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Drosophila Melanogaster Genome And its developmental process
- 1. Drosophila Genome and itsLife Cycle SUBHRADEEP SARKAR M.Sc IN APPLIED GENETICS
- 2. A wild-type Drosophilamelanogaster, or fruit fly, has multifaceted brick red eyes, a tan thorax studded with arched black bristles, a striped abdomen, and a pair of translucent wings. The fly’s rapid life cycle, low chromosome number, small genome size, and giant salivary gland chromosomes are among the experimental advantages that made D. melanogaster the central organism in the study of transmission genetics in the first half of the twentieth century. These same features also made Drosophila a major model organism in genetic studies of animal development and behavior in the last quarter of the century.
- 3. Why is somuch attention paid to Drosophila genome?
- 4. 61 %human diseases have recognizable correspondence in genetic code of fruit fly 50 % of protein sequences have analogs with mammals Drosophila is used in genetic simulations of some human diseases, including Parkinson's disease, Alzheimer's sclerosis and disease of Hantington used for exploration of mechanisms laid in the basis of immunity, diabetes, cancer and narcotic dependence model system for the investigation of many developmental and cellular processes common to higher eukaryotes, including humans Drosophila and human development are homologous processes. Unlike humans, Drosophila is subject to easy genetic manipulation. As a result, most of what we know about the molecular basis of animal development has come from studies of model systems such as Drosophila.
- 5. Modern Drosophila geneticsoriginated with Thomas Hunt Morgan’s discovery of the sex-linked white eye mutation in 1910. The fountainhead of Drosophila genetics. Thomas Hunt Mor- gan and his students in the fly room at Columbia University, at a party in 1919. Morgan (back row, far left), Sturtevant (front row, third from the right), Calvin Bridges (back row, third from the right), and Herman J. Muller (back row, second from the left).
- 6. Giant polytene chromosomesof larval salivary gland are key tools Replicate 10-11 times 1024-2048 sister chromatids stay associated under perfect lateral register Homologous chromosome stay tightly synapsed Chromocenter – common region where centromeres coalesce Fig. 14.6a
- 7. Several characteristics ofDrosophila are useful for genetic analysis. a. The life cycle is relatively short, and each fly can produce thousands of progeny. b. A moderate amount of crossing-over occurs in females and no crossing-over occurs in males. c. Balancer chromosomes help preserve linkage. d. P-element transposons are tools of molecular manipulation useful for transformation, gene tagging, and enhancer trapping. e. Genetic mosaics resulting from mitotic recombination help track the roles of individual genes in the development of specific body structures. f. Ectopic expression can help pin down the function of a gene by making it possible to examine the effects of overexpressing the gene product or expressing the gene product in the wrong tissues.
- 8. Genetic regulation ofdevelopment in Drosophila: Fig. 19.18, Developmental stages of Drosophila (10-12 days) Egg ↓ Larva (3 instars) ↓ Pupa ↓ Adult ↓
- 9. Structure of theDrosophila Genome Chromosomes of Drosophila Four chromosomes designated 1-4 XY sex determination (XX females, XY males) Sex determined by X:A ratio
- 10. Structure and Organizationof the Drosophila Genome The Drosophila genome is about 5% the size of the human genome and is packaged in far fewer chromosomes. It contains roughly 13,600 genes, about a half of the number found in the human genome. This means that the density of genes on Drosophila chromosomes is higher than that of genes in the human genome. Even so, about one-third of the fly genome consists of repetitive sequences that do not encode proteins or that act as transposable elements.
- 11. Drosophila Genome The haploidgenome contains about 170,000 kb of DNA. Roughly 21% of this DNA consists of highly repetitive “satellite” DNA that is concentrated in the centromeric heterochromatin and the Y chromosome. Another 3% consists of repeated genes that encode rRNA, 5S RNA, and the histone proteins
- 12. Approximately 9% iscomposed of around 50 families of transposable elements, which are roughly 2–9 kb in length; the number of copies of each type of element varies from strain to strain but is usually somewhere between 10 and 100. In addition to residing at scattered sites within the euchromatin, many transposable elements are found in the centromeric heterochromatin, while some are concentrated in telomeres.
- 13. An unusual featureof Drosophila chromosomes is that the telomeres do not consist of simple repeats, such as the TTGGGG or TTAGGG repeats found at the ends of chromosomes in other well characterized organisms. Instead, it appears that the rapid jumping into the telomeric region of certain kinds of transposable elements maintains the telomeres. These insertions into the telomeric region of the transposable elements counter the chromosomal shortening that inevitably occurs during the replication of the ends of linear DNA molecules. The remaining 67% of the genome consists of unique DNA sequences that reside mostly in the euchromatic arms.
