Lecture 8: DNA and the Origin of Life
http://commons.wikimedia.org
Part 1: DNA and RNA, and their
role in cell function, heredity,
and evolution.
All life on Earth uses DNA to store and
transmit an organism’s cellular “operating
instructions”.
DNA = double-helix polymer formed of a sugar and phosphate
backbone + 4 base-pair molecules.
Genetic code (genes and genome) and the mechanism of
replication.
RNA determines a cell’s function, synthesizing proteins and
enzymes.
Mutations, changes in DNA instructions, are the molecular basis of
evolution.
Towards understanding the role of DNA
1870’s: Scientists concluded that hereditary factors
reside in cell nucleus.
- e.g. Oskar Hertwig’s observations of sperm & egg
fusion in the sea urchins.
1880-1900: Understood that chromosomes - threadlike structures in nuclei - may play a role in heredity
- e.g. Walther Flemming showed chromosomes divide,
separate, split in cell division
1910: Knew that chromosomes are
vectors of heredity - sites of hereditary
factors or “genes”
- e.g. Thomas Hunt Morgan experiments
with fruit flies
• By 1930s most biologists understood that there was a
giant “hereditary molecule” making up chromosomes.
They had even isolated the makeup of this molecule
“DNA”. The challenge was to determine how its
structure accounts for its role in heredity.
• Rosalind Franklin & her student Maurice Wilkins, used a
technique called X-ray crystallography to image the
DNA molecule.
Rosalind Franklin
1952
Later, her student (Wilson) showed
James Watson the DNA image
without Rosalind Franklin’s
approval!
James Watson & Francis Crick
are generally credited with first understanding DNA
Franklin’s x-ray diffraction pattern of DNA
James Watson & Francis Crick
(1953) showed how DNA can
store and replicate information.
Watson & Crick used characteristics and
features of the Franklin & Wilkins image to
develop the chemical model of DNA molecule.
- Nobel Prize in 1962 for Watson, Crick & Wilkins
- Rosalind Franklin had died 4 years earlier,
making her ineligible for the Nobel Prize.
DNA Molecule
DNA is a very long-chain polymer molecule
consisting of base pairs that act as a genetic code.
Sequences of base pairs
code various cell functions:
protein synthesis
RNA synthesis
regulation of synthesis
The unit is a “gene” which
codes for a single function.
Wasserman, Dungan, & Cozzarelli (1985)
Human DNA contains
~3 Billion base pairs
- divided into 23 chromosome pairs
- 2nm wide, ~5 cm long (like a ladder 500 miles high)
DNA: The Double Helix
The “message” of DNA is written in
a sequence of base pairs
Adenine pairs with Thymine.
Thymine pairs with Adenine.
Guanine pairs with Cytosine.
Cytosine pairs with Guanine.
Sugar-phosphate
backbones
Connected by
“DNA bases” that
come in pairs.
C
5ʹ′ end
G
C
Hydrogen bond
G
C
G
3.4 nm
C
G
C
G
1 nm
T
T
C
C
A
G
T
3ʹ′ end
T
A
T
G
C
A
G
G
A
C
G
A
C
A
T
A
T
3ʹ′ end
C
G
T
A
(a) Key features of
DNA structure
0.34 nm
5ʹ′ end
(b) Partial chemical structure
(c) Space-filling
model
DNA provides the instruction manual for
building proteins out of amino acids.
22 different amino acids used by life.
Imagine there is a “word” for each amino
acid; a chain of words gets mapped to a
sequence of amino acids to build proteins
What are the “words”?
DNA provides the instruction manual for
building proteins out of amino acids.
22 different amino acids used by life.
Could be 4 different one-letter words: A,C,T,G.
4 < 22, not enough!
DNA provides the instruction manual for
building proteins out of amino acids.
22 different amino acids used by life.
Could be 4×4 = 16 different two-letter words:
AA,AC,AT,AG,CA,CC,CT,CG,TA,TC,TT,TG,GA,GC,GT,GG.
16< 22, not enough!
DNA provides the instruction manual for
building proteins out of amino acids.
22 different amino acids used by life.
If the words are 3-letters long we get:4×4×4 = 64 combinations.
AAA TAA CAA …
AAT TAT CAT …
AAC TAC CAC …
AAG TAG CAG …
64 > 22, enough!
3 letter words are the most
efficient way to do it. It’s what
nature does.
Each 3-base “word” codes for a different amino acid,
or for the start or end of a protein chain.
The double helix structure
allows replication of DNA.
1. The helix unzips, splitting the base
pairs.
2. Each single strand’s matching bases
are added by an enzyme.
3. The result is a (usually) perfect copy of
the DNA.
