Bio 12 – DNA and Protein Synthesis

DNA and Protein Synthesis - “Life is a Three Letter Word!”

Functions of DNA →
1. Controls cellular activities
o carries a CODE
o Genetic instructions encoded in the sequence of bases strung
together
2. Replicates
o makes exact copies of itself to pass onto other cells
3. Mutates and recombines
o Source of the diversity and unity of life
o In sexual reproduction, DNA from male and female together
become the genetic information of offspring
o Mutations and recombinations of DNA allow for evolution
▪ First life forms thought to be self-replicating strands of
RNA

Structure of Nucleic Acids and DNA – A Review

N
N
P N
N

DNA & RNA are linear polymers of nucleotides

Each nucleotide is composed of a:

1. pentose sugar
2. phosphate
3. nitrogenous base

Two types of bases:

i) PURINES - have a double ring structure (adenine & guanine)
NH2 O
N N H
N N
H H
O N H O N
5' N 5' N NH2
O- P O CH2 O O- P O CH2 O
O- H H O- H H
H H H H

OH H 3'
OH H
3'

nucleotide: base = Adenine nucleotide: base = Guanine

ii) PYRIMIDINES - have a single ring structure (thymine, cytosine, uracil)

C22OH1S.DOC
 H NH2
H3C O H O

H N
2 H N H
H N H
2 O N 2
5' N
O N O O
5' O- P O CH2 O
5'
O
O- P O CH2
O O- P O CH2 O
O O- H H
O- H H H H O- H H
H H H H

3'
OH H
OH H 3' OH OH
nucleotide: base = Cytosine
3'

nucleotide: base = Thymine nucleotide: base = Uracil

RNA ONLY

Structure of DNA
• Nucleotides linked together to form double helix P
• Backbone of alternating molecules of deoxyribose and phosphate with a
nitrogenous base attached to each deoxyribose unit.
• Pairs of joined bases project inward, forming the rungs of the ladder P

• Bases are linked to each other by hydrogen bonds in a very strict pattern 
always a purine with a pyrimidine. P
P

There is COMPLEMENTARY BASE PAIRING BETWEEN STRANDS P

• ADENINE (A) bonds with THYMINE (T)

• GUANINE (G) binds with CYTOSINE (C) P

5' 3'
A T G T G A T C C A C G C G T

3' 5'

Paired strands of DNA run in opposite directions

• DNA replication and transcription must occur in the 5’ to 3’ direction – like how words must always be read from
left to right!

Genes → units of inheritance that control particular characteristics or capabilities of

an organism
• Segments of DNA within chromosomes
• Control cellular chemical reactions by directing the formation of enzymes.

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 DNA Replication

Replication → DNA making identical copies of itself

• Inherent in DNA’s structure is a mechanism for reproducing
itself
• Before a cell can divide, all the DNA must be replicated
(copied)
• Each strand of DNA can be viewed as a template
o Can produce a "reverse image" copy of itself
o Each new strand of DNA produced has a sequence
of bases exactly complementary to the template
strand.

Steps of DNA Replication

1. Unzipping: the DNA double helix unwinds, and the two strands of DNA separate; hydrogen bonds between
the bases break
• Performed by enzyme Helicase

2. Complementary Base Pairing: new nucleotides move in to pair up with bases of each template strand of
DNA.
• New nucleotides are always floating around within the nucleoplasm.
• Performed by enzyme DNA Polymerase

3. Nucleotide Bonding: covalent sugar-phosphate bonds form between adjacent nucleotides of the new
strand to complete the molecule.
• Performed by enzyme Ligase
• New molecules wind into a double helix.

Semi-Conservative Replication
• Each new strand of DNA produced contains one "old" strand (the template) and one new strand.
• Product of replication by one DNA molecule is two complete double-stranded DNA molecules, each with one
new strand and one original stand that acted as a template for replication.

