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Theme 2 Module 2 Script

Slide 1:
Intro slide. Theme 2, Module 2
Slide 2: YOUR SUMMARY NOTES:
Academic Property Statement
Slide 3:
McMaster University’s Land Acknowledgement

Slide 4:
Theme 2, Module 2- The genetic code

Slide 5:
In this module, we will:
 Determine the minimum number of
nucleotides that may code for a codon and
therefore a specific amino acid
 We will also examine classical experiments
that revealed the details of the genetic code
 In addition, we will identify the characteristic
features of the genetic code
 We will conclude the module, by considering
how the genetic code is able to be translated
into a polypeptide sequence that codes for a
specific protein sequence

Slide 6:
Unit 1: The Genetic code

Slide 7:
We have learned that the genetic information of a cell
is contained in the DNA and how transcription can
create a copy of the genetic sequence of a gene.
Transcription is an extremely valuable way of creating
multiple copies of the gene and it can be further
regulated by RNA stability or compartmentalization.
That said, we still have not made a protein. We have
not taken the transcribed nucleotide code and
translated it into another language - the language of
proteins.

Proteins are made from 20 different amino acids, but

there are only four nucleotides in mRNA: adenine (A),
cytosine (C), guanine (G), and uracil (U). How can
these four nucleotides code for all 20 amino acids?
That is, how does a mRNA molecule act as a template
for polypeptide synthesis? The manner in which
researchers were able to decipher the genetic code
that is contained in the DNA blueprint and that is
transcribed into mRNA is actually a very interesting
story.
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nucleotides, but this would be unnecessary and would

increase the redundancy in the code.

Slide 8:
Unit 2: Defining a codon
YOUR SUMMARY NOTES:
Slide 9:
Shortly after the discovery of the structure of DNA by
James Watson, Francis Crick and Rosalind Franklin,
researchers became eager to understand how to read
the hidden messages contained within DNA
molecules. Researchers understood that to be able to
crack the genetic code, it is important to determine
how many specific nucleotide bases code for a single
amino acid.

It was a physicist, named George Gamow, who

suggested the number of nucleotides that would be
necessary to code for one amino acid. In 1954, he
founded the RNA Tie Club. This club consisted of 20
members (one for each amino acid), and four
honourary members (one for each nucleotide in
nucleic acids). Gamow first reasoned that if one
nucleotide coded for one amino acid, then DNA could
only code for four distinct amino acid residues. This is
much less than the required 20 amino acids that cells
utilize and so he determined that a 1-base code
would not be enough to code for all 20 amino acids.

Slide 10:
Based on the same reasoning, Gamow rationalized
that a 2-base code would not be sufficient to code for
the 20 amino acids of the cell. If we consider that
there can be any of the four bases at each of two
positions, this would give us 4 × 4 = 16 combinations
or 16 distinct doublets. This is still not enough since
all of the possible doublets would only code for 16
amino acids.

Slide 11:
If three nucleotides (a triplet) were to make up the code
for each amino acid, we can see that there are 4 x 4 x 4 =
64 distinct combinations of three nucleotides. This is
more than we need, since we only need 20 distinct
codes, but it is the 3-base code is the smallest group of
nucleotides that will accommodate the need to code for
20 amino acids. This would mean that multiple unique
triplets would code for the same amino acid, a
redundancy in the code. More nucleotides could also
work; the code might be comprised of groups of 4 or 5
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triplet codon. As seen, UCA codes for serine, CAU

codes for histidine, AUC codes for isoleucine.

Slide 12:
Unit 3: Deciphering the code YOUR SUMMARY NOTES:

Slide 13:
To decipher how the mRNA code can be translated
into functional proteins, researchers needed to take
simple mRNA sequences and see what they coded
for. At the same time that the RNA Tie Club was
formed, two non-members, Marshall Nirenberg and
Johann Matthaei, used a cell-free system to decipher
the first letter of the code in 1961. Nirenberg and
Matthaei placed all the components that they
believed were necessary for protein synthesis into
tubes. This included an RNA template, nucleotides,
ribosomes, amino acids and an energy source. In
these experiments, they were able to determine what
specific amino acids a particular RNA nucleotide
template could give rise to. They started by making a
very simple nucleic acid made up of a string of uracils.
Nirenberg and Matthaei discovered that this simple
nucleic acid produced a repeated simple polypeptide
sequence that contained identical amino acids.
Specifically, repeated sequences of phenylalanine.
This was always translated into a string of
phenylalanine residues. But how many uracils coded
for a single phenylalanine? Was it one, two, more?

