Ch2 Nucleic Acids Convey Genetic Information

Supplemental Text: Essential Genetics: a Genomic Perspective

4th ed Hartl and Jones 2005

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 DNA: The molecule of heredity
• 1869 Friedrich Miesher discovers a weak acid abundant in
cell nuclei: deoxyribonucleic acid, DNA
• 1870’s Chromosomes: thread-like objects in cell nuclei that
split and are passed on during cell division

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 DNA: The molecule of heredity
• 1869 Friedrich Miesher discovers a weak acid abundant in
cell nuclei: deoxyribonucleic acid, DNA
• 1870’s Chromosomes: thread-like objects in cell nuclei that
split and are passed on during cell division
• The number of chromosomes is constant within a species,
but may differ between species
•Chromosomes are made up of DNA (simple structure) and
proteins (diverse structure)

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 DNA: The molecule of heredity
• 1869 Friedrich Miesher discovers a weak acid abundant in
cell nuclei: deoxyribonucleic acid, DNA
• 1870’s Chromosomes: thread-like objects in cell nuclei that
split and are passed on during cell division
• The number of chromosomes is constant within a species,
but may differ between species
•Chromosomes are made up of DNA (simple structure) and
proteins (diverse structure)
•The amount of DNA is constant between cells of an organism
while the amount and type of proteins differ
•The complexity of protein made it the initial favorite candidate
for genetic material
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 Determining the genetic material:
The Griffith Experiment 1928

Rough Smooth
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 Determining the genetic material:
The Avery, MacLeod and McCarty Experiment 1944
DNA extract from S cells

RNase or Protease DNase

Transformation No
Transformation

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 The Griffith Experiment 1928

The Avery, MacLeod and

McCarty Experiment 1944

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 Determining the genetic material:
The Hershey-Chase Experiment 1952

32P DNA 35S Protein

T2 Phage

DNA is the
genetic
material of all
cellular
organisms

Labeled No Labeled
Progeny Progeny
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 DNA Structure

DNA Structure: ~1950

•1st good X-ray photographs
•3’ to 5’ phosphodiester bonds
link nucleotides of DNA
•α helix structure determined
in proteins
•DNA contains purines and
pyrimidine bases
•Chargaff’s rules
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Chargaff’s Rules

Chargaff’s rules:
•Four nucleotides are present in different amounts in different
species
•A=T, G=C
•Purines / Pyrimidines = 1
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 Structure and Gene Replication

•Data suggest an α helical

structure for DNA

•The double-stranded helix

suggested a model of DNA
replication in which each
strand could serve as
template for a new,
daughter, strand

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 Model of DNA replication
•Each parental strand serves as a
template for the production of a
complementary daughter strand

•Order of DNA bases is specified by base

pairing rules: adenine pairs with thymine
and guanine pairs with cytosine

5’- ATGCCGTAG - 3’
3’- TACGGCATC - 5’

5’- ATGCCGTAG - 3’ 5’- ATGCCGTAG - 3’

3’- TACGGCATC - 5’ 3’- TACGGCATC - 5’

•Complementary pairing

•Strands have Antiparallel Directionality

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 Rosalind Franklin and DNA Structure
•In 1962, four
years after the The x-ray micrograph
death of Rosalind from Rosalind
Franklin, Watson, Franklin used by
Crick and Watson and Crick to
Maurice Wilkins determine the
received a Nobel structure of DNA in
Prize for the 1953
double-helix
model of DNA
Crick: “We have discovered
the secret of life.”

“Oh yeah, we did it by

stealing some technician's
data.”

Or did they?
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 DNA: Chemical Composition

• Gene = unique sequence of DNA bases

• Two types of nitrogen-containing bases comprise the
chemical structure of DNA:
- purines = adenine and guanine
- pyrimidines = thymine and cytosine

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 DNA: Chemical Composition

• Nucleoside = sugar +base

• Nucleotides = building blocks of DNA = phosphate + sugar +
base
• Sugar = 5 carbon deoxyribose (ribose in RNA)
• Purine and pyrimidine bases are linked to the 1’ carbon of sugar
• Phosphate to 5’ carbon of sugar
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 DNA: Chemical Structure
• DNA nucleotides = a
chain of bases
• Phosphodiester bonds 5’ end
link sugar molecules
to phosphate groups
• Orientation of sugar-
phosphate linkages =
3’ to 5’ as the
phosphate attached to
the 3’ carbon of one
sugar is linked to the
5’ carbon of the next Phosphodiester
sugar bonds

