Chapter 8

DNA: the molecule of heredity

Overview

 What Is the Structure of DNA?

 How Does DNA Encode Genetic
Information?
 How Does DNA Replication Ensure
Genetic Constancy During Cell Division?
 What Are Mutations, and How Do They
Occur?
 How Does Gene Expression and
Regulation Occur?
DNA is composed of four nucleotides
 DNA is made of chains of small subunits called
nucleotides
 Each nucleotide has three components:
1. A phosphate group
2. A deoxyribose sugar
3. One of four nitrogen-containing bases:
− Thymine (T)
− Cytosine (C)
− Adenine (A)
− Guanine (G)
DNA is composed of four nucleotides

phosphate phosphate

base  thymine

sugar base  adenine sugar

phosphate phosphate

base  cytosine

sugar sugar
base  guanine
DNA is composed of four nucleotides
 In the 1940s Erwin Chargaff, a biochemist at
Columbia University, analyzed the amounts of the
four bases in DNA from diverse organisms
 He discovered a consistency in the equal amounts
of adenine and thymine, and equal amounts of
guanine and cytosine for a given species, although
there was a difference in proportion of the bases
 This finding was called “Chargaff’s rule”
A=T
G=C
 DNA is a double helix of two nucleotide
strands
 In the 1940s, several other scientists investigated
the structure of DNA
 Rosalind Franklin and Maurice Wilkins studied the
structure of DNA crystals using X-ray diffraction
 They bombarded crystals of purified DNA with X-
rays and recorded how the X-rays bounced off the
DNA molecules
 The resulting pattern does not provide a direct
picture of the DNA structure, but the researchers
were able to extract specific information
 DNA is a double helix of two nucleotide
strands
Wilkins and Franklin deduced the following
information about DNA from the patterns they found:
1. A molecule of DNA is long and thin, with a uniform
diameter of 2 nanometers
2. DNA is a helical, twisted like a Corkscrew or a
spiral staircase
3. DNA is a double helix
4.DNA has repeating subunits
5. Phosphates are probably on the outside
 DNA is a double helix of two nucleotide
strands

 James Watson and Francis

Crick combined the
X-ray data with bonding
theory to deduce the
structure of DNA
 They proposed that a single
strand of DNA is a polymer
consisting of many
nucleotide subunits
 DNA is a double helix of 2 nucleotide strands
 Within each DNA strand,
the phosphate group of
one nucleotide bonds to
the sugar of the next
nucleotide in the same
strand
 The deoxyribose and
phosphate portions
make up the sugar-
phosphate backbone
 In one DNA strand: an
unbonded sugar at one
end and an unbonded
phosphate at the other
end
DNA is a double helix of 2 nucleotide strands

 The DNA model consists of two

DNA strands, assembled like a
twisted ladder
 The bases protrude inward
toward each other from the
sugar-phosphate backbone like
rungs on a ladder
 Hydrogen bonds hold the base
pairs together, composing the
rung
DNA is a double helix of 2 nucleotide strands

 The two strands in a

DNA are antiparallel;
they are oriented in
opposite directions
 From one end of the
DNA, if one strand
starts with the free
sugar and ends with
the free phosphate, the
other strand starts with
the free phosphate and
ends with the free
sugar
DNA is a double helix of 2 nucleotide strands

 Hydrogen bonds between

complementary bases
hold two DNA strands
together in a double helix
 Adenine and guanine are
large molecules; thymine
and cytosine are relatively
smaller
 Because base pairing
always places a large
molecule with a small one,
the diameter of the double
helix remains constant
 How Does DNA Encode Information?

 How can a molecule with only 4 simple parts be the

carrier of genetic information?
 The key lies in the sequence, not number, of
subunits
 Within a DNA strand, the four types of bases can
be arranged in any linear order, and each unique
sequence of nucleotide represents a unique set of
genetic instruction
 How Does DNA Encode Information?
 The genetic code is analogous to languages, where
small sets of letters combine in various ways to
make up many different words

 For example: English has 26 letters

 The sequence of only four nucleotides can produce

many different combinations

 A 10 nucleotide sequence can code for greater

than 1 million different combinations
 How Does DNA Replication Ensure Genetic
Constancy During Cell Division?

 Replication of DNA Is a Critical Event in a Cell’s

Life
 DNA Replication

 All cells come from pre-existing cells

 Cells reproduce by dividing in half

 Each of two daughter cells gets an exact copy

of parent cell’s genetic information

 Duplication of the parent cell DNA is called

replication
DNA Replication
 DNA replication begins
when DNA helicases
separate the two strands
– Hydrogen bonds between
bases are broken

 A second strand of new

DNA is synthesized by
DNA polymerases, which
position free nucleotides
across from complementary
nucleotides
DNA Replication

 Base pairing is the foundation of DNA replication

– An adenine on one strand pairs with a thymine on
the other strand; a cytosine pairs with guanine
– If one strand reads ATG, the other reads TAC
DNA Replication

The two resulting

DNA molecules
have one old
parental strand and
one new strand
(semiconservative
replication)
What Are Mutations And How Do They Occur?

