Teach Evolution

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Teach Evolution! Learn Science!
Molecular Evolution MB437 and Advances in
Molecular Evolution MB537
From the Big Bang to Bioinformatics From the
primordial soup to Bioethics
Fall, 2008, Tu/Th 11-1215 Lewis Hall 110
Who Professor Marcie McClure
mars_at_parvati.msu.montana.edu 994-7370
Text Fundamentals of Molecular Evolution by Li
and Grauer
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MOLECULAR EVOLUTION MB437 and ADVANCES IN
MOLECULAR EVOLUTION MB537 SYLLABUS Lecture 1
8/28/07 Comments. Organization
Introduction Lecture 2 8/30/07
Evolution the Big Picture Lecture 3 9/4/07
The BIG BANG and formation of the elements
necessary for life. Lecture 4 9/6/07
Biogenesis I The primitive earth and the
prebiotic soup. Lecture 5 9/11/07
Biogenesis II Self-assembly, Energetics and the
Protocell. Lecture 6 9/13/07 Biogenesis
III More on protocelluar formation. Lecture 7
9/18/07 Biogenesis IV Protein or Nucleic
Acids first? RNA or DNA? Lecture 8
9/20/07 open
discussion Lecture 9 9/25/07 The RNA world
the three Domains of life and LUCA or
LUCC. Lecture 10 9/27/07 Origin of the
Genetic Code and more on LUCC Lecture 11
10/2/07 Genomes Content and Architecture Lecture
12 10/4/07 Mutation nucleotide substitutions
and amino acid replacements. Lecture 13
10/09/07 Methods Analyzing sequences
rates/patterns. Lecture 14 10/11/07 open
discussion Lecture 15 10/16/07 Molecular
Phylogeny I History, terms, definitions, and
limits. Lecture 16 10/18/07 Molecular
Phylogeny II How to determine a phylogenetic
tree. Lecture 17 10/23/07 Molecular Phylogeny
III Improvements and Extensions to Genome
Trees. Lecture 18 10/25/07 WHATS NEW?
Bayesian and HMM Approaches to phylogenetic
reconstruction. Lecture 19 10/30/07
Deviation from Tree-like behavior horizontal
transmission of information. Lecture 20 11/1/07
mid-term II????? Lecture 21 11/6/07
Convergent Evolution the antifreeze
story. Lecture 22 11/8/07 Evolution of
Viruses. Lecture 23 11/13/07 Retroid
Agents eukaryotic hosts and disease
states. Lecture 24 11/15/07 Do viral RNA
polymerases share ancestry? Lecture 25 11/20/07
Bioethics of the Human Genome Project/
Introduction to Bioinformatics. 11/21-23/07 THA
NKSGIVING HOLIDAY Lecture 26 11/27/07 Lecture
27 11/29/07 Lecture 28 12/4/07 Lecture 29
12/6/07
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most scientists carrying out research on the
origin of life belong to one of two opposing
camps they are either metabolists or
geneticists.

Leslie Orgel
The Metabolists think that life originated
without the use of a template for replication
and this life was two dimensional in the
beginning. The Geneticists think that an
original template(s) was necessary and That life
began in a prebiotic broth.
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Last Lecture
Liposome engulfment view
Acellular metabolism on pyrite surfaces
Cell-like metabolism in iron monosulfide bubbles
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Models of self-assemblydifferent perspectives
lipid/membrane/protocell David Deamer and
colleagues
metabolic/membrane/protocell Gunter
Wachtershauser W. Martin and M
Russell Y. Koga
nucleic acid/proteins 3 different views Nielson
and Miller Eschenmoser Du Duve
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Possible Ways Bioinformational Molecules Arose
Early functional proteins replicated directly.
They invented nucleic acids and were
ultimately enslaved by them.
Early nucleic acids or related molecules
replicated directly. They invented protein
synthesis. Uncoded polypeptides may or may not
have been involved in the earliest precoding
replication mechanism.
Nucleic acid replication and genetic code of
proteins coevolved.
The first form of life on earth was based on some
inorganic or organic system unrelated to
proteins or nucleic acids.
Leslie Orgel's summation of the problem, 1987
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Ribocentric view of life
All cellular systems most DNA Viruses
Replication by RNA-dependent RNA Polymerase
McClure, 1999
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Proteins The First Bioinformational Molecules?
Yes
No

• Amino acids synthesized from
• simple compounds under prebiotic
• conditions in the same ratios as
• found on earth today.

