Artyom Kopp
University Of California Davis
Project start date: 2009-03-09
Project end date: 2013-01-31
Sponsored Links Excellgen http://Excellgen.com
GENETIC AND DEVELOPMENTAL MECHANISMS OF EVOLUTIONARY INNOVATIONS
Artyom Kopp, Assistant Professor
University Of California Davis, Office Of Research - Sponsored Programs, Davis, Ca 95618
Grant 5R01GM082843-02 from National Institute Of General Medical Sciences
Abstract: 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. 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
Keywords: 21+ years old; Adult; Affect; Affinity; Animals; Assay; Behavior; Behavioral; Binding Sites; Bioassay; Biochemical Genetics; Biologic Assays; Biological; Biological Assay; Biological Models; Body Tissues; Candidate Disease Gene; Candidate Gene; Cell Differentiation; Cell Differentiation process; Chimp; Chimpanzee; Chromosome Mapping; Comb animal structure; Combining Site; Combs; Crosses, Genetic; DNA; DNA Alteration; DNA Sequence; DNA mutation; Data; Deoxyribonucleic Acid; Development; Drosophila; Drosophila genus; Drug Design; Evolution; Experimental Models; Experimental Models, Other; Expression Profiling; Expression Signature; Female; Fruit Fly, Drosophila; Gene Action Regulation; Gene Alteration; Gene Expression; Gene Expression Regulation; Gene Localization; Gene Mapping; Gene Mapping, Total Human and Non-Human; Gene Mutation; Gene Regulation; Gene Regulation Process; Genes; Genetic Alteration; Genetic Change; Genetic Crosses; Genetic Differentiation; Genetic Divergence; Genetic Drift; Genetic defect; Genetic mutation; Genetic, Biochemical; Genetics, Gene Mapping; Genetics, Population; Genome; Genomics; Goals; Human; Human, Adult; Human, General; Lead; Link; Linkage Mapping; Mammals, Primates; Man (Taxonomy); Man, Modern; Model System; Modeling; Models, Biologic; Models, Experimental; Molecular; Molecular Fingerprinting; Molecular Genetic; Molecular Genetics; Molecular Profiling; Morphology; Motivation; Mutation; Natural Selections; Nucleic Acid Regulatory Sequences; Organ; Output; Pan; Pan Genus; Pan Species; Pathway interactions; Pb element; Phenotype; Phylogenetic Analysis; Phylogenetics; Physiologic; Physiological; Population; Population Genetics; Prevention Measures; Primates; Programs (PT); Programs [Publication Type]; Prophylactic treatment; Prophylaxis; Reactive Site; Regulator Regions, Nucleic Acid; Regulatory Pathway; Regulatory Regions; Regulatory Regions, Nucleic Acid (Genetics); Regulatory Sequences, Nucleic Acid; Research; Resolution; Selections, Natural; Sequence Alteration; Sexual Development; Shapes; Site; Structure; Testing; Tissues; Transgenic Organisms; Translating; Translatings; adult human (21+); comparative; developmental genetics; fruit fly; genetic mapping; genetic regulatory element; genome mutation; heavy metal Pb; heavy metal lead; innovate; innovation; innovative; language translation; male; molecuar profile; molecular signature; neurobiological mechanism; novel; pathway; programs; sensory system; sex; sex development; systems research; trait; transcription factor; transgenic
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
Project start date: 2009-03-09
Project end date: 2013-01-31
Budget start date: 1-FEB-2010
Budget end date: 31-JAN-2011
PFA/PA: PA-07-070
5R01GM082843-02 (2010): $259014
Grants awarded to Artyom Kopp
Genetic And Developmental Mechanisms Of Evolutionary Innovations
Artyom Kopp
Evolution And Ecologyuniversity Of California Davis
Grant 1R01GM082843-01A2 from National Institute Of General Medical Sciences IRG: GVE
Abstract: 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. 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
Project start date: 2009-03-09
Project end date: 2013-01-31
3R01GM082843-01A2S1 (2009): $164290