The replication of DNA inside a cell nucleus
is the first step of cell division.
Each “daughter” cell inherits a copy of the DNA
instruction manual.
RNA is a single-stranded helix with a different backbone
from DNA, and with Uracil instead of Thymine.
RNA does 3 things:
1. Copies instructions from DNA.
2. Transports amino acids for synthesis
3. Catalyzes protein synthesis.
Nucleic Acids are the basis for the storage and
transmission of hereditary information in all cells.
DNA Deoxyribonucleic Acid
Encodes instructions for
making proteins and RNA.
RNA
Ribonucleic Acid
Determines a cell’s function
and manufactures proteins & enzymes.
DNA stores the “operating instructions” for a cell.
RNA carries out the instructions and determines cell function.
Transcription:
mRNA copies
instructions from
DNA in the nucleus
and carries them to
the synthesis site
(ribosome).
Translation:
tRNA gathers amino
acids and transports
them to the ribosome
where rRNA catalyzes
protein synthesis on
the mRNA
What if there is a copying error when DNA replicates?
Original:
The big dog bit the red fox
Base Replacement:
The big dog qit the red fox
Base Insertion:
The big dro gbi tth ere dfo x
Base Deletion:
The big dgb itt her edf ox
o
Word Insertion:
The big dog bit xyz the red fox
The big dog bxy zit the red fox
A change in the base sequences is
called a mutation.
Some mutations have no effect.
Some make subtle changes in the
organism (such as eye or hair color).
Some can make bigger changes,
most of which are harmful.
Sometimes mistakes make the story more interesting
Original:
The big dog bit the red fox
Base Replacement:
The big dog bit the red sox
Base Deletion:
Mutations cause genetic variations. Crucial for evolution.
If mutated cell survives, the mutation is
passed on to later generations (heredity)
If the mutation confers an adaptive
advantage, it gets amplified by natural
selection over many generations.
Example 1: Mutation associated with sickle
cell anemia provides resistance to malaria.
See high frequency of this condition where
there are lots of mosquitos.
Example 2: There is a specific mutation
(called CCR5-D32) in humans (a deletion
mutation) that occurs in genes associated
with T cells. It provides HIV resistance and
delays AIDS onset in people with the
mutation.
Mutation is the
molecular basis of
evolution.
A requirement of life is having a means of storing
and transmitting functional instructions (heredity).
Implications for life elsewhere:
Does life on other worlds have
analogs of DNA and RNA?
Are there other molecules that
perform this function?
NASA Origins
Longer words or more bases?
The Origin of Life on Earth
Four eons - major divisions of geological time.
Hadean: 3.85 – 4.57 Gyr ago. Before life.
Archean: 2.5 – 3.85 Gyr ago. First life.
Proterozoic: 540 Myr – 2.5 Gyr ago. First multi-celled life.
Phanerozoic: < 540 Myr ago. First animal life.
Phylogenetic tree of life
Tree of life: approximate dates
A prokaryote is a single-celled organism that
lacks a membrane-bound nucleus,
mitochondria, or any other membrane-bound
organelles.
Archaea: unicellular, with no cell nucleus. DNA contains both exons (parts of DNA that code for
proteins) and introns (junk DNA, of which we do not know the function, but it does not code for
proteins). Include extremophiles.
Bacteria also unicellular, with no cell nucleus. DNA has exons only.
Archae is fundamentally different from a Bacteria.
We do not expect the first life on Earth to be as
complex as even present-day bacteria, which has:
DNA encoding heredity and
cell function.
ATP cycle powering metabolism.
RNA-mediated protein synthesis
Wikipedia
This is a product of billions of years of
evolution!
Origin of eukaryotes?
Multiple events of endosymbiosis
The problem of how life arose from non-life is called
Abiogenesis.
Basic Requirements:
Raw Materials:
liquid H2O, CO2,
organics, phosphates
Energy Source:
Sunlight, heat, or inorganic oxidation
NOAA
Boundary to contain and organize the components
Mechanism for catalytic energy utilization (“metabolism”)
Mechanism for Reproduction and Heredity
When did life on Earth begin?
1) Fossil stromatolites (layered mats of bacteria)
can be 3.5 billion years old.
2) Microfossils of individual single-celled organisms
may also be as old as 3.5 billion years.
3) Carbon isotope ratios indicate that life existed
as long as 3.85 billion years ago.
Earliest signs of life
•
•
•
Oldest sedimentary rocks are 3.9 Ga (Greenland)
Possible signature of life in carbon isotopes?
Plants preferentially incorporate 12C over 13C. This signature is
preserved in the rock record.
