Download Molecular Genetics

Molecular Genetics
1.
Introduction
a.
We have studied “classical” or “Mendelian” genetics up to this point. - It leaves a lot of
questions unanswered.
i. . What really is a gene?
ii.
How do different alleles actually differ?
iii. Is there a “genetic code” and how is it decoded to make an organism?
b.
Now we will answer these questions
i. They were answered in a series of experiments done through the 1930's to
1950's
c.
2.
The big question is how can living things make so many different proteins
Concept of Gene
a.
Coined by W. Johannsen in 1909 - referred to hereditary factors of Mendel
i. Indivisible units on chromosomes
ii. Really not so indivisible now
iii. Genes carry the code to make an organism
b.
One Gene One Enzyme hypothesis
i. Beadle and Tatum
1.
Studied the mold Neurospora crassa
2.
Created mutants using radiation
3.
Found each mutant was defective in only 1 enzyme
4.
Concluded that one gene produces one enzymge
ii. New definition of gene - a nucleic acid sequence that encodes a functional
polypeptide or RNA sequence
c.
DNA
i. Made of repeated units called nucleotides
1.
sugar
2.
nitrogenous base
a.
Adenine
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Molecular Genetics
b.
Thymine
c.
Guanine
d.
Cytosine
ii. Watson and Crick found that DNA is a double helix
1.
Like a spiral staircase
a.
Bases are steps
b.
Sugars are railings
c.
Bases match with one another - hydrogen bonds between each
i. A-T
ii. G-C
d.
Thus they are anti-parallel
i. 5' end on one is matched with 3' end of other
e.
Complementary
i. If you know the sequence on one strand - you can tell
the sequence on the other
1.
Remember the chromatids?
2.
Each time a cell divides the old strand is a
template for a new strand
2.
How does DNA code for a protein?
a.
4 bases -20 amino acids
b.
Codon
i. 3 bases in a row that specify a particular amino acid
1.
It turns out that many amino acids have
more than 1 codon
2.
3.
There are also stop codons
How does system code for a protein
a.
Codons are organized in a line - just like amino acids on a
protein
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Molecular Genetics
b.
Transcription
i. Base pair sequence is transcribed onto messenger
RNA (mRNA)
1.
RNA is like DNA
a.
It is single stranded
b.
Uracil replaces thymine
c.
RNA polymerase makes a
complementary copy of the DNA
d.
e.
A-T-G-C-T-A-C-T
DNA
U-A-C-G-A-U-G-U
mRNA
Only 1 strand of DNA is used
i. Called the Coding Strand'
c.
Translation
i. mRNA goes out into cytoplasm and attaches to
ribosome
ii. A bunch of ribosomes line up on mRNA
iii. There are 20 transfer RNA's in the cytoplasm of the
cell
1.
These are shaped like a cloverleaf
a.
One end attaches to a specific
amino acid
b.
The other end is an anticodom that
is the exact opposite match for a
particular codom
c.
The tRNA attached briefly to the
mRNA on the ribosome and brings
in a particular amino acid at just the
right place in the protein chain
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Molecular Genetics
2.
4.
2.
Thus exactly the right protein gets made
Regulation of gene expression
a.
Very necessary
b.
Development of embryo
c.
Timing of events in life of organism
d.
Won't talk about it
Recombinant DNA
a.
It turns out that DNA is very durable and can be manipulated
i. Restriction endonucleases - scissors
ii. Ligaases - paste
iii. Allow us to manipulate DNA
1.
Make our own genes
2.
Transfer genes from one organism to another
a.
Splice genes into bacteria so that they make chemicals that we
want
b.
b.
Natural pesticides in plants - BT cotton
Polymerase chain reaction
i. Allows us to amplify DNA
ii. Copy from small amount
1.
Forensic science
a.
DNA is unique for an individual
b.
If you can sequence DNA, you can identify the individual
i. DNA fingerprinting
c.
Genomics
i. If we knew the sequence of DNA in a representative human we could determine
the genes to make a human
1.
Important in detecting errors - mutations
2.
Human DNA has been sequenced - at Wash U in St. Louis
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Molecular Genetics
a.
3.
d.
Some of our graduates helped
Tests to detect cystic fibrosis or Huntington's chorea
Molecular genetics of cancer
i. Neoplastic growth - tumors
ii. Cancer caused by mutation of oncogenes
1.
Normal form is proto-oncogenes
iii. Complex system to control cell division
1.
Conversion from proto-oncogene to oncogene breaks down this system
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