Download RNA: Early Life Forms?

The Origin of Life
Take home message:
Science has not provided a step by step recipe for
making life.
Science has provided data to support some of
the possible or necessary steps.
What defines life?
1. Has a genotype (genetic blueprint that stores
and transmits information).
2. Has form and function (i.e. phenotype: expression
of genotype).
3. Life evolves.
Oparin-Haldane Model for the Origin of Life
Simple molecules
Complex polymers
H20, NH3, CO2
nucleotides, amino acids
Nucleic acid
RNA, DNA,
protein
Cellular life
RNA: Early Life Forms?
Intron in
Tetrahymena
phenotype
genotype
“Pick up the tail”
Altman and Cech
Evidence for RNA as an Early Life Form
1. Stores information and is catalytic
2. Basic component of:
a. ribosomes and tRNA
b. energy carrier molecules (ATP, GTP)
c. electron-transfer cofactors (NAD, SAM)
RNA Evolves
faster
replication
time
after a
few serial
transfers
Natural Selection
favored shorter
RNA sequences
over time, as a
consequence the
bacteriophage
became less
infectious.
Mills et al., 1967
Test Tube Experiments Show:
(1) RNA can evolve (via artificial selection)
(2) Ribozymes have been selected to perform
a number of protein-like tasks:
phosphorylation, aminoacyl transfer,
peptide bond formation, carbon-carbon
bond formation
However, can RNA self-replicate?
(i.e. can an RNA dependent replicase be found?)
But Where Did RNA Come From?
Seems unlikely that RNA can be made in one
step from inorganic molecules.
Did a self-replicating system predate RNA?
So, before RNA….
Where did simple organic molecules originate?
Did Earth Have All of the Ingredients?
Oparin-Haldane Model
Simple molecules
H20, NH3, CO2
Complex polymers
(1) Was the prebiotic
environment permissive?
nucleotides, amino acids
(2) How is this achieved in H20
given hydrolysis?
Nucleic acid
RNA, DNA,
protein
(3) How were membranes
assembled?
Cellular life
(1) Was the pre-biotic environment permissive?
Miller (1953): Assuming Atmosphere Reducing
H2, CH4, and NH3
amino acids, sugars, nucleotides
Mojzsis et al. (1999): Assuming Atmosphere Oxidizing
C02, N2:
aldehydes (ribose sugar in RNA)
Oro’ (1961): Nucleotides from inorganic molecules
HCN, NH3
adenine
(2) How is this achieved in H20
given hydrolysis?
Polynucleotides 40 nucleotides
long have been synthesized
using clay as a catalyst.
montmorillonite, illite,
and hydroxylapatite
Panspermia Hypothesis: Life originated
elsewhere and traveled to Earth.
Martian bacteria?
Murchison Meteorite
(contained amino acids)
The History of Large Impacts on Earth and It’s Moon
Moon (red)
Earth (blue)
Did meteors bring
molecules
necessary for life
to earth?
Yes, but what about
friction……
When was earth hospitable enough
for life to evolve?
Banded iron formation
Greenland 3.85 bya
magnatite
silicate
bands
Apatite crystals (20 mm)
(calcium phosphate minerals
carbonaceous
material
carbonaceous
speck with high
C12 to C13 ratio
What was the oldest common
ancestor like? (cenancestor)
a. Used DNA and amino acids to make proteins
b. Cellular
c. Structurally similar to filamentous
cyanobacteria.
Oldest known fossils
of living organisms
3.465 bya
Primaevifilum amonenum
(Schopf, 1993)
Primaevifilum conicoterminatum
Phylogeny of all living organisms
(small-subunit rRNA)
Woese (1996)
Evidence for Horizontal
Gene Transfer
Will it be possible
to reconstruct
the branching
sequence at the
root of the tree
of life?
0.85-0.9 BY
Siberia
0.59 BY China
Fossils allow estimation of
the divergence time of
eukaryotes.
1.4-1.5 BY
Australia
2 BY Eukaryotic Algae?
Michigan
Grypania spiralis
Cambrian Explosion
Evolutionary Diversification 543-506 mya
Cambrian
Explosion:
All major
body plans
first made
an appearance
in the fossil
record during
a 40 my period
Ediacaran Fuanas
entirely soft-bodied organisms from 565 mya
Brachina delicata
Spriggina floundersi
(sponges, jellyfish, comb jellies)
New Fossil Finds are Pushing Back
Estimates of Divergence Times
Fossil embryos
suggest precambrian
diversification of
bilateralians
(Xiao et al. 1998)
Possible flatworm or arthropod zygotes and embryos
Burgess Shale Faunas
520 mya
(trilobites, segmented worms, molluscs, chordates)
New Fossil Finds are Pushing Back Estimates
Of Animal Divergence Times
(Shu et al.