- 14. The Drosophila GenomeProject has already sequenced the euchromatic portion of the genome. Analysis of this sequence suggests that there are approximately 13,600 genes in the fly genome. A major remaining goal of the Drosophila Genome Project is to obtain information about the function of each of these genes. Large collections of transposon-induced mutations, as well as new techniques for targeted gene knockouts by homologous recombination and RNA intereference, should make the inactivation of each of these 13,600 genes possible in the near future
- 15. The development ofthe anterior-posterior (AP) axis in the fruit fly depends on the coordinated action of the segmentation genes, which divide the body into three head, three thoracic, and eight abdominal segments; and the homeotic genes, which assign a unique identity to each segment.
- 16. Embryonic development inDrosophila: • Development begins with fertilization. • Prior to fertilization, molecular gradients exist within the eggs. Polar cytoplasm occurs at the posterior end---example of maternal effect. • 2 nuclei fuse after fertilization to form a zygote. • 9 mitotic divisions occur without cell division, and after 7 divisions, some nuclei migrate to the polar cytoplasm (posterior) creating germ-line precursors. • Other nuclei migrate to the cell surface and form blastoderm precursor. • 4 more mitotic divisions occur and all nuclei are separated by cell membranes.
- 17. Subsequent development dependson two processes: Fig. 19.20, Adult segmentation reflect Embryo segmentation 1. Anterior-posterior and dorsal-ventral molecular gradients exist in the egg---mRNAs and proteins placed in egg by mother confer maternal effect. 1. Formation of (1) parasegments and (2)embryonic segments, which give rise to (3) adult segments.
- 18. Three major classesof genes control development and differentation *Mutations identified by presence lethal or abnormal structures during development. 1. Maternal effect genes 1. Segmentation genes 1. Homeotic genes
- 19. The four classesof segmentation genes are expressed in the order maternal, gap, pair-rule, and segment polarity. The maternal genes produce gradients of morphogens. The gap genes, the first zygotic segmentation genes, are expressed in broad zones along the anterior-posterior axis. The pair-rule genes subdivide those broad areas into units that span two of the ultimate body segments. The segment polarity genes subdivide the two-segment units into individual segments. In the hierarchy of segmentation gene expression, each gene class is controlled by classes of genes higher in the hierarchy or by members of the same class.
- 20. 1. Maternal effectgenes Expressed by the mother during egg production; they control polarity of the egg and the thus embryo. bicoid gene • Regulates formation of anterior structures (mutants possess posterior structures at each end). • Gene is transcribed during egg production, and expressed after fertilization. nanos gene • Regulates abdomen formation (mRNAs collect in posterior of the egg). torso gene • Transcription and translation occur during egg production. • Occurs throughout the eggs, but is only active at the poles.
- 21. Fig. 19.24 Distribution ofbicoid mRNA and protein in the egg A = Anterior P = Posterior
- 22. 2. Segmentation genes: Determinethe segments of the embryo and adult, and thus divide the embryo into regions that correspond to the adult segmentation patterns. 1. Gap genes Subdivide the embryo along the anterior-posterior axis. Mutation results in the deletion of several adjacent segments. 1. Pair rule genes Divide the the embryo into regions, each containing parasegments. Mutations cause deletions of the same part of a pattern in every other segment. 1. Segment polarity genes Determine regions that become segments of larvae and adults Mutants possess parts of segments replaced by mirror images of adjacent half segments.
- 23. Fig. 19.25, Functionsfor segmentation genes defined by mutations.
- 24. The homeotic genesare master regulators of other genes that control the development of segment-specific structures. The homeobox in each homeotic gene encodes a homeodomain that allows the gene products to bind to specific target genes and control their expression. The homeotic genes are, in turn, regulated by the earlier acting gap, pair-rule, and segment polarity genes. Homeotic mutations cause particular segments, or parts of them, to develop as if they were located elsewhere in the body. Most homeotic mutations map to the bithorax and the Antennapedia complexes.
- 25. 3. Homeotic genes: •Homeotic genes specify the body part to develop at each segment. • Adult body parts develop from undifferentiated larval tissues called imaginal discs. • Homeotic mutants develop a different body part at a particular segment (imaginal disc) than the usual body part. • Different homeotic gene groups share similar sequences of ~180 bp called homeoboxes that code proteins. • Homeoboxes regulate development and produce proteins that bind upstream of the gene units. • Homeotic gene complexes are abbreviated Hox. • Hox genes also specify body plans in vertebrates and plants.
- 26. Fig. 19.26 Examples ofhomeotic Drosophila mutant with the bithorax mutation What is wrong with one of these flies?
- 27. The finding ofhomeobox genes in other organisms such as the mouse has made it possible to identify developmentally important genes shared by all animals, demonstrating the evolutionary conservation of gene function.
- 28. Fig. 19.28, Organization ofbithorax homeotic genes in a 300kb region of the Drosophila genome. T = thoracic A = abdominal