G A C A A C T G G A T C G A C DNA

C T G T T G A C C T A G C T G DNA

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 RNA (Ribonucleic Acid)

RNA is necessary in all organisms for protein synthesis to occur

H O

RNA molecules also consist of nucleotides H N H

2
o Each RNA nucleotide is also composed of three subunits: O 5'
N

1. pentose sugar ribose O- P O CH2 O

O

O-
2. phosphate group that is attached to H
H H
H
one end of the sugar molecule
3' OH OH
3. one of several different nitrogenous
bases linked to the opposite end of the Uracil
ribose.

• Uracil is used instead of Thymine (G, A, C, are otherwise the

same
• RNA is single-stranded, so is not a double helix.

Transcription

DNA ➔ mRNA

Challenge: DNA does not leave the nucleus but proteins are made in the cytoplasm
Solution: Transcription is the “photocopying” stage by the synthesis of mRNA

STEPS OF TRANSCRIPTION:
1. A specific section of DNA unwinds, exposing a set of bases
2. Along one strand of DNA (called the "sense" strand), complementary RNA bases are brought in.
a. Performed by the enzyme RNA polymerase

b. In RNA, Uracil binds to the Adenine on DNA. As in DNA, cytosine binds to guanine.

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 c. The other strand of the DNA molecule (the “missense” strand), isn’t read.

3. RNA strand is released from DNA

4. DNA molecule rewinds, and returns to its normal
double helix form.
5. mRNA strand is processed (certain sections called
introns are cut out, a "Poly-A" tail is added to the 3'
end, and a "cap" is added to the 5' end)
6. mRNA leaves the nucleus via the nuclear pores and
moves into the cytoplasm.

G A C A A C T G G A T C G A C DNA

C U G U U G A C C U A G C U G mRNA

Types of RNA: rRNA, tRNA, and mRNA

RNA that is involved in protein synthesis belongs to one of three distinct types: ribosomal RNA (rRNA), transfer RNA
(tRNA), and messenger RNA (mRNA).

Ribosomal RNA (rRNA)

• Become structural parts of ribosomes and serve as genetic link between mRNA and tRNA
o Ribosomes are the sites of protein synthesis

amino acid Transfer RNA (tRNA)

ribosome
• Deliver amino acids from the cytoplasm to the
ribosome
• Is a different tRNA for each amino acid
• Consist of about 80 nucleotides and are structured in a cloverleaf pattern.

Anticodon
UAC

Messenger RNA (mRNA)

• Carries the genetic code contained in the cell's DNA from the nucleus to the ribosome

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 • Acts as a "go-between" for DNA in the nucleus and the ribosomes in the cytoplasm

“One Gene, One Protein”: The Central Dogma of Molecular Biology

DNA ➔➔➔➔ mRNA ➔➔➔ protein

transcription translation

Translation

Translation occurs after mRNA leaves the nucleus through pores in the nuclear envelope, and enters the cytoplasm

• “Transaltes” the RNA message into the actual

protein
• Occurs on the ribosome.
• Order of the bases in DNA, and thus mRNA,
determines the amino acid sequence of the protein
being made.

Each amino acids is coded for by 3 bases (known as a triplet

code)
• Are 20 different amino acids, but only 4 different
bases in DNA/RNA

Each three-letter unit of mRNA is called a codon.

• There are 43 ( = 64) codons possible --> easily enough codons to code for all the necessary amino acids.
o In fact, the same amino acid is often specified by more than one codon
o However (very important), the reverse is never true
o Any one codon only specifies one amino acid -- there is no vagueness in the code (e.g. CCU will always
produce proline).

Start and Stop Codons

• “Punctuation” of the code
• Tells when to start reading the gene for a particular protein and when to stop
• Start codon corresponds to a specific amino acid, Stop codon is just a "stop" synthesis signal.

