1 Mutation pressure Let = the mutation rate from A a Let = the - - PDF document

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Population Genetics 5: Mutation pressure

Table 1: Estimates of per generation mutation rates for a range of organisms Organism Per nucleotide rate Genomic rate RNA GENOMES Poliovirus 1.97 × 10-5 0.15 Measles virus 1.10 × 10-4 1.00 Human Rhinovirus 9.40 × 10-5 0.67 Vesicular stomatitus virus 9.94 × 10-5 1.11 Murine leukemia virus 7.20 × 10-6 0.26 Rous sarcoma virus 4.60 × 10-5 0.43 Bovine leukemia virus 3.20 × 10-6 0.03 HIV-1 2.10 × 10-6 0.19 DNA MICROBES Escherichia coli 5.4 × 10-10 0.0025 Sulfolobus acidocaldarius 7.8 × 10-10 0.0018 Saccharomyces cerevisiae 2.2 × 10-10 0.0027 Neurospora crasse 7.2 × 10-10 0.0030 HIGHER EUKARYOTES

• C. elegans

5.4 × 10-10 0.018 Drosophila 7.8 × 10-10 0.058 Mouse 2.2 × 10-10 0.49 Human 7.2 × 10-10 0.16

Mutation pressure

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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).

( ) ( )

       

A a t A t t

v q p p

to mutated allele y that probabilit 1 mutate not did allele ty that probabaili 1 1 − −

+ − = µ

( ) ( )v

p p p

t t t 1 1

1 1

− −

− + − = µ

( )

    

zero to goes term this to goes As

1

∞

− − ⎟ ⎟ ⎠ ⎞ ⎜ ⎜ ⎝ ⎛ + − + + =

t t t

v v v p v v p µ µ µ

Mutation pressure ( )

    

zero to goes term this to goes As

1

∞

− − ⎟ ⎟ ⎠ ⎞ ⎜ ⎜ ⎝ ⎛ + − + + =

t t t

v v v p v v p µ µ µ

v v p + = µ ˆ

v q + = µ µ ˆ

and

goes to zero

When t gets very large (e.g., 105 or 106 generations) the term (1 - µ -ν)t becomes approximately 0 Equilibrium: (regardless of initial frequencies)

Mutation pressure

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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? How long will it take to reach equilibrium? v v p + = µ ˆ

5 4 5

10 9 . 8 10 7 . 4 10 9 . 8 ˆ

− − −

× + × × = p

1592 . ˆ = p Mutation pressure

( ) ( )v

p p p

t t t 1 1

1 1

− −

− + − = µ

v v p + = µ ˆ

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.

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?

Mutation pressure question