Chapter 3
The Origin of Molecules
and the Nature of Life
Figure CO: Hot thermal spring
Overview of Molecular Evolution
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Natural preconditions
Laboratory reproduction
Only on Earth? Elsewhere?
Specific locations?
RNA, DNA, proteins
“organic” molecules
Life = organisms?
Prerequisites for the Origin of Molecules
• Our Sun and the Earth’s orbit (Goldilocks zone)
– Sun provides steady radiant energy
– Earth’s nearly circular orbit provides a relatively
constant input of light energy
(Goldilocks zones)
Figure 01: Various Molecules Observed
in Molecular Clouds within Our Galaxy
There is also much water, H2O, in the universe.
Adapted from Buhl, D., Origins of Life 5 (1974): 29-40.
Prerequisites for the Origin of Molecules
• Chemicals
– Earth is chemically diverse, in part because it is
part of young solar system
– Carbon – an element well suited to be the
structural basis of life
• Water
– Hydrogen and Oxygen
– Universal solvent
• Nitrogen, Sulfur, Phosphate, Iron, etc.
Elements Found on Earth
92 occur naturally in nature
24 occur naturally in the body
the most common: H, C, O, N
vital elements for life
The Origin of Life
• This is the cover of the first English
edition (1938) of the pioneering
work of the biochemist Aleksandr
Ivanovich Oparin (1894-1981),
published in Russian in 1924 (in
English in 1936)
• Oparin elaborated, within the
framework of Darwinism, the first
successful scientific approach to the
problem of the origin of life,
modernizing the old spontaneous
generation controversy as a new
hypothesis of Biogenesis
(Abiogenesis)
Oparin’s The Origin of Life
• Oparin’s book stands out as a milestone in science
because no one had given serious thought to the
problem of the origin of life after Louis Pasteur
concluded in 1864 that life always came from preexisting life
• To account for life on the Earth, several leading
scientists even proposed that the first forms of life
were delivered to the Earth from elsewhere
(panspermia), but Oparin’s basic premise was that
living systems must have arisen from non-living
chemicals on the early Earth
John Burdon Sanderson [J.B.S.]
Haldane (1892-1964)
• British contemporary of Oparin who
independently proposed (1928) a similar
hypothesis that conditions on the
primitive Earth favored chemical reactions
that synthesized organic compounds from
inorganic precursors: biopoiesis
• Haldane had also suggested that the
earth's pre-biotic oceans – very different
from their modern counterparts – would
have formed a "hot dilute soup" in which
organic compounds, the building blocks of
life, could have formed – the “primordial
organic soup” of early oceans, tidal pools
or warm ponds
J.B.S. Haldane
"Theories have four stages of acceptance.
i) this is worthless nonsense;
ii) this is an interesting, but perverse, point of
view,
iii) this is true, but quite unimportant;
iv) I always said so.“
“J.B.S. Haldane was perhaps the most brilliant science
populariser of his generation.” Arthur C. Clarke
Harold Urey & Stanley Miller
In 1953, Harold C. Urey
and his graduate
student, Stanley L.
Miller, at the University
of Chicago conducted
experiments that
simulated hypothetical
conditions present on
the early Earth and test
for the occurrence of
chemical evolution
“Life” Sparked in Test Tubes:
The Miller-Urey Experiments
• Heated water, simulating
vulcanism, produced water
vapor circulating through the
closed system of glass
chambers
• Miller and Urey placed gases
into the upper chamber
thought to be present in
Earth’s early reducing
atmosphere, and applied a
repeating spark to simulate
lightning
“Life” Sparked in Test Tubes:
The Miller-Urey Experiments
• Condensers cooled the gases
and vapors, causing
molecular reaction products
to collect in the water
• Samples were taken from this
water over the next week and
analyzed
• Many simple and some
surprisingly complex organic
molecules were recovered
Miller-Urey Products
• Among the organic
molecules formed were
amino acids, basic building
blocks of protein
• Subsequent follow-up
trials, by many other
biologists, using various
combinations of “primitive
atmospheres,” produced
even more complex
organic compounds
• Sugars, lipids, and some of
the building blocks for
nucleic acids were also
formed
Sidney Walter Fox (1912 - 1998)
• In 1958 Fox and Kaoru Harada
reported that heating dry amino
acid mixtures to 180oC produced
polymers resembling proteins
• The dry heat actually melted the
amino acids and baked out water
molecules so that chemical bonds
formed that linked the amino acids
together into polymers they called
thermal condensation products, or
proteinoids
Sidney Walter Fox (1912 - 1998)
• In the 1960s, Fox and his collaborators found that
under certain conditions proteinoids assembled into
microscopic spherical balls, which they referred to as
proteinoid microspheres
• These were similar to the coacervate described by
Oparin, and the fact that they were composed of
amino acid polymers made them a more attractive
model of a prebiotic protocell than the mixture of
gelatin and gum arabic that Oparin had studied
• Furthermore, dry heat seemed to be a very plausible
energy source for driving condensation reactions
Chemical Development of Prebiotic
Organic Compounds - How?
