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Genes Control ... Development Physiology Behavior Infectious Disease Inherited Disease Technology DNA: Drosophila melanogaster WHY FLIES… 1) Great Genetics 2) Short life span 3) Small Size 4) Small (sequenced!) Genome Great Genetics!!! Protein Gene Biochemical Function Function Phenotype Red-Eyed and White-Eyed Fruit Flies Eye Color Production in Drosophila yellow ebony vestigial eyeless Curly Drosophila’s Contributions to Genetic Research • 1910 First mutation: white eyes (T. H. Morgan) • 1913 First genetic map showing genes arranged in a linear order (A. H. Sturtevant) • 1916 Proof that genes are located on chromosomes (C. B. Bridges) • 1927 X-rays cause mutations and chromosomal rearrangements (H. J. Muller) • 1934 First physical mapping of a mutation (T.S. Painter) • 1975 First physical mapping of a gene (D. S. Hogness) • 1980 First comprehensive analysis of mutants that affect animal development – (C. Nusslein-Volhard, E. Wieschaus, E. Lewis) Nobel Prizes Drosophila Life Cycle Homeotic Mutations: The conversion of one body part into another Haltere to wing transformation Developmental Genetics! Antennae Dominant, gain of function allele of the Antp gene conversion to legs! Cell Proliferation Control During Animal Development and its Relation to Cancer Cancer develops through gradual changes in cell morphology and properties Normal Carcinoma in situ Dysplasia Malignant carcinoma The Cell Cycle Progress Through The Cell Cycle is Regulated Cyclin Dependent Kinases (cdk) Control Progress Through The Cell Cycle cyclin B/cdk1 cyclin A/cdk1 cyclin D/cdk4 cyclin A/cdk2 cyclin E/cdk2 Gene Expression Regulates Cyclin Dependent Kinase Activity During the Cell Cycle (and vice versa) …. cyclin B/cdk1 cyclin A/cdk1 cyclin D/cdk4 cyclin A/cdk2 cyclin E/cdk2 Do Flies Get Cancer? YES! (Sort of…) St Johnston, Nat Rev Gen 3:176 (2002) Flies are like little humans with wings… http://superfly.ucsd.edu/homophila/ Genes involved in 74% of human diseases, including cancer, can be found in Drosophila The Cell Cycle What About Development? Drosophila Embryonic Cell Cycles: M S M G2 G1 S S Early Drosophila development occurs in a syncytium Nuclear Division Cycles t = 15 min t = 60 min t = 120 min GFP Labeled Chromosomes* gas permeable membrane cover slip *Courtesy of Rob Saint, University of Adelaide, Australia Mitosis in an Early Fruit Fly Embryo