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The Genetic Code: the most important chart in Biology
AAU ASPARAGIN CAU HISTIDINE GAU ASPARTIC ACID UAU TYROSINE
AAC E CAC GAC UAC
AAA LYSINE CAA GLUTAMIN GAA GLUTAMIC ACID UAA STOP
AAG CAG E GAG UAG
ACU THREONINE CCU PROLINE GCU ALANINE UCU SERINE
ACC CCC GCC UCC
ACA CCA GCA UCA
ACG CCG GCG UCG
AGU SERINE CGU ARGININE GGU GLYCINE UGU CYSTEINE
AGC CGC GGC UGC
AGA ARGININE CGA GGA UGA STOP
AGG CGG GGG UGG TRYPTOPHAN
AUU ISOLEUCINE CUU LEUCINE GUU VALINE UUU PHENYLALANI
AUC CUC GUC UUC NE
AUA CUA GUA UUA
AUG METHIONIN CUG GUG UUG LEUCINE
E

The genetic code is universal: the same codons stand for the same amino acids in almost all living things
• Suggests that all living things have a common evolutionary ancestor.

Main Steps In Translation:

• can be divided into 3 subprocesses: initiation, elongation and
termination

1. Initiation

a. mRNA, with its start codon (AUG) attaches to the "R"

site of the ribosome.
The AUG codon always initiates translation and codes for
the amino acid methionine.

b. tRNA binds to the start codon of mRNA

tRNA has a binding site of 3 bases called an anticodon that is complementary to the mRNA codon.
The codon of mRNA of AUG is "read" by a tRNA that has a UAC anticodon.
The tRNA that has this anticodon carries, at it's tail, the amino acid methionine.

c. This methionyl-tRNA is in the P site of the ribosome. The A site next to it is available to the tRNA bearing the next
amino acid.

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 2. Elongation
a. More amino acids are added and connected together to form a polypeptide, as specified by the mRNA
sequence
b. An incoming amino-acyl-tRNA (lets call this AA2-tRNA2) has an anticodon that recognizes the codon in the
A site and forms a hydrogen bond
c. A peptide bond is formed between the new amino acid and the growing polypeptide chain.
d. The bond breaks between AA1 and tRNA1
e. The tRNA1 that was in the P site is released, and the tRNA2 in the A site is translocated to the P site.
i. Ribosome moves over one codon along the mRNA (to the right in our diagram; in the 5' ---
-> 3' direction.)
ii. This movement shifts the tRNA2 (which is attached to the growing amino acid chain) to the
P site.
f. tRNA3 with AA3 can now move into A site and bind with the next codon on mRNA.
g. This process repeats, and the chain elongates as long as there are new codons to read on the mRNA.

3. Termination
a. The process above repeats until a special codon, called a stop codon, is reached. There are 3 Stop
codons: UAA, UAG, UGA.
b. The stop codons do not code for amino acids but instead act as signals to stop translation when their
anticodons enters the A-site
c. Protein called release factor binds directly to the stop codon in the A site. The release factor causes a
water molecule to be added to the end of the polypeptide chain, and the chain then separates from the
last tRNA.
d. Protein is now complete
The mRNA is now broken down
Ribosomal subunits separate
e. New protein is sent for final processing into the endoplasmic reticulum and golgi apparatus

Please Label these Parts

Often, many clusters of ribosomes (polysomes) will simultaneously transcribe the same mRNA
• Allows many copies of the same protein can be made quickly

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DNA TTA CGG CTA TGC ATA TTT AGC ACA TGC TCG ATT
mRNA AAU GCC GUA ACG UAU AAA UCG UGU ACG AGC UAA

Protein Asparagine – alanine – valine – threonine – tyrosine – lysine - serine – cystine – threonine – serine - STOP

GENETIC MUTATIONS

Mutation → a change in an organism resulting from the chemical change in the structure of a gene
• Can be caused by both internal and external factors
• Occurs during DNA replication if nucleotides are lost, rearranged, or paired in error
o Resulting change in instruction of the genetic code could lead to a protein that does not function
properly when the DNA's code is translated
• Change will first be reflected in the RNA copy, then in the enzyme or other protein that the RNA codes for, and
finally in the appearance of new traits in the living organism.
• Occurs because of the alteration in one or more base pairs of the DNA molecule, garbling the existing genetic
code

NOTE: Errors in translation are NOT mutations (not a permanent change in DNA that will be carried through
future cell lineages)

Types of Base Changes

1. Substitution → one base pair is substituted for another (also called point mutations)
2. Addition → an extra base is added
3. Deletion → a base is deleted
→ Mutations where bases are added or deleted are called frameshift mutations.