Slide 14:
Follow-up research used a nucleic acid with
alternating uracils and cytosines. It was found that
this strand of nucleotides was always translated into a
polypeptide string of alternating serine and leucine
amino acids. What does this suggest about the code?
What is a possible number of nucleotides that code
for a single amino acid? These results confirmed that
three nucleotides make up what is referred to as a
codon, that will code for a specific amino acid in a
protein.

Slide 15:
More simple mRNAs were constructed. In each case,
a novel sequence of 3 nucleotides seemed to code for
a distinct amino acid. These simple mRNAs were used
to determine the specific amino acid encoded in each
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Slide 19:
Much like methionine, the amino acid tryptophan is
only coded by one unique codon (UGG).

Slide 16:
Unit 4: The standard code YOUR SUMMARY NOTES:

Slide 17:
The standard genetic code is summarized in this
table. It is important to keep in mind that codons are
always written in a 5’ to 3’ direction. To read the
amino acid that is coded by any particular mRNA
codon from this table, the first position of the
nucleotide triplet is located on the left hand most
column of this table. From there, we can move
towards the right and select a specific box that
matches the nucleotide in the second position of the
mRNA triplet. Finally, the nucleotide in the third
position of the codon triplet is easily identifiable by
selecting from the options in the right-hand box that
matches the third position of the codon. The coded
amino acid is indicated by its three letter and single
letter representations.

This table represents the codons that can be encoded

in the mRNA transcript based on the four possible
nucleotide bases in mRNA. Interestingly, by replacing
the uracils with thymine, we are able to determine
the DNA nucleotides that were the sequence on the
non-template strand (or the codons on the coding
strand). The fact that the RNA transcript has the
same base-sequence as the non-template strand, is
what makes the non-template strand often referred
to as the coding strand. The non-template or coding
strand will contain the same codons as the mRNA
while the non-coding or template DNA strand
contains complementary anti-codons.

Slide 18:
There are many interesting observations about the
genetic code. One is that only the nucleotide triplet
AUG codes for methionine. This unique triplet is the
first triplet in every protein coding sequence. It is the
AUG start codon that signals the region where protein
synthesis should begin.
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mRNA and so is sometimes called the coding strand.

This allows researchers to predict the protein
sequence of a gene from the DNA sequence. We
know that translation starts at the AUG start codon.
By reading groups of 3 nucleotides, we can deduce
the codons and hence the amino acids of the protein.
This is referred to as the reading frame of a protein.
The entire continuous sequence of a gene that begins
at a triplet start codon code and ends with a triplet
stop codon code is commonly referred to as the open
reading frame.
Slide 20:
As suggested by the early predictions made by George YOUR SUMMARY NOTES:
Gamow, there is a great degree of redundancy in the
genetic code. This is demonstrated by the fact that
61 out of 64 possible nucleotide triplets are able to
code for the 20 amino acids of the cell. Redundancy
occurs because there are more unique triplets than
there are unique amino acids. One example is seen
here where four distinct triplets code for the same
amino acid, serine. Though the genetic code is
redundant, it is also unambiguous. This means that a
unique codon triplet will always code for a specific
amino acid and will never code for more than one
amino acid. This is essential as the cell has to produce
the correct proteins with the appropriate sequence,
structure, and functionality. The unambiguous
natures of the genetic code ensures that there will
never be any confusion as to which amino acid is
placed at each position on a growing polypeptide
chain.

Slide 21:
In addition, the genetic code contains three codons
that do not code for an amino acid at all. These
codons are generally found at the end of protein
coding sequences and signal that the translation of
mRNA into a polypeptide sequence is complete, and
therefore stopping the translation process. These are
referred to as translation stop codons.

