MOLECULAR EVOLUTION MB437 and ADVANCES IN MOLECULAR EVOLUTION MB537

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MOLECULAR EVOLUTION MB437 and ADVANCES IN
MOLECULAR EVOLUTION MB537 Marcie McClure, Ph.D.
,mars_at_parvati.msu.montana.edu, 994-7370 Fall,
2006, Tu/Th 1100-1215 Cooley-B2 Lecture 1
8/29/06 Organization Introduction What is
molecular evolution? Lecture 2 8/31/06
The BIG BANG and formation of the elements
necessary for life. Lecture 3 9/5/06
Biogenesis I The primitive earth and the
prebiotic soup. Lecture 4 9/7/06
Biogenesis II Self-assembly, Energetics
and Bioinformational Molecules. Lecture 5
9/12/06 Biogenesis III Protein
or Nucleic Acids first? RNA or DNA? Lecture 6
9/14/06 The RNA world the
three Domains of life and LUCA. Lecture 7
9/19/06 Origin of the Genetic Code and more
on LUCA Lecture 8 9/21/06
Genomes Content and Architecture. Lecture 9
9/26/06 Mutation nucleotide
substitutions and amino acid replacements. Lecture
10 9/28/06 Methods Analyzing sequences
rates/patterns. Lecture 11 10/3/06
open discussion Lecture 12 10/5/06
Molecular Phylogeny I History, terms,
definitions, and limits. Lecture 13 10/10/06.
Molecular Phylogeny II How to determine a
phylogenetic tree. Lecture 14 10/12/06
Molecular Phylogeny III Improvements and
Extensions to Genome Trees. Lecture 15 10/17/06
NEW? Bayesian and HMM Approaches to
plylogenetic reconstruction Lecture 16 10/19/06
Deviation from Tree-like behavior
horizontal transmission of information Lecture 17
10/24/06 open discussion Lecture 18
10/26/06 Convergent Evolution the
antifreeze story. Lecture 19 10/31/06
Evolution of Viruses Lecture 20 11/2/06
Retroid Agents eukaryotic hosts and disease
states. Lecture 21 11/7/06 UNIVERSITY HOLIDAY
Lecture 22 11/9/06 Bioethics of the
Human Genome Project/ Introduction to
Bioinformatics. Lecture 23 11/14/06
Examples of in silico research I the RNA
polymerase story. Lecture 24 11/16/06
Examples of in silico research II the Genome
Parsing Suite finds Retroid Agents. Lecture 25
11/21/06 Protein Disorder predictions
Measles the elegance of in silico and wet
experiments 11/22-24/06 THANKSGIVING
HOLIDAY Lecture 26 11/28/06 Lecture 27
12/30/06 Lecture 28 12/5/06 Lecture 29
12/7/06
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Genic DNA informational DNA How much genic DNA
is there in the human genome? Non genic DNA
non-informational DNA junk DNA One persons
Junk is another persons information. Repetitiv
e sequences once thought to be junk are
integral to Eukaryotic genomes
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• What does the C value of an organism tell us?
• There is no correlation with inter-specific
  complexity.
• There is no correlation with intra-specific
  variation.
• These is a correlation with the amount of
  repetitive DNA.

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Retroid Agents
Retroviruses, retrotransposons,
pararetroviruses, retroposons, retroplasmids,
retrointrons, and retrons




RNA viruses e.g., Ebola, rabies, influenza, polio
All cellular systems most DNA Viruses
reverse transcriptase mediated replication or
transposition
RNA
DNA
Replication by DNA-dependent DNA polymerase
transcription
Replication by RNA-dependent RNA Polymerase
translation
snRNAs, ribozymes tRNA, rRNA

PROTEIN SYNTHESIS
McClure, 2000
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Gene Maps
Phylogenetic Tree based
Gene Maps
on 65 RT sequences
MA
C
NC
retroviruses
HIV-1
orphan class
DIRS-1
C
NC
gypsy-like retrotransposons
17.6
NC
CaMV
caulimoviruses
hepadnaviruses
HBV
NC
copia-like retrotransposons
Copia
C
LIN-H
NC
C
CIN4
C
R2Bm


NC
retroposons
C
I-FAC
INGI
introns
INT-SC1
Group II
plasmids
MAUP
retrons
MX65
TERT
1000
2000
3000
4000
RT reverse transcriptase
RH ribonuclease H

Nucleotides
H-C/IN integrase

PR aspartic acid protease
McClure, 2000
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BASIC OUTLINE OF CLASS

• 1) Speculation and research on the origin of
  life.
• 2) The RNA world as an intermediary to the DNA
  world generalities, history and current
• A) What was the RNA world like
• B) Current three domain view
• C) LUCA
• 1) RNA to DNA, David Penny
• 2) Universal Proteins Woese/Olsen, Koonin
• 3) Phylogenetics Forterre
• What is missing in talking about RNA
  gtDNAgtprotein?
• 3) Genome Content and Architecture
• A) Size and the C paradox
• B) Types of DNA
• 4) Mutation
• A) types of changes
• B) rates and patterns
• 5) Phylogenetic Reconstruction
• Complex genome analysis. What are the mechanisms
  of molecular evolution.
• The Genome Projects content and distribution
• 8) Bioinformatics

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Generalizations about mutations

• What is a mutation?
• How do we know something is a mutation?
• What is the Neutral Theory of Mutation?
• What are the classifications a of mutation?
• How is the probability of mutation measured?
• How are the number of changes between two
  nucleotide sequences counted?

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1-Dimensional Biosequence Structures
DNA TAC GGA TGT TTC GCG CTA
RNA AUG CCU ACA AAG GCG GAU
Amino acid met pro thr lys ala
asp M P T K A
D
McClure, 2001
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What is the Theory of Neutral Mutation ?

• The original hypothesis stated that all mutation
  is neutral for all practical purposes
• Kimura 1968

What is the Modified Theory of Neutral Mutation ?
Given the accumulation of sequence data Ota
hypothesized that about 10of sites are selected
for and maintained.
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What are the classification of nucleotide
substitutions?

• Transitions
• Transversions
• Synonymous/silent (s sites)
• Nonsynonymous (ns sites)
• Missense
• Nonsense

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Figure2-31 The chemical structures of the
principal bases in nucleic acids. In nucleic
acids and nucleotides, the 9 nitrogen atom of
purines and the 1 nitrogen atom of pyrimidines
are bonded to the 1 carbon of ribose or
deoxyribose.
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What about amino acid replacements?
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Strategy for Assessing Protein Sequence Homology
Protein Sequence Data
SEQUENCE COMPARISON
gt25 identical homology
lt25 identical
MOTIF DETECTION
Support for homology Statistical tests
OSM present functionally equivalent
likely homologue
Functional identification, Phylogenetic
analysis, Structural prediction
Support for homology Gene order and size,
common function
McClure, 2000
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Basic Strategy
Search Databases
Annotate and Preparation of Sequences
Multiple Alignment of Sequences
Refined Multiple Alignment
Analysis of Multiple Alignment
McClure, 2000