First life
• First organisms were prokaryotes
• Did not require oxygen (because there was no free oxygen!)
Did life begin at ocean vents?
Source of energy and nutrients: magma
Microbes process energy through chemosynthesis (no sun light available)
Archaebacteria
• Thermoacidophiles
– Temperature > 80 oC
– pH 1-2 (more acidic than battery acid)
– Anaerobic (oxygen toxic)
– Source of nutrients and energy:
volcanoes
• Methanogens
– Anaerobic
– Use CO2, produce methane
– Found in sewage, swamps,
volcanic vents, digestive tract
The Miller-Urey experiment in 1952 showed how
amino acids could be made on the early Earth.
Mixture of H2O, methane
ammonia, H2, and CO to simulate the atmosphere.
Electric discharges to
simulate lightning.
Precipitated water as “rain”
and collected in warm liquid water “ocean”.
Quickly built up a murky
brown soup of simple amino acids and tars.
NASA
The Miller-Urey Experiment was interesting, but it
had some basic problems.
Methane & Ammonia were not
common in the primordial atmosphere
If you use CO2 and N2 you get nitrates
that destroy amino acids…
The organics that precipitated out
contained only 5 amino acids.
Made both left- and right-handed
amino acids in equal proportions.
NASA
Recent re-analysis of a second experiment using a
volcanic mixture of gases was more interesting.
Electric discharges into a
mix of volcanic gases
(H2O, CO2, H2S, etc.)
Made 22 amino acids and many other organics.
Better match to conditions
on the early Earth.
Chaiten Volcano, Chile, May 2008
Photo by Carlos Gutierrez
Complex organics & amino acids are found in some
carbon-rich meteorites.
Isotope ratios show a clearly
extraterrestrial origin.
Murchison Meteorite
The key organic compounds were
present in the early Solar System
NASA
But what about the transition…
Pre-biotic Chemistry
?
Biology?
At present, the gap from the primal 'soup' to the first RNA system capable of natural selection looks forbiddingly wide (F. Crick)
Lipid Vesicles are a natural and simple precursor for
cell membranes.
Spherical lipid membranes
self-assemble spontaneously in
liquid water (like soap bubbles).
Split into two vesicles if they grow
large enough.
Perfect containers for proto-life.
Wikipedia
Raw materials and containers, however, do not
automatically lead to life.
Two scenarios have been proposed for how non-living
organics became living organisms:
RNA World – abiotic RNA are the
precursors of life
Metabolism First – catalytic networks
for processing energy are the
precursors of life.
The RNA World model proposes that RNA-based life
(or proto-life) arose first.
RNA has useful properties:
Stores information (simple heredity)
Catalyzes its own replication
Can act like an enzyme to catalyze
reactions (“ribozymes”)
Problem is how to make RNA pre-biotically.
Simple nucleotides form in water in presence of phosphates
Clays might provide substrates to help nucleotides
polymerize into short chains.
A free-floating short strand of RNA gets enclosed in a
lipid vesicle to make a kind of “proto-cell”.
RNA in its protected vesicle
can self-duplicate from other
nucleotides.
Easiest to form a double
strand when cold.
Double strand RNA unwinds
when warmed.
External warm/cold cycles
could drive reproduction.
NASA Origins/Janet Iwasa
When vesicle grows & splits, each part carries different bits.
Final step is the emergence of DNA as the agency of
information storage and transmission.
Proteins can catalyze formation of DNA.
DNA is much more stable than RNA
and can form long double-helix chains.
More efficient and error-free replicator
than RNA.
RNA takes on a subsidiary role between
DNA and protein synthesis
DNA World: the first true prokaryotes.
Wikipedia
Metabolism First proposes that catalytic networks for
processing energy are the precursors of life.
Objection to problem of how complex
RNA molecules form abiotically.
Alternative: start with catalytic chemical
networks that can process carbon (CO2)
Oxidation of inorganics is most the likely
energy source.
Contain them within a lipid vesicle.
Wikipedia
[Robert Shapiro, NYU]
1) Lipid vesicle boundary to contain the components
2) Energy Source (oxidation of inorganic minerals)
3) Couple of energy release to a “Driver Reaction”
4) Net gain of material by the catalytic network
5) Reproduction of compartments when the vesicles split
No informational genome or heredity – yet – just “bags of stuff”
Another idea is that life arose elsewhere in the
Universe and migrated here.
Exogenesis:
Life arose elsewhere,
brought here by comets
or asteroids.
Panspermia:
“Seed of Life” are widespread through the
Universe, and seeded life on Earth.
NASA Origins
Neither idea has much support, nor does it address
the real problem of how life arises from non-life.