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

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 1.97 × 10 -5 Poliovirus 0.15 1.10 × 10 -4 Measles virus 1.00 Human Rhinovirus 9.40 × 10 -5 0.67 9.94 × 10 -5 Vesicular stomatitus virus 1.11 Murine leukemia virus 7.20 × 10 -6 0.26 4.60 × 10 -5 Rous sarcoma virus 0.43 3.20 × 10 -6 Bovine leukemia virus 0.03 HIV-1 2.10 × 10 -6 0.19 DNA MICROBES 5.4 × 10 -10 Escherichia coli 0.0025 7.8 × 10 -10 Sulfolobus acidocaldarius 0.0018 Saccharomyces cerevisiae 2.2 × 10 -10 0.0027 7.2 × 10 -10 Neurospora crasse 0.0030 H IGHER EUKARYOTES C. elegans 5.4 × 10 -10 0.018 7.8 × 10 -10 Drosophila 0.058 2.2 × 10 -10 Mouse 0.49 Human 7.2 × 10 -10 0.16 1

Mutation pressure Let µ = the mutation rate from A ⇒ a Let ν = the mutation rate from a ⇒ A Let p t = the frequency of A in the population in generation t . Let q t = the frequency of a in the population in generation t , with q t = (1 – p t ). ( ) ( ) p p 1 1 q v = − µ +         t t t 1 − − probabaili ty that A allele probabilit y that a allele did not mutate mutated to A ( ) ( ) v p p 1 1 p = − µ + − t t 1 t 1 − − v v ⎛ ⎞ t p p ( 1 v ) = + ⎜ − ⎟ − µ − ⎜ ⎟      t 0 v v µ + µ + ⎝ ⎠ As t goes to ∞ this term goes to zero Mutation pressure v v ⎛ ⎞ t goes to zero p p ( 1 v ) = + ⎜ − ⎟ − µ − ⎜ ⎟      t 0 v v µ + µ + ⎝ ⎠ As t goes to ∞ this term goes to zero When t gets very large (e.g., 10 5 or 10 6 generations) the term (1 - µ - ν ) t becomes approximately 0 v µ p ˆ ˆ = µ q = µ and Equilibrium: v v + + (regardless of initial frequencies) 2

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 ? v ˆ p = µ v + 5 8 . 9 10 − × ˆ p = 4 5 4 . 7 10 − 8 . 9 10 − × + × ˆ = p 0 . 1592 How long will it take to reach equilibrium? Mutation pressure p p ( 1 ) ( 1 p ) v = − µ + − t t 1 t 1 − − v p ˆ = µ v + It takes tens of thousands of generations to reach equilibrium 3

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 4

Pathogenicity Islands and mutational amelioration Pathogenicity Islands and mutational amelioration 5

Pathogenicity Islands and mutational amelioration AT-rich genome AT-rich genome AT-rich genome AT-rich genome 6

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? 7