The per generation mutation rate varies across the tree of life by orders…
The per generation mutation rate varies across the tree of life by orders of magnitude
2. Disparity between mutation rate-genome size correlations across taxa
Drake: mutation rate is constant across all microbial life (-0.003 rule)
cost of repair hypothesis.
Lynch opposes: total cost of genome replication is low energetically; rates of dna replication faster than mRNA. No evidence that this poses as limitation.
Observe: mutation rates scale positively with genome size in eukaryotes.
although limited coverage of taxa, Lynch's finding supports his conjecture to some extent. Drake's rule hold for a subset of microbial species.
Observe: mutation rate inversely correlated genome size in microbial species.
Generation-time hypothesis: groups with shorter generations evolve faster, more rounds of divisions; more DNA synthesis and opportunities for mutations
experiment: in bacteria, cell division times are either unchanged or decline with increasing genome size.
1. Most mutations are either deleterious or neutral
mutation rate fined-tuned by adaptation
Orr2000: population should evolve mutation rate that maximizes rate of adaptation which depends solely on the strength of selection which implies that mutation rate is independent of population size.
observe: evolved mutation rate in microorganisms is 100- to 1000- fold lower than in vertebrates
evolving high mutation rate without high mutational load
restricting high mutation rate to times when adaptive genotype is required under environmental stress
observe: stress-induced mutagenesis in microorganisms to provide transient mechanisms for generating adaptive genotype in extreme environment.
restricting high mutation rate to certain loci, thus confining deleterious mutations to a small fraction of the genome.
observe: within genome variation.
mutation should evolve toward zero
Kimura: physiological cost to reducing mutation rate, lower limit = cost of repair and cost of fidelity.
observe: eukaryotes appears to have narrow range of mutation rate (lower limit)
mutation rate observed is the optimal mutation rate determined by a trade off between costs of high mutation rate and metabolic costs of maintaining systems to reduce mutation rate.
3. Mutation rate correlates with effective population size
Lynch suggested that mutation rate pattern across species indirect result of effective population size. Estimated from levels of standing variation at silent sites.
In opposition to Kimura's physiological limits hypothesis, Lynch argues that lower bound on the mutation rate is due to natural selection's inability to push the rate any lower.
He then proposes the drift barrier hypothesis: random genetic drift constrains the lower limit of mutation rate as selective advantage improvement becomes neutral
deleterious mutation rate is expected to scale inversely with the effective population size.
increase in selection efficiency leads to proportional reduction in the evolved mutation rate.
observe: thermophiles have low mutation rates, average effect of deleterious mutation increases (due to greater selective efficiency).
As mutation rates becomes a function of selective coefficient. this is consistent with previous theories linking mutation rates and fitness.
Genetic duplication and Genetic robustness
under the assumption that nt diversity at silent sites is effectively neutral, significant negative correlation between mutation and effective population size.
observe buchnera aphidicola, reduced genome size and high mutation rate.
4. Modifiers of mutation rates
Lynch: mutation rate is dependent on the relative rates at which mutator and antimutator alleles arise.
various models of evolution have been used to demonstrate processes that increase and reduce mutation rates. Taddel: mutator genes accelerating adaptive evolution. Reversion of mutator allele, compensatory evolution and horizontal genetic exchange. Hitchhiking and recombination.
Error prone polymerases
observe: the genomes of nearly all organisms encode for error prone polymerases.
Foster: property promoted by natural selection as means for generating adaptive mutations.
Gerrish experiments provided evidence that this supposedly magnifies background production of deleterious mutations, and thus can ultimately lead to long-term genomic deterioration.
'Use it or lose it' hypothesis: consistent with observation that less frequently used polymerases naturally evolve higher error rates.
5. Mutation rate variation between genomes
Somatic vs germline mutations
observe: germline mutations is much lower than somatic mutations.
experiment in mice
selection operates on the per-generation mutation rate, accommodated by changes in replication fidelity at the cell division level.
observe: mitochondrial DNA most popular marker of molecular diversity, elevated mutation rate
metabolic rate hypothesis: higher metabolic rates produce more free radicals, which leads to greater DNA damage and faster mutation.
6. Other observations
Variation in nucleotide substitution
Topological features affecting mutation rates
Gene expression associated with mutational vulnerability
Transcription and translation infidelity