• Purine and pyrimidine

bases are linked to the 5’ end
1’ carbon of sugar
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 DNA: Chemical Structure

• DNA consists of two

polynucleotide chains which
run 5’ to 3’ in opposite
directions = antiparallel
• DNA chains are held
together by hydrogen bonds
between bases

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 DNA Synthesis

A single protein, DNA pol I, synthesizes the new strand of DNA

Synthesis requires the presence of a DNA template

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 DNA: Chemical Structure

• DNA base pairing is

determined by specificity of
hydrogen bonding between
the bases
- Adenine (A) pairs with
Thymine (T)
- Guanine (G) pairs with
Cytosine (C)

• G-C pairing is stronger than

A-T pairing

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Figure 4-72 Molecular Biology of the Cell (© Garland Science 2008)
Figure 4-15 Molecular Biology of the Cell (© Garland Science 2008)
 3 Models of DNA replication

Disruptive Semiconservative Conservative

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 DNA replication is semiconservative

•1958 Meselson and Stahl

Experiment

•Follow the 15N (heavy) DNA

through multiple
generations of bacteria

•Use centrifugation in a Heavy Intermediate Light and Int.

density gradient to follow
changes in genome density

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 equilibrium density-gradient centrifugation and semi-
conservative DNA replication

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 The linear - primary - sequence

The information stored in DNA must be in the

linear sequence of the four bases
Genes must differ in sequence
Number of different sequences = 4N where N is the
length of the sequence
Average gene is 1000 bases = 41000 different
possibilities >10X the number of genes in a
genome

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 DNA and Protein Synthesis

Protein synthesis occurs at sites where DNA is

absent
Chromosomal DNA is in nucleus, Proteins
synthesis occurs in the cytoplasm
DNA must have an indirect role in proteins
synthesis
RNA acts as an intermediate in the transfer of
information of DNA to Protein

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 RNA
•RNA is present primarily in the
cytoplasm
•RNA is chemically similar to DNA:
Sugar is ribose, not
deoxyribose
RNA contains no thymine,
Uracil instead

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 RNA and DNA

•RNA can form complementary helices with DNA

•RNA is generally found as single-stranded molecules
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 Central Dogma of molecular genetics
• DNA codes for itself =
replication DNA
• DNA codes for RNA = Transcription
transcription
• RNA codes for protein = RNA
translation
Translation
• DNA is the informational
molecule which specifies
the structure of proteins
using RNA intermediate Protein
• RNA transmits the genetic Movement of information
information in DNA as a from DNA to Proteins is
genetic code in translation
Unidirectional

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 RNA Synthesis

RNA is transcribed from one strand of DNA by RNA polymerase

RNA synthesis always progresses 5’ to 3’
RNA is synthesized in the nucleus and transported to the
cytoplasm
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 RNA Synthesis

Nucleus

Labeled RNA
Same cell 88 minutes later

RNA is synthesized in the nucleus and transported to the

cytoplasm
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 How does RNA determine protein sequence/structure?
Protein synthesis occurs
at Ribosomes = small
RNA containing
structures on
endoplasmic reticulum
Prior to protein synthesis
amino acids are attached
to tRNA molecules
tRNAs serve as adapters
between RNA and amino
acids

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 tRNA Function

mRNA carries the

information for protein
sequence (<4% of RNA)
tRNA molecules, with
attached a.a., bind to
triplets of mRNA, codons,
through anticodon

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 Translation

• Messenger RNA (mRNA) contains genetic code in triplet base

codons that specify the sequence of amino acids in proteins
• Transfer RNAs (tRNA) contain triplet base sequences =
anticodon which are complementary to codon sequences in
mRNA and position amino acids during translation
 Ribosome and Protein Synthesis

Protein synthesis occurs at ribosome

rRNA makes up 85% of total RNA
Multiple ribosomes can translate a single mRNA = polyribosome
 The Genetic Code
How to go from 4
bases to 20 a.a.?
Doublets allow
4X4=16
combinations
Triplets 4X4X4=64
Code is Degenerate =
there is more than
one codon for most
a.a.
3 codons code for
termination = stop or
nonsense codons
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 Translation
Direction of Synthesis:
• DNA and RNA are always
synthesized 5’ to 3’
• Template strand of DNA =
3’-to-5’
• mRNA = 5’-to-3’
• polypeptide = amino
terminus (NH2) to carboxy
terminus (COOH)

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