Download gene control regions?

Lecture 2 Topic 1
Genes, Chromosomes, and Genomes
Prokaryotic cell?
What’s a
Gene?
What are the
component
parts of a
gene?
What is the
chemical
structure of a
gene?
How does that
structure
provide for
function?
Genes are
• Information
– Specific gene product
– Specific time, place, and amount
Major Component Parts of Genes
Transcribed region
Transcribed region
Which part is
responsible
for what
information?
Introns: where do you find them, what advantage do they
offer, are they coming or going?
Yeast:
Rare and Small
Fruit fly:
Common and
Small
Humans:
Common and Large
• Introns in prokaryotic and organelle genes exits
but are rare
• Allow for making new proteins
•
alternative splicing…
•
recombining exons…
• Intron Early vs Intron Late hypotheses…
•
- HD gene in humans vs puffer fish
Comparison of Huntington Disease
Gene (HD) in Humans and Puffer Fish
Introns Evolution: Early vs Late? Getting Bigger or Getting Smaller?
Both genes have identical
Patterns of introns (66)
-Illustrate…
-Common ancestor
-If not early, at least they’ve
been around for a while…
Human HD = 180,000 bps
F. Rubripes HD = 24,000 bps
-Difference due to intron size
Difference in intron size…
-Repetitive DNA content
-Transposons…
Common ancester intron size??
What is the chemical
nature/structure of a Gene?
•
•
•
Gene = transforming principle
identified by Griffith
Transforming principle = DNA shown
by Avery, MacLeod and McCarty
DNA genetic material of bacterial
phage shown by Hershey and Chase
R type transformed into S type
Radioactively labelled DNA but not
Protein enters bacterium on infection
What is the chemical
nature/structure of a Gene?
“I knew it
was a helix!”
“Good thing I snuck
a peak at Rosalind’s
X-ray data”
…Didn’t know how
many strands,
orientation of the
strands, how to fit
the bulky bases into
the middle of a 20
angstrom helix, the
pitch of the helix,
how the structure
could provide a
mechanism for
specificity…
What is the chemical
nature/structure of a Gene?
Chargaff’s rules:
Base content of DNA
from different organisms
differs
-Not 1:1:1:1
-Specificity is possible!
-[A] = [T]
-[G] = [C]
-[purine] = [pyrimidine]
Watson-Crick Base Pairs
5’
3’
Anti-parallel strands
3’
5’
How does the structure provide for
function
2 strands
Anti-parallel
Right-handed
3.4 Angstroms
34 Angstroms
Bases parallel
Two grooves:
-minor
-major
Any sequence is possible: specificity for genetic information
Base pairing provides for replication, transcription
Grooves provide access for proteins to make sequence-specific contacts
Human Gene Example: Duchenne
Muscular Dystrophy and the DMD Gene
General Information
Heritable Genetic Disease
Dystrophy = muscle atrophy
Most famous of congenital muscular dystrophies
1 in ~5000 live births
Molecular Genetics
Defects in Dystrophin Gene (DMD) and Protein
(Dystrophin)
X-linked recessive disorder
Gene position Xp21
Major Phenotypic Features
Age of onset: Childhood
Muscle weakness
Calf hypertrophy
Elevated serum creatine kinase levels
Death from respiratory/cardiac failure by age 20
Mutations in DMD
Gene = 2.5 Mb
(gene control regions?)
85 exons:
mean exon size 0.2kb
mean intron size 35 kb
mRNA = 14kb
central exons are ~ identical
code for helical rod domain
Most common mutation:
= deletions
involving repetitive DNA
Dystrophin Function
Connection of the
extracellular matrix (ECM)
to the cell cortex of muscle
and non-muscle cells
ECM – Cell cortex
association important for cell
strength
Loss of Dystrophin makes
cells fragile
Muscle cell and muscle fibers
degenerate
Genes, Chromosomes, and Genomes
Prokaryotic cell?
What’s a
chromosome?
What types of DNA
sequences are in
chromosome?
How are the genes
of a chromosome
arranged?
What is the
structure of a
chromosome and
how does that
relate to function?
What’s a Chromosome
•
•
Chromosome = “coloured bodies” of the nucleus
Linear or circular DNA + protein (what about viruses?)
– One continuous DNA molecule
• Loops on mitotic chromosomes
• Pulses Field Gradient Electrophoresis
– Chromatin: Euchromatin and Heterochromatin
•
•
Contain linear arrangement of genes
Contain information for their own replication and segregation
–
–
–
•
Sometimes contain repetitive DNA
–
–
•
Duplicate and Segregate properly at during each cell/organelle division
– As opposed to plasmid or other extra-chromosomal elements (what about viruses?)