It only takes a single different pair of bases to produce a different organism.

Consider an analogy of a “mutation” to a sentence in English:

Example of the effect of a mutation:

Original message: the big dog bit Ted and ran off
Substitution (point): the bif dog bit Ted and ran off
Deletion (frame shift): the bid ogb itT eda ndr ano ff

Try it for yourself: Here is a section of DNA before a mutation.

DNA T A C G G G C T C T A G C G A G A T A T T
mR A U G C C C G A G A U C G C U C U A U A A
NA
a.a. Methionine Proline Glut. Acid Isoleucine Alanine Leucine Stop

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 Here the same section is after two bases have been switched from the original sequence.
DNA T A C C G G C T C T A G C G G G A T A T T
mR A U G G C C G A G A U C G C C C U A U A A
NA
a.a. Methionine Alanine Glut. Acid Isoleucine Alanine Leucine Stop

Here the same section is after one extra base (a G in the third codon) has been added to the original sequence.
DNA T A C G G G G C T C T A G C G A G A T A T
mR A U G C C C C G A G A U C G C U C U A U A
NA
a.a. Methionine Proline Arganine Valine Arganine Serine Isoleucine

Mutation Effects
• Neutral: base pair change results in the same AA, so there is no effect
• Beneficial: change provides an accidental benefit to the organism
• Harmful: change in AA sequence drastic enough to affect the functioning of the organism (can be lethal)
o Gene mutations can cause genetic disorders

Levels of Mutations:
1. Gene Mutations
• Affect only a single gene.
• May be caused by a change (e.g. substitution, deletions, additions) in a single gene. The effect on the
individual depends on the gene's role.
2. Chromosomal Mutations:
• Occur after chromosomes are damaged (e.g. due to exposure to radiation, addictive drugs, pesticides)
• Pieces of chromosomes can be lost, added, or whole chromosomes can be lost or added.

Genetic Disorders → changes in DNA can directly affect protein synthesis, this in turn can drastically affect metabolism
and body structure

Mutagens → any agent that causes mutations in humans (e.g. benzene, UV light, asbestos, DDT, X-rays)

Gene Mutation Examples

• Sickle cell anemia occurs when one amino acid present
in the hemoglobin is switched due to a point mutation
of a single base pair in one gene
o Prevents hemoglobin from efficiently carrying
oxygen and causes RBCs to clump together and
clog vessels
• PKU (phenylketonuria) occurs when the enzyme that
converts excess phenylalanine into tyrosine is defective
due to a change in the gene that codes for it.
o Results in a build-up of phenylalanine in the
blood, resulting damaging effects and a musty
odor in the breath, skin or urine, caused by too much phenylalanine in the body

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 • Albinism caused by a defective enzyme that converts tyrosine
to melanin is defective
o Results in no skin or hair pigment.

Most birth defects result from a chromosomal abnormality.

The abnormality most frequently appears during meiosis when the egg
and sperm cells are formed.

Chromosomal Mutation Examples

• Down's Syndrome (trisomy 21) – most common chromosomal
abnormality
o Children are born with an extra 21st chromosome
o During the formation of the egg, both number 21
chromosomes end up in the same egg cell.
o When the egg is fertilized by the sperm cell with its single
number 21 chromosome, it produces a child with three number
21 chromosomes per cell.

• Turner's syndrome → absence of a second X or of the Y sex

chromosome
o Result is a female child who is short and infertile.

• Klienfelter’s syndrome → presence of three sex chromosomes,

two X chromosomes and one Y.
o They generally grow tall with long limbs and generally have IQ’s that are significantly below those
of their siblings.
o Spermatogenisis reduced or absent

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