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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

tt vqpp

tomutatedallele y that probabilit

1

mutatenot did allele ty that probabaili

1 1 −− +−= µ

( ) ( )vppp ttt 11 11 −− −+−= µ

( )

zero togoes termthis

togoes As

0 1∞

−−⎟⎟⎠

⎞⎜⎜⎝

⎛+

−++

=t

tt v

vvp

vvp µ

µµ

Mutation pressure

( )

zero togoes termthis

togoes As

0 1∞

−−⎟⎟⎠

⎞⎜⎜⎝

⎛+

−++

=t

tt v

vvp

vvp µ

µµ

vvp+

=µ

ˆv

q+

=µµˆand

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?

vvp+

=µ

ˆ

54

5

109.8107.4109.8ˆ

−−

−

×+×

×=p

1592.0ˆ =p

Mutation pressure

( ) ( )vppp ttt 11 11 −− −+−= µ

vvp+

=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