Download (Part 2) Molecular evolution

BIOE 109
Summer 2009
Lecture 6- Part II
Molecular evolution
The mechanism of inheritance
circa 1865: Mendel’s work demonstrates “factors” in
pea plants that are inherited independently
from one another.
circa 1900: rediscovery of Mendel’s work
1910-1915: TH Morgan inferred existence of “genes”
and mapped their locations on chromosomes
“Classical” versus “balanced” views of
genome structure
“Classical” versus “balanced” views of
genome structure
• controversy began in the 1920’s with the establishment
of two schools of genetics.
“Classical” versus “balanced” views of
genome structure
• controversy began in the 1920’s with the establishment
of two schools of genetics.
• the “Naturalists” studied natural populations (e.g.
Dobzhansky, Mayr).
“Classical” versus “balanced” views of
genome structure
• controversy began in the 1920’s with the establishment
of two schools of genetics.
• the “Naturalists” studied natural populations (e.g.
Dobzhansky, Mayr).
• the “Mendelians” studied genetics exclusively in the
laboratory (e.g., Morgan, Sturtevant, Muller).
Classical
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-
+
+
+
+
+
+ +
+
+
Classical
+
+
-
+
+
+
+
+
+ +
+
+
+ = “wild type” allele
- = deleterious recessive allele
Classical
Balanced
+
+
-
+
+
+
A1 B2 C1 D4 E3 F6
+
+
+ +
+
+
A3 B2 C4 D5 E5 -
+ = “wild type” allele
- = deleterious recessive allele
Classical
Balanced
+
+
-
+
+
+
A1 B2 C1 D4 E3 F6
+
+
+ +
+
+
A3 B2 C4 D5 E5 -
Most loci homozygous
for wild type alleles
Most loci heterozygous
Classical
Balanced
+
+
-
+
+
+
A1 B2 C1 D4 E3 F6
+
+
+ +
+
+
A3 B2 C4 D5 E5 -
Most loci homozygous
for wild type alleles
Most loci heterozygous
Polymorphism rare
Polymorphism common
Why is this distinction important?
Classical
Balanced
Why is this distinction important?
Speciation
Classical
Balanced
Difficult
Easy
(mutationlimited)
(opportunitylimited)
Why is this distinction important?
Speciation
Selection
Classical
Balanced
Difficult
Easy
(mutationlimited)
(opportunitylimited)
Purifying
Balancing
Why is this distinction important?
Classical
Balanced
Difficult
Easy
(mutationlimited)
(opportunitylimited)
Selection
Purifying
Balancing
Population
variation
Inter > Intra
Intra > Inter
Speciation
Why is this distinction important?
Classical
Balanced
Difficult
Easy
(mutationlimited)
(opportunitylimited)
Selection
Purifying
Balancing
Population
variation
Inter > Intra
Intra > Inter
Polymorphism
transient
balanced
(short-lived)
(long-lived)
Speciation
Allozyme electrophoresis setup
Starch gel stained for
Phosphoglucomutase (Pgm)
Extensive allozyme variation exists in nature
Vertebrates
(648 species)
Extensive allozyme variation exists in nature…
…so this confirms the balanced view?
Vertebrates
(648 species)
Extensive allozyme variation exists in nature…
…so this confirms the balanced view?
Vertebrates
(648 species)
NO! MOST
POLYMORPHISMS
ARE NEUTRAL!
The neutral theory of molecular
evolution
• first proposed by Motoo Kimura in 1968.
The neutral theory of molecular
evolution
• first proposed by Motoo Kimura in 1968.
• two observations led Kimura to develop neutral
theory:
The neutral theory of molecular
evolution
• first proposed by Motoo Kimura in 1968.
• two observations led Kimura to develop neutral
theory:
1. “Excessive” amounts of protein (allozyme)
polymorphism
2. Molecular clock
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
Age 7
Age 17
Age 22
Age 46
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
• refers
to apparent constant rate of protein
evolution over large periods of time.
http://www.blackwellpublishing.com/ridley/video_gallery/LP_What_is_the_molecular_clock.asp
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
Method:
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
Method:
1. Obtain homologous amino acid sequences from a
group of taxa.
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
Method:
1. Obtain homologous amino acid sequences from a
group of taxa.
2. Estimate divergence times (from the fossil record).
2. The molecular clock
• first reported by Zuckerkandl and Pauling in 1962.
Method:
1. Obtain homologous amino acid sequences from a
group of taxa.
2. Estimate divergence times (from the fossil record).
3. Assess relationship between protein divergence and
evolutionary time.
The molecular clock
-globin gene in
vertebrates
No. of amino
acid substitutions
100
200
300
400
Time (millions of years)
500
The molecular clock ticks at different rates for
silent and replacement mutations
Kimura argued that the molecular clock
reflects the action of random drift, not
selection!
-globin gene in
vertebrates
No. of amino
acid substitutions
100
200
300
400
Time (millions of years)
500
Main features of the neutral theory
1. The rate of protein evolution is roughly
constant per site per year.
Main features of the neutral theory
1. The rate of protein evolution is roughly
constant per site per year.
- this is the "molecular clock" hypothesis.
Main features of the neutral theory
1. The rate of protein evolution is roughly
constant per site per year.
- this is the "molecular clock" hypothesis.
- per site PER YEAR, not per site PER GENERATION
Shorter generation time
Longer generation time
faster rate of molecular evolution
slower rate of molecular evolution
2. Rate of substitution of neutral alleles equals
the mutation rate to neutral alleles.
2. Rate of substitution of neutral alleles equals
the mutation rate to neutral alleles.
• this rate is unaffected by population size!
3. Rates of protein evolution vary with degree
of selective constraint.
3. Rates of protein evolution vary with degree
of selective constraint.
• “selective constraint” represents the ability of a protein to
“tolerate” random mutations.
3. Rates of protein evolution vary with degree
of selective constraint.
• “selective constraint” represents the ability of a protein to
“tolerate” random mutations.
• for highly constrained molecules, most mutations are
deleterious and few are neutral.
3. Rates of protein evolution vary with degree
of selective constraint.
• “selective constraint” represents the ability of a protein to
“tolerate” random mutations.
• for highly constrained molecules, most mutations are
deleterious and few are neutral.
• for weakly constrained molecules, more mutations are
neutral and few are deleterious.
Degree of constraint dictates rate of evolution
-globin
No. of amino
acid substitions
histone H4
100
200
300
400
Time (millions of years)
500
high constraint  low   slow rate of evolution
high constraint  low   slow rate of evolution
low constraint  high   fast rate of evolution