Mutation

Mutation = Errors in the transmission of genetic info from parents to progeny

  • The ultimate source of all genetic diversity, but comes at a cost bc most mutations are harmful

  • genetic variation in a pop is a balance between that gained by mutation and that lost by drift

  • accumulation of deleterious mutations causes inbreeding depression

  • adaptive response to change depends on genetic variation

  • another violation of HW assumptions

  • little data

  • model organisms with short gen time and large numbers

  • on a per nucleotide basis they are rare: a few per billion gametes per gen

  • from a genomic perspective they are common: genomes consist of billions of base pairs

Causes of Mutation

  • Mutagens

    • chemicals

    • Radiation: X-rays, UV light

  • Errors during DNA replication/repair

  • Transposable elements

  • Gene duplication

Process of mutation: 1) molecular mutations

  • substitutions

  • deletions

  • insertions

  • insertions and deletions are collectively called indels: can cause frameshift

2) chromosomal mutations

  • chromosomal evolution varies among taxa

    • ~100 cetacean species all with 2n=42 or 44

    • Equss: 2n varies between 32 and 66

  • Variation depends on rate of mutation and rate of incorporation into the pop

  • general mutation rate for chromosomal rearrangements 1/1000 gametes

  • Inversions

  • Recombinations

Error during Recombination

  • usually happens when homologous chromosomes are not aligned precisely by their DNA sequences

  • if not perfectly aligned, unequal crossing over occurs

  • affected region can be a single base pair or a large block of dna

  • often occurs between sequences with tandem repeats or duplicate copies of genes

  • generates a high number of copies of non-functional sequences that constitute much of the dna in most eukaryotes

Msat mutation rate high bc of unequal crossing-over and slippage

3) transposable elements

  • much of eukaryote genome consists of sequences associated with transposable elements, which can make multiple copies and inset themselves throughout the genome

  • half the human genome has sequences associated with transposable elements

  • analogous to cut and paste

  • flower color in morning glory: 9/10 mutations were transposons

  • responsible for a lot of variation in the genome

  • sometimes activated by stress

  • increase the mutation rate of host genes

4) Gene duplications

Location of the mutation

  • germ cells - gametes altered and mutation passed on to progeny

  • somatic cells - change the phenotype but only passed on in species that can reproduce without gametes

  • master control genes: regulate the expression of other genes in developmental pathways

  • cancer: genes involved in cell division and suppression of cell division

Harmful mutations (non-neutra)

  • most mutations that affect fitness are harmful

  • in small pops, drift may fix harmful alleles

  • in large pops, selection acts to keep these mutations from rising in frequency but it takes so long that new mutations occur before old mutations are eliminated

  • balance between addition of deleterious alleles and removal by selection: mutation-selection balance

  • low frequencies of deleterious alleles found in all naturally outbreeding pops: mutation load

    • important implications for inbreeding

Mutation load: Due to the selection-mutation balance, a low frequency of deleterious alleles persists in large pops

Selectively neutral mutations

  • mutation with no phenotypic effect is neutral to natural selection

    • most mutations outside of functional loci expected to be neutral

    • for neutral mutations, heterozygosity is a balance between gain from mutation and loss from drift, which depends on pop size

Can estimate pop size if mutation rate is known

  • estimated pre-whaling pop size for humpback, fin and minke whales in the N Atlantic ocean

  • pop size 6-10x higher than current estimates

  • IWC uses historical estimates of pop size to set harvest rates

  • Criticism: are estimates of mutation rate reliable?

Advantageous mutations (non-neutral)

  • drift critical in the survival of advantageous mutations even in large pops bc the allele frequency of the mutation is low

  • initial frequency is one over the total number of gene copies at a locus is q=1/2N

  • recessive mutation would have to drift to a frequency of 0.3 before even 10% of the pop will be homozygotes with the selective advantage

  • dominant mutations have a greater chance of survival bc their fitness advantage is effective in heterozygotes

    • most still lost in the first few gens due to drift

    • new mutation that increases fitness by 50%: even if individual with new mutation has 3 offspring, theres still a 0.125 chance none of the offspring carry the mutation bc of segregation

Recovery from a bottleneck

  • how rapidly do mutations add genetic diversity to pops

  • depends on mutation rate

  • equilibrium heterozygosity approached at a time scale equal to whichever is shortest: 2N or 1/2mu gens

Mutations an adaptive response?

  • commonly said to be random (but there are hotspots)

  • evidence that rate of mutations may increase under stressful conditions, creating new variation and increasing potential to adapt to changed environmental conditions

  • but probably not much help for endangered species