DNA Structure

https://www.verywellhealth.com/what-is-dna-5091986

SCIE1106 Lecture 6 – Dr Mitali Sarkar-Tyson

School of Biomedical Sciences, Microbiology and Immunology Discipline
mitali.sarkar-tyson@uwa.edu.au
Reference: Alberts, Molecular Biology of the Cell, Chapter 4
Lecture Outcomes

• List hypotheses on the origin of life on earth.

• Know the main events which led to the discovery of DNA.
• Be able to describe the main features of DNA.
• Understand how the genetic code works.
• Know what is meant by “The Central Dogma”.
• Know the terminology for bases, nucleotides, nucleosides, deoxy,
ribo.
• Be able to define the terms antiparallel, complementary base
pairing, coding strand, codon, right-handed helix, major groove.

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Four hypotheses on origin of life on earth
1. Organic chemical synthesis in a reducing atmosphere
2. Carriage by meteorites
3. Organic chemical synthesis in deep ocean vents
4. RNA world

James W. Brown, NC State University 3

 1. Organic chemical synthesis in reducing
atmosphere
• Was thought that early earth had a
reducing atmosphere, rich in hydrogen
and methane.

• Miller, S.L. (1953) subjected methane,

ammonia & hydrogen gas mixture to
electrical discharges in presence of water
(famous Miller-Urey experiment).

• Prebiotic soup resulted (amino acids and

nucleotides).

• No data on how soup forms organic

networks encompassed by a membrane.

• But was primitive atmosphere reducing?

Current consensus is that it was not.
https://socratic.org/questions/how-did-the-miller-urey-experiment-model-
conditions-of-early-earth
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 2. Carriage by meteorites/comets
• “Panspermia” - attractive theory due to sudden appearance of life on earth
and its amazing uniformity (but no data).
 Organic compounds common in space.
 Amino acid glycine found in comet (2009, NASA).
 Complex organic chemicals could arise on Titan, based on studies
simulating its atmosphere (2013, NASA).
 Mars rocks blasted into space by meteor impacts, carrying microbes?
• Only moves the question backwards – how did life originate elsewhere?

https://www.newscientist.com/definition/panspermia/ https://astrobiology.nasa.gov/news/in-search-of-panspermia/ 5
 3. Synthesis on metal sulphides in deep
sea vents
• Vents are sites of abundant biological activity, much of it independent
of solar energy.
• Energy source, chemical source leads to another prebiotic soup.
• Prebiotic soup self-organizes into life-supporting networks on metal
sulphide surfaces.
• Networks incorporate into membranes (no data).

Hydrothermal vents spew hot chemicals into the surrounding environment. https://asm.org/Articles/2019/May/Probing-the-Depths-of-Life
(Image credit: OAR/National Undersea Research Program (NURP), NOAA) 6
https://www.space.com/19439-origin-life-earth-hydrothermal-vents.html
 4. RNA world
• Was the first self-replicating entity simpler than a cell?
• Short RNA molecules were discovered that can store information and
catalyse chemical reactions (ribozymes)
• RNA molecules have been synthesised that are capable of self-replication
• How did lipid membrane form around RNA?

There are numerous other

hypotheses, see:
https://www.livescience.com/133
63-7-theories-origin-life.html

RNA has been synthesized in conditions that may have resembled those on the early Earth.Credit: Alamy;
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https://www.nature.com/articles/d41586-019-02622-4
DNA Representations

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Discovering the DNA structure
Watson and Crick 1953
The Cavendish Laboratory, Cambridge UK
Now an administrative office

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 Behind the Discovery
• James Watson sees X ray diffraction image of DNA shown by Maurice Wilkins
(Kings College London) at conference in Naples.

• Frances Crick works on helical diffraction in proteins in the same laboratory.

• November 1951 better X ray data from Rosalind Franklin (Kings College).

• Watson and Crick produce a three-stranded DNA model.

• Franklin points out this model’s inconsistencies with her data.

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 Behind the Discovery
• July 1952 Edwin Chargaff visits laboratory and points out his 1947
data on the unity of A/T and G/C ratios from various DNAs

• A flawed manuscript from Linus Pauling (protein structure guru)

prompts Watson to seek latest X ray diffraction data from Wilkins

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 Behind the Discovery
• April 1953 Nature co-publishes the Watson & Crick double helical,
base-paired model of DNA structure together with X ray diffraction
papers from Wilkins and Franklin groups
• Watson, Crick and Wilkins get the Nobel Prize 1962 (Franklin died
1958)

Reading material: The Double

Helix : A Personal Account of
the Discovery of the Structure
of DNA by J. Watson

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 Moving back & Moving on
• DNA is the genetic material

• DNA is a base-paired, anti-parallel, right-

handed double helix

• The code is cracked (triplets of A, T, G

and C code for individual amino acids,
the building blocks of proteins

• Gene to protein relationships established

• Control of gene expression partly

elucidated

• Large scale sequencing of genomes now

common

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 How does the genetic code work?

