Download Population Genetics 5: Mutation pressure Mutation pressure

Population Genetics 5:
Mutation pressure
Mutation pressure
Table 1: Estimates of per generation mutation rates for a range of organisms
Organism
Per nucleotide rate
Genomic rate
RNA GENOMES
Poliovirus
Measles virus
Human Rhinovirus
Vesicular stomatitus virus
Murine leukemia virus
Rous sarcoma virus
Bovine leukemia virus
HIV-1
1.97 × 10
-4
1.10 × 10
-5
9.40 × 10
-5
9.94 × 10
-6
7.20 × 10
-5
4.60 × 10
-6
3.20 × 10
-6
2.10 × 10
DNA MICROBES
Escherichia coli
Sulfolobus acidocaldarius
Saccharomyces cerevisiae
Neurospora crasse
5.4 × 10
-10
7.8 × 10
-10
2.2 × 10
-10
7.2 × 10
HIGHER EUKARYOTES
C. elegans
Drosophila
Mouse
Human
5.4 × 10
-10
7.8 × 10
-10
2.2 × 10
-10
7.2 × 10
-5
0.15
1.00
0.67
1.11
0.26
0.43
0.03
0.19
-10
0.0025
0.0018
0.0027
0.0030
-10
0.018
0.058
0.49
0.16
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Mutation pressure
Let µ = the mutation rate from A ⇒ a
Let ν = the mutation rate from a ⇒ A
Let pt = the frequency of A in the population in generation t.
Let qt = the frequency of a in the population in generation t, with qt = (1 – pt).
p −1 (1 − µ ) +
t

pt =
probabaility that A allele
did not mutate
qt −1 (v )

probability that a allele
mutated to A
pt = pt −1 (1 − µ ) + (1 − pt −1 )v
pt =
⎛
v
v ⎞
+ ⎜⎜ p0 −
µ − v )t
⎟(1 −

µ + v ⎝
µ + v ⎟⎠ 
As t goes to ∞
this term goes to
zero
Mutation pressure
pt =
v
v ⎞
⎛
goes to zero
+ ⎜ p −
µ − v )t
⎟(1 −

µ + v ⎜⎝ 0 µ + v ⎟⎠ 
As t goes to ∞
this term goes to
zero
When t gets very large (e.g., 105 or 106 generations)
the term (1 - µ -ν)t becomes approximately 0
Equilibrium:
pˆ =
v
µ +v
and
qˆ =
µ
µ +v
(regardless of initial frequencies)
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Mutation pressure
Example: Bacterial mutation rate (colony morphology: A ⇔ a)
A ⇒ a: 4.7 × 10-4
a ⇒ A: 8.9 × 10-5
What is the equilibrium value of A?
pˆ =
pˆ =
v
µ +v
8.9 × 10 −5
4.7 × 10 −4 + 8.9 × 10 −5
pˆ = 0.1592
How long will it take to reach equilibrium?
Mutation pressure
pt = pt −1 (1 − µ ) + (1 − pt −1 )v
pˆ =
v
µ +v
It takes tens of thousands of generations to reach equilibrium
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Pathogenicity Islands and mutational amelioration
Bacteria commonly exchange genes among their genomes:
•  lateral gene transfer (LGT) / horizontal gene transfer (HGT)
•  Heliobacter pylori
•  in one strain: 6-7% genes are unique
•  over all strains: ~20% of genes are strain specific
Bacterial genes are often moved as operons:
•  Remember operons often comprised of genes with related function
•  LGT of operons can confer novel function to a genome
•  Stretches of foreign DNA often called islands
•  pathogenicity island
•  symbiosis islands
•  metabolic islands
•  resistance islands
Pathogenicity Islands and mutational amelioration
Islands:
•  identified by anomalous GC content
•  appear as Islands of unique GC content in the genome
•  GC content of an island reflects the equilibrium state of the donor genome
•  GC of non-island DNA reflects equilibrium state of the recipient genome
Amelioration:
•  if mutation rates change the equilibrium state will change
•  if island has non-equilibrium GC content mutation pressure will cause it to evolve
to a new equilibrium.
•  process of evolution to a new GC equilibrium is called mutational amelioration
•  amelioration is much slower than in our model above because 4 states (ACGT)
•  because mutation pressure is a weak force for evolution, amelioration is slow.
•  hence, signal of LGT will persist for some time in a genome
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Pathogenicity Islands and mutational amelioration
Pathogenicity Islands and mutational amelioration
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Pathogenicity Islands and mutational amelioration
AT-rich genome
AT-rich genome
AT-rich genome
AT-rich genome
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Mutation pressure
Keynotes
•
Mutation pressure is a weak force for changing allele frequencies over the course of a
few generations, having very negligible effect on what we traditionally view as
“microevolution”.
•
As a force of evolutionary change mutation pressure is significant over thousands to
tens of thousands of generations. Note this is an example of a microevolutionary
process that gives rise to a pattern which we view as macroevolution.
•
Mutational amelioration is an example of a microevolution process that manifests itself
as a macroevolutionary pattern.
•
A stable equilibrium will be reached as long as µ and ν are unchanging.
•
A change in µ or ν results in mutation pressure for a new equilibrium.
Mutation pressure question
Contrast the statement that mutation pressure is a highly destructive
force to the genomes with the statement that mutation pressure is a
weak microevolutionary force .
Can these statements be reconciled?
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