1999)
530 my Cambrian vertebrate: Haikouichthys eraicunensis
Small subunit RNA
most basal
earliest fossils
Cambrian: Diversification of Animal
Body Plans
Symmetry
a. Radial or asymmetrical:
Diploblast (endoderm and ectoderm)
b. Bilateral:
Triploblast (endo, ecto, and mesoderm)
Coelomate
i. Protostomes
ii.Deuterostomes
Also: segmented body plans, shells,
exoskeletons, appendages, notochords
Was the Cambrian Explosion Explosive?
Molecular clock estimates suggest 900-1200 my divergence
times for the major animal groups (Wray et al., 1996).
i.e.
Major animal lineages were established pre - Cambrian.
if so
There should be fossil evidence!
What Caused the
Cambrian Explosion?
Environmental change: Higher oxygen
may have allowed for larger, energetically
costly morphologies.
Diversification of phytoplankton may have
spurred the evolution of herbivores and
predators.
Genetic changes?
Cloudina
Stasis Is Evolution Too!
Darwin’s View
Punctuated Equilibrium
(Gould and Eldridge, 1972)
Jackson and Cheetham, 1994
Why Does Stasis Occur?
not for lack of
genetic variation
dynamic stasis
in pliocene bivalves
Extinction
Mass extinctions account for
4% of all extinctions
The big 5 of the
phanerozoic.
Iridium concentration
in clay layer at
KT Boundary
Other evidence:
• Chicxulub crater
• Microtektites
• Soot deposits
• Evidence of
tsunami
Habitat Destruction
Current extinctions are occurring at 100 - 1000 times
the normal or background rate.
May et al. 1995, Pimm et al., 1995
Human Population by 2050 = 13 billion
Evolutionary Applications in Medicine
Ch 14 - pp 529-541
Cholera Epidemic of 1854
London, England
Tuberculosis death rate as a function time
The Influenza A virus:
Responsible for global
pandemics: 1918, 1957,
1968.
Human Immune System
attacks!
antibody production
Recognizes 5 antigenic
sites on the surface of
hemagglutinin
Antigenic site: Specific parts of a foreign protein that the
immune system recognizes and remembers.
Do flu strains with novel antigenic sites enjoy a selective advantage?
Divergence of Frozen Flu Samples
Nucleotide
divergence
occurs at
a remarkably
constant
rate for
hemagglutinin.
Phylogeny of
Frozen Flu Samples
A remarkably linear
phylogenetic history.
Distribution of Amino Acid Substitutions
Antigenic Sites
Surviving Lineages
Extinct Lineages
33
31
NonAntigenic Sites
10
35
18 Codons in particular appear to be under strong Natural Selection
How is this information used to develop Flu vaccines?
Origin of Pandemic Flu Strains
Nucleoprotein
Gene
Phylogeny of flu virus hemagglutinin genes
What species did the 1968 flu likely derive?
Phylogeny of flu virus hemagglutinin genes (cont)
Hypothesis: Bird and human viruses recombine in pigs
then infect humans.
Bacteria and Antibiotics
Evidence that Antibiotics Select for Resistant Bacteria
-Possible to isolate resistant bacteria from patients that
originate during antibiotic treatment
-CDC survey (1994) data of tuberculosis patients:
New Cases
-Number with resistant bacteria
243
-Number with susceptible bacteria 2728
-Fraction resistant
8.2%
Relapsed Cases
41
150
21.5%
Frequency of penicillin resistance among Pneumococcus
bacteria in Islandic children as a function of time
Public reduced antibiotic use
Evidence that
Antibiotics
Select for
Resistant
Bacteria
Is Resistance Costly to Bacteria?
(E. coli)
Schrag et al (1997)
Yes, Costly Over the Short Term
Streptomycin-sensitive bacteria show an
increase in frequency over time.
What about the Long Term?
Not Costly Over the Long Term
Streptomycin-sensitive bacteria show a
decrease in frequency over time.
Judicious Use of Antibiotics
-Avoid contracting foodborne bacteria
-Limit use of antibacterial soaps and cleaners
-Don’t request antibiotics for colds or flu
-Take all of your antibiotic medicine
-Wash hands to avoid spread of disease
-Doctors should not prescribe antibiotics unless necessary
-Doctors should prescribe antibiotics with specific target range
-Doctors should isolate patients infected with resistant bacteria
From Levy (1998)