• No complementarity no replication.

• Must invent genetic storage system.

• Amino acids can polymerize to make
• proteinoids under prebiotic conditions.
• High concentrations of proteinoids
• form vesicles and divide by budding,
• perhaps a protocell.
• Large proteinoids exhibit random
• catalytic function.

• Must invent translation.

• Even small, randomly synthesized peptides,
  exhibit function.

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Nucleic Acids The first bioinformational
molecules?
Yes
No
Ubiquity all lifeforms on earth have either DNA
or RNA as their genetic information.

• Much harder to make nucleotides under prebiotic
  conditions.
• No arbitrary ssRNA or DNA has been sythesized yet
  by any method.
• Need to invent genetic code, the initial step in
  translation.

Complementarity accounts for the replication of
all lifeforms on earth.

• Ribozymes exist catalysis sans proteins
• Elongation
• Ligation and autocatalytic replication
• cleavage

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Figure 7.2 Autocatalytic replication of an RNA
tetramer which specifically aligns with and
ligates its component dimers. (From Joyce 1987)
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Why is it hypothesized that RNA preceded DNA as
the genetic information?
RNA is primary to bioinformational exchange
Priming of synthesis for RNA and DNA
The processes of initiation, elongation and
termination for RNA are all done by one protein,
the analogous process for DNA requires much more
complex catalysis.
Storage and transfer of DNA to mRNA TX TL
Integral to the ribosome--rRNA with catalytic
activity
Integral to the splicosome in the form of
prespliced mRNA and snRNAs involved in this
process

• Deoxyribonucleotides are synthesized from ribose
  intermediates.

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Why is it thought that another informational
molecule preceded RNA?
RNA is very thermal unstable molecule.
When is RNA a stable molecule?
Double-strand
Protein coat
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The Peptide Nucleic Acid World
Stanley Miller group UCSD
Fig.1 In peptide nucleic acids, the ribose
phosphate backbone is replaced with a polyamide
backbone of N-(2-aminoethyl)glycine (AEG or ED
monoacetic acid), and the four bases are
connected through an acetic acid linker.
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The Threose Nuclaic Acid World
Eschenmoser group
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What are the Questions?
1) What was the nature of the RNA world?
2) Do fossils or descendents of the RNA world
exist?
3) How and when was RNA converted to DNA?
4) When did translation appear?
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RNARNA replication
Random base pairing
Rapid Amplification
Sloppy base pairing
Selection
Random ribo-oligo pool
Slow applification
Selection
mRNAmRNA
?
Proto-mRNA
mRNAtRNA-AA
Proto-rRNA
mRNArRNA
Proto tRNA-AA
?
Proto-translation
mRNAtRNA-AA on the rRNA
Current day life cycle of all organisms on earth
RNA Dependent Evolution
McClure 1997
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Fig.4. Phylogenetic structure analysis.
Structure models of DsrA are given for E. coli
(A) S. typhimurium (B) and K. pneumoniae (C)
Base changes relative to the E. coli sequence are
shown as white letters in a black box, and dots
indicate deletions
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Fig 5. Models of regulation. (A) DsrA shown
with the rpoS translational operator. The
structure of the rpoS translational operator (10)
is shown with the new DsrA structure model
emphasizing the integrity of stem-loop 2. The
DsrA-rpoS RNA interaction also is described
elsewhere (4,5). (B) DsrA forms a complex with
hns mRNA (Left) and with rpo5 mRNA (Right). The
hns- and rpoS-complementary regions in DsrA are
outlined in white. The start codons of hns and
rpoS (plus sign in circle) and the stop codon of
hns (minus sign in box) are shown. The DsrA-hns
RNA interaction is shown below as a coaxial
stack, with the second DsrA stem-loop melted and
the first and third stem-loops intact. In
contrast, the DsrA complex with rpoS mRNA has the
first DsrA stem-loop melted out and the second
and third stem-loops intact. Stem-loops are
numbered in circles.
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How BIG is the world of RNA genes?
tRNA 5sRNA 7sRNA scnRNAa
snRNA RNAi snoRNA
rasiRNA tasiRNA natsiRNAs
How many different functions occur in RNA genes?
XIST
piRNA
PINC
What is known about the evolution of the RNA
world?
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Ribocentric view of life
All cellular systems most DNA Viruses
Replication by RNA-dependent RNA Polymerase
McClure, 1999