-genetic, embryological, and comparative approaches will be used to identify the responsible genes in each of several independent cases where similar traits have evolved. Two key questions will be addressed by this work. First, what features of animal development allow it to translate different genetic changes into outwardly identical morphological characters? Second, since evolution can clearly take different genetic paths to produce the same trait, is the course it actually takes determined primarily by the intrinsic features of the organism, by its population history, or by the vagaries of chance that are known to play a large role in the origin of genetic variation? As synthetic biology (the design or artificial biological organisms with desirable properties) begins to move from speculation to reality, understanding the flexible wiring of natural genetic pathways that permits multiple solutions to the same functional problem will inform the design of synthetic gene networks. The wide variety of techniques and integrative approaches used in this project will advance the training of young scientists who will be able to understand the inner workings of biological systems and to apply these lessons to practical problems.
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2014 — 2016 |
Kopp, Artyom |
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. |
Molecular Genetics of Sex-Specific Evolutionary Innovations @ University of California At Davis
DESCRIPTION (provided by applicant): Most animal species are sexually dimorphic, yet the features distinguishing males from females are different in every case. This simple observation implies that new sexual characters are gained, and old ones are lost, during the evolution of any animal lineage. The rapid turnover of sex-specific traits is as obvious in humans and their closest relatives as in other species, but the molecular mechanisms of this turnover are not well understood in any animal group. To address this critical gap in our knowledge, we will use the Drosophila model to identify the genetic changes responsible for the origin of new sexually dimorphic characters. Powerful transgenic technologies allow us to manipulate genome sequence and development in Drosophila in ways that are not possible in any other animal model. Recent work in our lab suggests that the origin of novel sex-specific traits is linked to evolutionary changes in the spatial regulation of doublesex (dsx), a transcription factor that controls sexual differentiation in most somatic tissues. This hypothesis represents a major departure from the previously accepted models, which ascribed the evolution of sexual dimorphism to changes in the target genes regulated by dsx. In this project, we will use a combination of several recently developed transgenic techniques to carry out a rigorous experimental test of the new model. We will focus on the sex comb - a strictly male-specific array of modified sensory organs that evolved recently within the genus Drosophila and shows dramatic diversity among closely related species. Our previous work has shown that sex comb development requires localized expression of dsx and sexually dimorphic expression of the homeotic gene Scr. In species that primitively lack sex combs, dsx expression is absent in the corresponding tissue while Scr expression is sexually monomorphic, suggesting that the origin of sex combs was caused by changes in dsx and Scr regulation. We have identified the DNA sequences (called CREs) that control dsx and Scr expression, and will now characterize the functional impact of the evolutionary changes in these sequences. First, we will compare the regulatory activities of CREs from species with different sex comb morphology and species that lack sex combs, and test whether the origin of the sex comb coincided with the origin of new CREs that drive gene expression in the cells that give rise to this structure. Second, we will replace the dsx and Scr CREs in D. melanogaster with homologous DNA sequences from species with different sex comb morphology and species that lack sex combs, and test whether these replacements are sufficient to eliminate the sex comb or change its appearance. Finally, we will extend this work to other sex-specific structures that evolved independently in distantly related species in order to test the generality of the new model of evolutionary change. A direct experimental confirmation of this model will help explain the origin of sexual dimorphism in all animals.
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2015 — 2017 |
Rice, Gavin Kopp, Artyom |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: the Molecular Basis of Convergent Innovations: Co-Option or Independent Origin of Regulatory Modules? @ University of California-Davis
Although the diversity of traits observed in nature can seem infinite, it still represents only a subset of possible traits. Furthermore, some traits have evolved repeatedly in distantly related species. Does repeated origin of certain traits reflect shared genetic constraints? The structure of gene networks that control development could favor the evolution of some traits while making the origin of other traits less likely. In order to determine the role of gene networks in shaping biological diversity, this study will identify and compare the molecular mechanisms that led to the independent origin of similar traits in two distantly related species. This research provides important insights into the translation of genotype to phenotype. The PIs propose novel mentoring in molecular techniques to high school and undergraduate students from underrepresented groups.
The proposed study investigates distantly related groups of fruit fly species, which have independently gained similar male-specific morphological structures. Previous work has shown that the gene doublesex (dsx) is important in the formation of these traits in both groups, and that specific changes in the DNA sequence of dsx correlate with the origin of one of these structures. This research will test whether evolutionary changes in the same or different DNA sequences are associated with the origin of the convergent structure in the other group. Answering this question will help determine the role of the genetic network encompassing dsx in the independent origin of similar traits in these two groups of species.