coacervate droplets
• Other simulation experiments can generate building
blocks from the primordial soup
– Miller and Urey formed amino acids
• Gaseous H2, CH4 (methane), NH3(ammonia), H2O(steam)
• Sparks (simulate atmospheric lightning)
– Oparin and Fox formed protobionts, proteinoids, &
microspheres (also called coacervate droplets)
• These molecular collections mimic cell behavior, but are non-living
Replicating the Production of the First
Molecules in the Laboratory
• Miller-Urey type experiments continue to be
carried out to this day, using a variety of
ingredients and experimental conditions
• Evolution of carbon-based molecules was not
as unlikely an event as had previously been
thought
Possible Sites for the Origin of the First
Molecules on Earth
• Hydrothermal vents
– Thermophilic (heat-loving)
organisms
• Volcanoes
– Sponge-like minerals (zeolites)
that can retain and catalyze
organic compounds
• Clays
– Layered clays served as
polymerizing templates
Chemical Development of Prebiotic
Organic Compounds -How?
• Bada and Miller's “sub-ice organic gazpacho” theory (ice as
a catalyst for abiosynthesis reactions)
• Amino acids of extraterrestrial origin
– Carbonaceous chondrite meteorites contain organic compounds,
amino acids, fatty acids, etc.
– Murchison Meteorite, Australia (L) and Allende Meteorite (~2
tons), Mexico (R)
What Came Next From the
Primordial Organic Soup?
• Phospholipids (of an appropriate length) can spontaneously form
lipid bilayers, a basic component of the cell membrane.
• The polymerization of nucleotides into random autocatalytic RNA
molecules might have resulted in self-replicating ribozymes (RNA
world hypothesis).
• Natural Selection pressures for catalytic efficiency and diversity
result in ribozymes which catalyse peptidyl transfer (hence
formation of small proteins), since oligopeptides complex with RNA
to form better catalysts. Thus the first ribosome is born, and
protein synthesis becomes more prevalent.
• Proteins outcompete ribozymes in catalytic ability, and therefore
become the dominant biopolymer. Nucleic acids are restricted to
predominantly genomic use.
Increased Complexity of Organic
Molecules - How?
• Amino acids are monomers
– Monomers must peptide bond to form proteins
– This requires an input of energy and removal of
water
• How could this occur?
– Evaporation?
• Tidal pools?
– Freezing?
– Chemical dehydration?
– Bonding to charged mineral surfaces?
• Clays? Pyrites?
Biopoesis Again
• Biologist John Desmond Bernal (1901-1971)
coined the term Biopoesis for this process, and
suggested that there were a number of clearly
defined "stages" that could be recognized in
explaining the origin of life in the 1960s.
• Stage 1: The origin of biological monomers
• Stage 2: The origin of biological polymers
• Stage 3: The evolution from molecules to cell
– Bernal suggested that evolution (natural selection)
may have commenced early, some time between
Stage 1 and 2.
Biopoesis in Three Stages
Biopoesis
• Abiogenesis/Biopoesis remains an exciting area for
current research
DNA, RNA and Proteins
• Three fundamental
classes of
molecules are
associated with
modern life
• Replication,
transcription,
translation
Figure 03: DNA replicates and
information is transferred from DNA
to RNA to protein
Figure 02: Mutual Dependence of Information
Carried by Nucleotide Sequences
The mystery: which
came first, DNA, RNA,
or protein?
Which of These Molecules Evolved
First: DNA, RNA or Protein?
• DNA First? (“DNA World”)
– Protein synthesis depends on
the prior existence of RNA and
DNA.
• Proteins First? (“Protein
World”)
– Some amino acid polypeptides
form without DNA.
• RNA First? (“RNA World”)
– RNA could catalyze chemical
reactions and replicate
History of Chemistry for
the Origin of Life
The RNA World refers to a hypothetical stage in
the origin of life on Earth
It Was a Small RNA World After All
• The phrase "The RNA World" was
coined by Walter Gilbert in 1986 in a
commentary on the then recent
observations of the catalytic
properties of various RNAs
• However, the idea of independent
RNA life is older and can be found in
Carl Woese's book The Genetic
Code (1967)
• Five years earlier, the molecular
biologist Alexander Rich, of the
Massachusetts Institute of
Technology, had posited much the
same idea in an article
The RNA World
• During the time of the RNA
World, proteins were not yet
engaged in biochemical
reactions
• RNA carried out both the
information storage task of
genetic information and the
full range of catalytic roles
necessary in a very primitive
self-replicating system
• Later RNA catalyzed the
formation of DNA
DNA
RNA
Other?
Other?
Abiogenesis
RNA?
Quick Review
• Were there other early
lifeforms with other
molecular mechanisms
of inheritance beyond
the “RNA world?”
• Who knows?
• Perhaps finding life
elsewhere in the
universe will
demonstrate them?
