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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