Drosophila melanogaster has been extensively studied for over a century as a model organism for genetic investigations

1. Drosophila : Model Organism

2. Introduction
 Drosophila melanogaster has been extensively studied
for over a century as a model organism for genetic
investigations
 many similar features and pathways with humans.
 It turns out that approximately 60% of a group of readily
identified genes that are mutated, amplified, or deleted in
a diverse set of human diseases have a counterpart
in Drosophila
 The fruit fly has many practical features that allow
scientists to carry out research with ease : A short life
cycle,
 ease of culture and maintenance, and
 a low number of chromosomes
 a small genome size (in terms of base pairs), but

3.  . Thomas Hunt Morgan (1866-1945)
developed Drosophila as a model system in
1909. Morgan, along with his students, Calvin
Bridges, Alfred Sturtevant, and Hermann Muller,
made some of the most important discoveries in
genetics through their work with Drosophila.
 Among these were the –
- genetic explanation of sex linkage (the location
of a gene on a sex chromosome);
- proof that genes are contained on
chromosomes;
- the demonstration that genes are arranged on a
chromosome in a linear order with fixed,
measurable distances between them, the

4. The Life Cycle of Drosophila
 The female fruit fly, about 3 mm in length, will lay
between 750 and 1,500 eggs in her lifetime.
 The life cycle - about 12 days to complete at room
temperature (25°C).
 After the egg (at a mere half a millimeter in length) is
fertilized, the embryo emerges in ~24 hours.
 The embryo undergoes successive molts to become
the first, second, and third instar larva.
 The larval stages are characterized by consumption
of food and resulting growth, followed by the
quiescent pupal stage, during which metamorphosis
followed by the emergence of the adult fly.

5.  Scientists can collect and harvest hundreds of grams
of embryos, larvae, or adults at a time. The material
can be frozen in liquid nitrogen, and then used as
the starting
point for preparing enzymes
such as RNA polymerase II,
or for purifying chromosomal
proteins such as the histones,
or for analysis of chromatin
structure.

6. Genetic information
 a complex of DNA plus specialized proteins
(histones) packed in the cell's nucleus.
 the fruit fly has only four: a pair of sex
chromosomes (two X chromosomes for females,
one X and one Y for males), together designated
Chromosome 1, along with three pairs
of autosomes (non-sex chromosomes)
 Chromosome 4 is the smallest and is also called
the dot chromosome

7.  Red eyes are normal in "wild-type" Drosophila
 mutant strain of flies that had white eyes, and, using
that difference in phenotype as a jumping-off point,
conducted an elegant series of experiments that
ultimately led to fundamental discoveries about the
physical basis of heredity in the bodies we call
chromosomes.

8. Drosophila as a model organism:
 In terms of base pairs, the fly genome is only
around 5% of the size of the human genome -- that
is, 132 million base pairs for the fly, compared with
3.2 billion base pairs for the human.
 In terms of the number of genes,, however, the
comparison isn't nearly so lopsided: The fly has
approximately 15,500 genes on its four
chromosomes, whereas humans have about 22,000
genes among their 23 chromosomes. Thus the
density of genes per chromosome
in Drosophila is higher than for the human genome.
 Humans and flies have retained the same genes
from their common ancestor (known as homologs)
over about 60% of their genome.
 Based on an initial comparison, approximately 60%
of genes associated with human cancers and

9. Dosage compensation
 A mechanism to equalize the dosage of X-
chromosome gene products by means of inactivating
one of female X-chromosomes in mammals. In
Drosophila dosage Compensation accomplished by
two fold transcriptional upregulation male X
chromosome.
 Dosage compensation in Drosophila increases the
transcription of genes on the single X chromosome
in males to equal that of both X chromosomes in
females.
 Site-specific histone acetylation by the male-specific
lethal (MSL) complex is thought to play a
fundamental role in the increased transcriptional
output of the male X.

10.  In Drosophila, like in humans, male cells have a
single X chromosome, while female cells have two.
Researchers have long debated over how X and
autosomal chromosome gene expression is
equalized between the sexes (generally regarding
two different models, known as the activation model
and the inverse model).
 The male-specific-lethal (MSL) complex functions as
a male-specific regulatory protein complex that
controls gene expression in male fruit fly cells.
 The activation model proposes that MSL upregulates
the transcription of X-linked genes twofold in male
cells.
 The inverse dosage effect model proposes that MSL
represses male autosomal gene expression to

11. MOLECULAR MECHANISMS OF X
INACTIVATION
 Blocking factores are released, Xist RNA is
stablized and upregulated.
 Before inactivation the X chromosome coated
with stabilized Xist RNA.
 Genes on the X chromosome are silenced
following Xist RNA coating using an unknown
mechanism.
 Chromatin modifications, including histone
deacetylation and methylation of promoters of
X- linked.

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