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2015 — 2017 |
Kopp, Artyom |
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. |
Evolutionary Turnover of Tissue-Specific Transcriptomes in Drosophila @ University of California At Davis
DESCRIPTION (provided by applicant): All cells in the body share the same genome yet assume different identities and perform different functions. The functional capacity of an organ depends on the composition of its transcriptome - the subset of genes that are actively expressed in that organ. In the course of evolution, transcriptome turnover - qualitative remodeling of tissue-specific transcriptomes through gains and losses of gene expression - can lead to major changes in organ function. This is particularly true in the male reproductive system, which shows the highest rate of evolutionary divergence in all animals including humans and their closest relatives. The overall goal of this project is to achieve a systematic understanding of the genomic mechanisms responsible for transcriptome turnover in the male reproductive system using a group of closely related Drosophila species as a model. These genomic mechanisms span the range from the origin of entirely new genes to the recruitment of old genes for novel functions. Our first aim is to quantify the rate at which each of these mechanisms contributes to transcriptome turnover, in order to understand the relative importance of each mechanism in shaping organ function. In addition, we will determine whether transcriptome turnover occurs at a steady rate, or is accelerated during the origin of particular species. Our second aim is to characterize the changes in genetic regulatory networks that result from the recruitment of new genes into the reproductive organs. To accomplish this, we will develop a new transgenic method for in vivo protein modification, and use this method to identify the downstream targets of the regulatory genes that were recruited into the male reproductive system recently in evolution. Our third aim is to understand how the introduction of new genes into the transcriptome affects organ function and, especially, male fertility. This will be accomplished by systematically knocking out recently recruited genes of different age specifically in the reproductive organs. Finally, we will use computational methods to understand how tissue-specific recruitment events influence the subsequent evolution of genes and genomes. Together, these approaches will help elucidate the evolutionary processes that influence male fertility and, more generally, the genomic mechanisms that promote complexity and diversity in animal evolution.
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2016 — 2018 |
Luecke, David (co-PI) [⬀] Kopp, Artyom |
N/AActivity Code Description: No activity code was retrieved: click on the grant title for more information |
Dissertation Research: the Evolutionary Recruitment of Effector Genes Into a Novel Sensory System @ University of California-Davis
The fruit fly Drosophila prolongata exhibits a unique set of sensory organs on the front legs. This study examines the genomics of their cells to learn how a group of genes is recruited to form a new specialized cell type. Distinct types of tissues and cells are differentiated by which genes are expressed. Cells produce their varied functions by turning the genes necessary for these roles on, while keeping other genes off. Errors in the expression of genes is one cause of developmental disorders and other diseases, yet the mechanisms of expression control are still not well understood. Observing the patterns of the recruitment process will illustrate how a new cell type evolves, how gene expression is controlled in different types of cells and tissue, and why expression control breaks down. This research will expand the training of a graduate student, who also leads public outreach activities at his university and provides research experiences for high school students and undergraduates.
To study the gene recruitment process, the evolutionary history of genes expressed in the novel sensory organs of Drosophila prolongata will be inferred. The mRNA from forelegs of this and several closely related species will be sequenced. The gene sequences present in the mRNA reflect which genes are expressed. These will be filtered based on similarity to sequences of known sensory genes; those present only in D. prolongata samples represent genes that have acquired new tissue specificity. These genes will be compared to related genes in other fly species, including the well-studied D. melanogaster, to determine what characteristics make genes more malleable to expression shifts. The evolutionary patterns reflect naturally occurring variation and suggest mechanisms of creating expression control, factors relevant to gene regulation in other organisms.
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2017 — 2020 |
Kopp, Artyom |
R35Activity Code Description: To provide long term support to an experienced investigator with an outstanding record of research productivity. This support is intended to encourage investigators to embark on long-term projects of unusual potential. |
Molecular Genetics of Evolutionary Innovations @ University of California At Davis
Project summary ?Evolutionary innovation? refers to the origin of entirely new traits, as opposed to the modification of existing traits. Although such novelties are relatively rare, all the complexity and diversity of life has ultimately been shaped by evolutionary innovations that occurred in a nested pattern, with every innovation dependent on many earlier novelties. Despite their critical importance for everything from geological nutrient cycles that support all life on Earth to human sentience that distinguishes us from our closest relatives, the molecular mechanisms of evolutionary innovations are understood far less than the evolution of existing traits. This is true at all levels of biological organization, from single molecules to the most complex features of animal form and function. We understand the evolution of existing organs and cell types better than the origin of new ones; quantitative variation in gene expression has been explored in much greater detail than the origin of novel regulatory pathways; much more is known about the evolution of existing genes than about the origin of new genes, and so on. It is this gap in our knowledge that motivates our work. To achieve a comprehensive understanding of evolutionary innovations, it is necessary to connect novelties at all levels of biological organization: from new functional elements in the genome, to new genetic pathways, to new morphological structures. Research in our lab will advance in three directions, using the Drosophila model system. First, we will identify the molecular mechanisms responsible for the origin of new morphological structures that evolved recently within Drosophila. We will identify the DNA sequences that gave rise to phenotypic innovations, and reconstruct the cell differentiation pathways than translate these changes into novel morphologies. Second, we will examine the genomic mechanisms that qualitatively remodel the gene expression profiles of different organs and cell types, and quantify the relative contributions of each type of genomic change to the turnover of genes expressed in each tissue. We will test whether the regulatory circuits that control gene expression evolve predominantly by incorporating individual genes, or by recruitment of larger genetic modules. Third, we will identify the molecular changes responsible for the origin of new regulatory elements that control gene expression from non-functional ancestral sequences. By focusing on novel regulatory elements that evolved within natural populations of a single species, we will reconstruct the series of mutations that create new functional elements in the genome, and elucidate the impact of these mutations on gene regulation. Together, these approaches will promote a deep mechanistic understanding of evolutionary innovations.
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