What are mutations?

– mutations: infrequent changes in the nucleotide
sequence

– often harmful- can cause organism to die quickly

– Some have no functional effect

– Some may be beneficial and provide an advantage

to an organism in certain environments (basis for
evolution)
 Replication And Proofreading
 During replication, DNA polymerase mismatches
nucleotides once every 1,000 to 100,000 base
pairs
 Completed DNA strands contain only about 1
mistake in every 100 mill to 1 bill base pairs
 In humans, this amounts to less than 1 error /
chromosome / replication
 DNA repair enzymes “proofread” each new
daughter strand, replacing mismatched
nucleotides
 However…
Mistakes Do Happen

DNA is damaged in a number of ways

 Certain toxic chemicals (some components of
cigarette smoke)
 Some type of radiations: UV light from the sun
causes DNA damage
 DNA damage leads to uncontrollable cell
division and skin cancer
Types of Mutations

 Point mutation - individual nucleotide in the

DNA sequence is changed
 Insertion mutation - one or more nucleotide
pairs are inserted into the DNA double helix
 Deletion mutation - one or more nucleotide
pairs are removed from the double helix
Types of Mutations

 Inversion - piece of DNA is cut out of a

chromosome, turned around, and re-inserted
into the gap
 Translocation - chunk of DNA (often very
large) is removed from one chromosome and
attached to another
DNA provides instructions for protein synthesis

 DNA can not directly synthesize proteins. It

directs protein synthesis through intermediary
molecules of ribonucleic acid -RNA
DNA provides instructions for protein synthesis
Gene expression: Transcription, translation

 Information in DNA is used to synthesize protein in

two steps:

− Transcription, the transfer of genetic information

from DNA into an RNA molecule

− Translation, the transfer of information from RNA

into a protein
Gene expression
(protein
synthesis) is a
two-step
process
Transcription
Three types of RNA required for protein synthessis
Translation uses complementary base pairing between
mRNA codons and tRNA anti-codons

tRNAs
Ribosome

mRNA
 Next amino acid
to be added to
polypeptide

tRNA binding sites

Growing
polypeptide
P site A site

Ribosome tRNA
Large
mRNA subunit mRNA
binding Small
site subunit
Codons
(a) A simplified diagram
of a ribosome

(b) The “players” of translation

Figure 10.16
The Genetic Code
– The genetic code is:
– The set of rules relating nucleotide sequence to
amino acid sequence
– Shared by all organisms
 Second base of RNA codon

Phenylalanine Tyrosine Cysteine

(Phe) (Tyr) (Cys)
Serine
(Ser) Stop Stop
Leucine
(Leu) Stop Tryptophan (Trp)

Third base of RNA codon

First base of RNA codon

Histidine
(His)
Leucine Proline Arginine
(Leu) (Pro) (Arg)
Glutamine
(Gln)

Asparagine Serine
Isoleucine (Asn) (Ser)
(Ile) Threonine
(Thr)
Lysine Arginine
Met or start (Lys) (Arg)

Aspartic
acid (Asp)
Valine Alanine Glycine
(Val) (Ala) (Gly)
Glutamic
acid (Glu)
 Gene 1

DNA molecule
Gene 2
Gene 3

DNA strand

TRANSCRIPTION

RNA

TRANSLATION Codon

Polypeptide
Amino acid
Figure 10.10
How is gene expression regulated?

 Control can happen at

several points in the
process

 Control to turn on/turn

off protein production

 Control amount of
protein production
 How is gene expression regulated?

 Transcriptional
regulation involves
regulatory “repressor”
and/or “activator”
molecules

 Transcription factors –
molecules required to
promote binding of
RNA polymerase to a
gene promoter
How is gene expression regulated?

 mRNA is “silenced” by RNA

interference (RNAi)

 siRNA molecules (small

interfering RNAs) are double
stranded RNA molecules that
when activated, degrade (cut up)
specific mRNA molecules,
silencing gene expression
 Effects of mutations

 Inversion and translocations: if a gene is split in two,

it will no longer code for a functional protein.

 Deletion and insertion: cause incorrect protein with

non-funcational

 Substitutions: cause changed or unchanged amino

acid, or incomplete protein by premature stop codon
Effects of mutations