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Nucleic Acids
DNA Replication
RNAs
Transcription
Translation
• DNA is the genetic material
Nucleic Acids
– made of 4 building blocks –
nucleotides
• adenine (A), guanine (G),
cytosine (C), thymine (T)
• A-T, C-G in the chain
• double helix model
• double stranded DNA
• RNA carries hereditary
information from nuclear
DNA to the cytoplasm
(inside cells)
– uracil (U) replaces T
– single stranded RNA
Complimentary
Base-Pairing
The Structure of the Genetic Material
DNA Forms a Template for Its
Semiconservative Replication
DNA Replication
• semi-conservative
• helicase – unwinds
DNA
• DNA polymerases
– one strand is the
template
– builds a
complementary
strand
– bases pair with
hydrogen bonds
• A-T
• C-G
DNA Replication Enzymes
DNA Primase, DNA Replicase, DNA Polymerase III, DNA Polymerase I
(DNA Polymerse II is a repair enzyme)
DNA Replication in a Bacterium
• The circular bacterial DNA begins replication at a
single site, the replication origin
• Replication proceeds out in both directions, until
copies of each strand of DNA are produced
Information Transfer—
DNA to RNA to Protein
• DNA triplets transcribed to
produce complementary codon
triplets in mRNA
• Each mRNA codon triplet
specifies a particular amino acid
• Sequentially, codon by codon,
the mRNA is a blueprint used in
translation to produce a
particular protein molecule
Three RNAs in Protein Synthesis
• Different types of RNA
play a different role in
the synthesis of protein.
– mRNA
– rRNA
– tRNA
• Transcription (in nucleus*)
– DNA – gene blue print
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–
–
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Two Stage
Protein Synthesis
triplet code - 3 bases/AA
template
exons - expressed
introns – excised
– RNA – tools for protein
synthesis
• mRNA
• tRNA
• rRNA
• Translation (in cytoplasm)
– Ribosome
• codons are read to build a
primary protein structure
* No nucleus in the prokaryotes
Transcription I
Transcription II
Exons = coding
sequences
Introns = non-coding
seqeunces
Translation Uses the Codon Dictionary
alternate CUG start codon in some vertebrate immune cells
The common code is possibly the
strongest evidence of all for the
common ancestry of all life on Earth
Translation at the Ribosome
In Organisms, Information Flows from
DNA to RNA to Proteins
The Central Dogma
Of Molecular Biology
The Genetic Code
Is
Universal
and
Redundant
and
Unambiguous
The Genetic Code
• The code is universal because it specifies the
same 20 amino acids in all organisms with
only few exceptions
• The code is redundant because there are
multiple codons which code for the same AA
• The code is unambiguous because any one
codon codes for only one amino acid
• The code is a triplet code because 3 bases
represent a single AA in a codon
The Lac Operon
• The Lac Operon is a classic
example of negative
feedback gene regulation in
prokaryotes
The Lac Operon
• When lactose is absent then
there is very little Lac enzyme
production (the operator has
LacI repressor bound to it)
• When lactose is present but
a preferred carbon source
(like glucose) is also present
then a small amount of
enzyme is produced (LacI is
not bound to the operator)
The Lac Operon
• When lactose is the
favored carbon source
(e.g., in the absence of
glucose) cAMP-CAP binds
upstream of the promoter
at a specific site
• This allows the RNA
polymerase to bind to the
promoter and Lac enzyme
production is maximized
Why The Lac Operon?
• Consider mice : life
span perhaps 2 years
• Mouse pups weaned at
3 weeks
• In optimal growth
conditions E. coli will
divide every 30 minutes
• 3 weeks is at best, 1008
E. coli generations
• 2 years is at best, 35040
E. coli generations
Molecules and Life
• What is Life?
– Associated with DNA, RNA and proteins
– DNA as the central molecule of life – hereditable
information; Carbon -- structural, physiological
and metabolic
– Organic molecules can be formed abiotically
– Did life begin with molecules around 4.5 Bya, with
cells 3.5 to 3.8 Bya, or with the first protoorganisms at some point in between?
What are the Properties of Life?
1) Organization: Composed of one or more cells, the basic unit of life.
2) Metabolism: Transform energy by converting chemicals and energy into
cellular components (anabolism) and decomposing organic matter
(catabolism) to generate useful energy.
3) Homeostasis: Regulation of the internal environment to maintain a
relatively constant state.
4) Growth: Maintain a higher rate of anabolism than catabolism to
increase size and complexity and repair damage to the cell or organism.
5) Adaptation: The ability to change over time in response to the
environment. Individuals develop and populations evolve.
6) Response to stimuli: A change in activity (metabolism, behavior, etc.)
appropriate to the change in the environment which was the stimulus.
7) Reproduction: The ability to produce new individual organisms, either
asexually, or sexually.
Living Systems
• The Central Dogma:
DNA  RNA  Protein
explains how life on
earth today, and since
the RNA World was
replaced by the DNA
World, manages to
achieve those seven
fundamental properties
Figure 03: DNA replicates and information is transferred from DNA to RNA to protein
Enzyme Action and Regulation
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Enzymes are protein
catalysts
Enzymes are key
products of the
genetic blueprints for
living systems
Again, it is thanks to
enzymes that living
systems achieve the
seven fundamental
properties of life
Chapter 3
End