• Backwards explanation with an example

• Highly active neuropeptide present in human brains: met-enkephalin
• The amino acid sequence is
(N) Met Tyr Gly Gly Phe Met (C)
• The DNA code is
(5’) ATG TAT GGT GGT TTT ATG (3’)

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 How does the genetic code work?
Taken three at a time, 64 combinations are possible, which is enough
to characterise the 22 amino acid plus a ‘stop’.

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 How does the DNA code look in context?

5’ …………… ATG TAT GGT GGT TTT ATG ….……….... 3’

Upstream Downstream
Controls Controls

• Control regions are specific sequences of G, A, T and C, but not

organized in triplets

• Code is composed of four letters with three being used for each
specification. Compared to the 1/0 code of binary computing

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 The Central Dogma/Overview

Transcription Translation

DNA RNA Protein

Reverse
Transcription

Replication

1. Properties 1. Properties 1. Properties

2. Manufacture 2. Manufacture 2. Manufacture
3. Mutation and repair 3. Main types and functions 3. Functions

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Nucleotides: The Building Blocks Of
DNA/RNA

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 Terminology for nucleotides and
nucleosides
Base Abbreviation Sugar + Base Sugar + Base + Phosphate
(nucleoside) (nucleotide)

Adenine A Adenosine Adenosine monophosphate

Guanine G Guanosine Guanosine monophosphate

Cytosine C Cytidine Cytidine monophosphate

Thymine T Thymidine Thymidine monophosphate

Uracil U Uridine Uridine monophosphate

DNA contains Thymine but not Uracil

RNA contains Uracil but not Thymine
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 Terminology Continued
• If sugar is deoxyribose, prefix names with deoxy
– Deoxyadenosine
– Deoxyadenosine monophosphate (dAMP)
– Deoxyadenosine triphosphate (dATP)

• If sugar is ribose, prefix names with ribo

– Riboadenosine triphosphate (rATP)

• DNA (deoxyribonucleic acid) contains deoxyribose

• RNA (ribonucleic acid) contains ribose

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How The Chain Is Linked

The 5’ phosphate can form a

phosphodiester bond by reacting with
the 3’ OH group of another nucleotide

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Hydrogen Bonding Between Bases
A to T and G to C

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 Double-stranded DNA
Important features to remember:
1. Strands are opposite directions (i.e.
ANTIPARALLEL)

2. Strands are COMPLEMENTARY.

Sequence of one strand defines the
sequence of the other strand from
base pairing rules (A=T & G=C)

3. Information encoded by order of bases 5’

to 3’
One CODING strand & other is
NON-CODING

4. THREE bases = ONE codon

(i.e. codes for 1 amino acid)
e.g. ACG encodes for threonine, TTC encodes phenylalanine

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 DNA Helix is Right-handed
Looking down, double helix follows clockwise path
Right-handed convention
(left-handed helix is a mirror image)

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DNA interaction with Proteins

Proteins can interact with bases in “major groove”

Proteins can recognize specific base sequences.

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 What’s happening with DNA now?
• Genes have been/are being patented
 Update: in 2013 the US Supreme Court
has ruled that human genes cannot be
patented
• “Junk DNA” has been patented
 (87% of the human genome)
• Transgenics and gene KO/KI
developed
 Knock-out mutants: loss/inactivation of
gene
 Knock-in mutants: addition of gene
• Genetic screening moves into
medicine
• Viruses and living cells created from
synthetic DNA constructs
• “Bioinformatics” is born
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 Is there still research on DNA?
• “Junk DNA” is not junk

• DNA can change to other forms (Z

and G) in vivo and such changes
alter gene expression
 Z DNA has a left-handed helix

• Chromosomal position and A-DNA B-DNA Z-DNA

movement within the nucleus is (B-DNA is the most common in cells)
preserved across species and
affects gene expression

• Confocal microscopy of living cells

reveals DNA in real-time as a
“demonic dancer”

G (quadruplex) DNA found in cells

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