1. Chapter 14 From DNA to Proteins
Honors Biology Program
Mountain Pointe High School

2. What are the byssus of a mussels? Why are these byssus so important?

3. Archibald Garrod
First to notice that many heritable diseases were related to metabolic pathway malfunctions.
STEPS OF A METABOLIC PATHWAY:
Action of enzyme 1
Action of enzyme 2
Garrod hypothesized that each of his affected patients had inherited a single metabolic defect that interfered with an enzyme in a particular metabolic pathway.
Something has interfered with the action of enzyme 3. X A B C D
Completion of the pathway is blocked, and C accumulates.

4. Neurospora crassa and other fungal species
Beadle & Tatum
33 years after Garrod’s hypothesis, these scientists were experimenting with a common bread mold that’s capable of synthesizing everything it needs to survive except for a few basic substances.
They discovered that some of the fungal strains would only grow when supplied with vitamin B6, others would only grow in the presence of B12, etc.
Neurospora crassa and other fungal species

5. Beadle & Tatum
After careful examination, they discovered that there was a different defective enzyme in each mutant strain of the fungus.
In other words, each strain of fungus possessed an inherited mutation that corresponded to a defective enzyme.
This evidence supported Garrod’s “one gene, one enzyme” hypothesis!

6. Sickle-cell Anemia
The most common lethal genetic disease in African Americans, it causes normal red blood cells to become sickle shaped, which causes an incredible variety of health problems for its victims.
Normal red blood cell
Sickled red blood cell

7. Sickle-cell Anemia
It was discovered that this disease was caused by a defect in a protein known as hemoglobin that is found in red blood cells.
Normal hemoglobin is designated HbA.
Abnormal hemoglobin is designated HbS.

8. glass tube or plates containing gel
Pauling & Itano
upper buffer solution
movement of proteins
In 1949, these scientists subjected molecules of HbA and HbS to gel electrophoresis.
In this procedure, an electric field is used to move molecules through a gel.
Molecules are separated by their size, shape & surface charge.
electrode
glass tube or plates containing gel
gel
lower buffer solution
electrode
power supply

9. HbS molecules moved much slower.
Pauling & Itano
HbA molecules carried the greatest surface charge and therefore moved through the gel the fastest.
HbS molecules moved much slower.
As molecules move through the gel, they’re separated into distinct bands.

10. Vernon Ingram
Pinpointed the biochemical difference between HbA and HbS
Hemoglobin (left) is a molecule made of 4 polypeptide chains, 2 alpha & 2 beta.
Ingram discovered that the defect was caused by an incorrect amino acid substitution in one of the beta chains!

