1. Lecture 2 Topic 1

2. Genes, Chromosomes, and Genomes
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?
Prokaryotic cell?

3. Genes are Information Specific gene product
Specific time, place, and amount

4. Major Component Parts of Genes
Which part is responsible for what information?
Transcribed region
Transcribed region

5. Fruit fly: Common and Small
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

6. 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

7. 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??

8. 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
Radioactively labelled DNA but not
Protein enters bacterium on infection
R type transformed into S type

9. What is the chemical nature/structure of a Gene?
…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…
“I knew it
was a helix!”
“Good thing I snuck
a peak at Rosalind’s X-ray data”

10. 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]

11. Watson-Crick Base Pairs
Anti-parallel strands 5’ 3’ 3’ 5’

12. 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

13. 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

14. 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

15. 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

16. Genes, Chromosomes, and Genomes
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?
Prokaryotic cell?

17. 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?)