Slide 22:
As we have learned, the process of transcription
involves reading genetic information from a DNA
template and synthesizing a complementary, or an
antiparallel RNA molecule. Because RNA polymerase
copies the DNA template strand, the sequence of the
template strand is the complement of the mRNA, and
so is often termed non-coding. This means if you read
the sequence of the DNA non-template strand, except
for the substitution of U for T, it is the same as the
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above, after the inserted G, the codons change from

ATA, TAC, and CAT to GAT, ATA, and CCA. While
transcription and translation will still occur, these
nucleotide triplets now code for different amino acids
in the polypeptide. A similar effect would happen if 1
nucleotide were removed. The researchers observed
the same effect when 2 nucleotides were added or
removed. These types of changes are referred to as
frameshift mutations. Interestingly, in the example
shown here, if a compensating nucleotide were
removed later in the code, the original reading frame
would be restored but the resulting protein would
have a section of wrong amino acids in the middle of
Slide 23: it, although the effect would be minimized.
Unit 5: Reading frames
YOUR SUMMARY NOTES:
Slide 24:
The coding region of a gene is the open reading
frame. Scanning DNA for these open reading frames
that begin with a start codon and end with a stop
codon is one way to look for genes along a DNA
sequence. A reading frame reflects the way in which
a nucleotide sequence is read. There are one of three
possible ways to read a nucleotide sequence.

Consider the hypothetical 15 nucleotide-long portion

of DNA illustrated in this figure. Once the template
strand is transcribed into mRNA, translation or
reading of the mRNA can occur from the first, second,
or third nucleotide. These are referred to as the first,
second, and third reading frames. As you can see, a
reading frame will affect the amino acids that make
up the sequence of a polypeptide, and ultimately, the
final protein that is produced. Note that, if nothing is
known about the genes on a particular DNA molecule,
there is the potential for each strand of the double
stranded DNA to be the template strand and
therefore you have six reading frames in total, three
reading frames in one direction and three in the
reverse direction on the opposite strand.

Slide 25:

In 1961, Francis Crick, Leslie Barnett, Sydney Brenner,

and Richard Watts-Tobin provided conclusive
evidence that the code was written out in triplets of
nucleotides. If a single nucleotide was added within
the nucleotide sequence, the code was misread. The
series of codons after the added nucleotide were
different from the original series. In the example
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necessary proteins. While the idea of an RNA world

hypothesis seems possible, its general acceptance as
the molecule responsible for the origin of life needs
further evidence.

Slide 30:
In this module, we have seen that:
 A codon is a triplet of nucleotides in a gene
or in the mRNA copy of a gene.
 The genetic code is redundant and
unambiguous.
 transfer RNAs are required to translate the
genetic code into a polypeptide sequence.

Slide 26:
When three nucleotides are removed as shown here,
there is no frameshift, that is no change in reading YOUR SUMMARY NOTES:
frame. Instead, a single triplet codon has been
removed and there is a corresponding removal of a
single amino acid in the polypeptide. All of the codon
sequences after the removal of the single codon are
conserved, maintaining the identity of most of the
protein. Similarly, adding a codon will simply add one
amino acid to the protein, but the reading frame of
the mRNA and most of the remainder of the
polypeptide sequence are conserved.

Slide 27:
Unit 6: RNA and the origins of life

Slide 28:
Today we think of DNA as the “blueprint of life”, but it
is RNA that turns that information into the
components that make up a cell. We know that it is
the transfer RNAs (tRNAs) that act as the
intermediate between the mRNA and the
polypeptide. They are the translators between the
two codes. The ribosome, containing ribosomal RNA
(rRNA), is the machinery that facilitates this process.
We are also aware of cases where RNA molecules are
able to serve as catalytic units (such as the small
nuclear RNAs of the spliceosome). So, while the
origin of RNA remains largely unclear, it is a subject of
much discussion and debate. The RNA world
hypothesis suggests that some type of ancestral RNA
molecule was the precursor to current life. This is
largely supported in the fact that RNA molecules play
such important roles in converting our genetic
information coded in DNA into functional and
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Theme 2 Module 2 Script