11. Beta chain of an HbA molecule Beta chain of an HbS molecule
```
Hemoglobin molecule
Beta chain of an HbA molecule
VALINE
PROLINE
THREONINE
LEUCINE
GLUTAMATE
HISTIDINE
GLUTAMATE
Beta chain of an HbS molecule
A beta chain
PROLINE
VALINE
VALINE
THREONINE
GLUTAMATE
HISTIDINE
LEUCINE

12. The discovery of the difference between the alpha & beta chains of hemoglobin meant that…
Two genes must code for hemoglobin, one for each type of polypeptide chain.
Genes code for all proteins, not just enzymes.
The amino acid sequences of polypeptide chains are encoded in genes.

13. 3 Different Types of RNA

14. The Three Types of RNA
mRNA is a single-stranded molecule that takes DNA’s protein-building instructions out of the nucleus.
rRNA is the primary component of ribosomes, the organelles that actually make proteins.
tRNA is the molecule responsible for delivering amino acids one by one to a ribosome in the correct order specified by the mRNA molecule.
A messenger RNA molecule (mRNA)
A ribosomal RNA molecule (rRNA)
A transfer RNA molecule (tRNA)

15. Comparing DNA and RNA Double-stranded Deoxyribose sugars
4 nitrogenous bases
Adenine
Cytosine
Guanine
Thymine
Single-stranded
Ribose sugars
4 nitrogenous bases
Adenine
Cytosine
Guanine
Uracil
Like thymine, uracil (at right, in blue) is a pyrimidine and is capable of pairing with adenine.

16. transcribed DNA winds up again
Transcription
sugar-phosphate backbone of one strand
of nucleotides in a DNA double helix
sugar-phosphate backbone of
the other strand of nucleotides
part of the sequence of
base pairs in DNA
Transcription is the process of using a portion of the DNA molecule as a template to assemble a molecule of mRNA.
Only a selected stretch of one DNA strand is used as a template.
Transcription is initiated at a promoter, a DNA base sequence that signals the start of a gene.
transcribed DNA winds up again
DNA to be transcribed unwinds
Newly forming RNA transcript
The DNA template at the assembly site

17. Transcription
growing mRNA transcript 3’ 5’ 3’ 5’
direction of transcription 3’ 5’
A “pre mRNA” strand
Once the enzyme DNA helicase has unzipped the DNA molecule at the appropriate location…
RNA polymerase adds the required complementary bases to the exposed bases on one of the DNA strands.

18. Transcription Next, the pre- mRNA molecule must be modified.
unit of transcription in a DNA strand
Next, the pre- mRNA molecule must be modified.
A nucleotide known as a “cap” is attached to the 5` end.
A nucleotide known as a “poly-A tail” is attached to the 3` end. 3’ 5’
exon
intron
exon
intron
exon
transcription into pre-mRNA
poly-A
tail
cap
(snipped out) 5’
(snipped out) 3’ 5’ 3’
mature mRNA transcript
Before the mRNA transcript is finished, useless sections known as introns must be snipped out, leaving only exons remaining.

19. Now that the mRNA has been transcribed, what does its message mean?
The Genetic Code
DNA template
codon
codon
codon
codon
codon
mRNA transcript
Amino acid?
Amino acid?
Amino acid?
Amino acid?
Amino acid?

20. amino acid attachment site
tRNA molecules have a nucleotide triplet known as an “anticodon” on one end and an attachment site for an amino acid on the other end.
anticodon
codon in mRNA
anticodon
tRNA MOLECULE
amino acid
attachment site
amino
acid
amino acid attachment site

21. platform for chain assembly
Ribosomes are composed of two subunits made of rRNA. These subunits are created in the nucleolus, travel separately out of the nucleus and only unite when mRNA messages need to be translated into proteins.
platform for chain assembly
tunnel
Small ribosomal subunit
Large ribosomal subunit
Complete ribosome

22. Translation 3 Stages of Translation: Initiation
tRNA molecule is attached to small ribosomal subunit.
mRNA molecule’s START codon (AUG) matches up with tRNA anticodon, attaches to small ribosomal subunit.
Large ribosomal subunit attaches to small subunit.

23. P (first binding site for tRNA)
Binding site for mRNA
P (first binding site for tRNA) A
(second binding site for tRNA)

24. Translation Next is the elongation stage:
Ribosome complex moves along mRNA molecule.
One by one, tRNA molecules deliver the amino acids coded for by the mRNA to A site.
Amino acids are linked together by peptide bonds, tRNA molecules exit P site of ribosome.

25. Translation The final stage is termination.
Ribosomal complex reads STOP codon on mRNA molecule.
No tRNA has an anticodon that corresponds to a STOP codon.
Proteins called release factors bind to ribosome, cause enzymes to detach mRNA & polypeptide chain from ribosome.
Ribosomal subunits separate.

27. Unwinding of gene regions of a DNA molecule
TRANSCRIPTION
Pre mRNA Transcript Processing
mRNA
rRNA
tRNA
Mature mRNA transcripts
Ribosomal subunits
Mature tRNA
TRANSLATION
Cytoplasmic pools of amino acids, tRNAs, and ribosomal subunits
Synthesis of a polypeptide chain at binding sites for mRNA and tRNA on the surface of an intact ribosome
FINAL PROTEIN
Destined for use in cell or for transport

28. Mutations
Changes in the nucleotide sequence of genes are known as mutations.
The most common types of gene mutations are:
Base-pair substitutions (shown at left)
Frameshifts
Insertions
Deletions
original
base triplet
in a DNA
strand
a base
substitution
within the
triplet (red)
As DNA is replicated, proofreading
enzymes detect the mistake and
make a substitution for it:
POSSIBLE OUTCOMES: OR
One DNA molecule
carries the original,
unmutated sequence
The other DNA
molecule carries
a gene mutation
Remember sickle-cell anemia?
It’s caused by a base-pair substitution that replaces the amino acid glutamine with valine.
VALINE

29. Mutations
mRNA TRANSCRIPT
DNA TEMPLATE
ARGININE
GLYCINE
TYROSINE
TRYPTOPHAN
ASPARAGINE
RESULTING AMINO ACID SEQUENCE
ALTERED mRNA MESSAGE
A BASE INSERTION (RED) IN DNA
ARGININE
GLYCINE
LEUCINE
LEUCINE
GLUTAMATE
ALTERED AMINO ACID SEQUENCE
The example above is a frameshift mutation known as an insertion.
This mutation causes DNA’s message to shift one base to the right.
A deletion would cause a one-base shift to the left.