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Mutations

Definitions

  • Mutations are changes in the genetic material of a cell or virus.

    • Genetics traditionally focuses on heritable mutations in genes

    • Molecular biology can examine ALL mutations (heritable, or not, within genes, affecting phenotype or not)

  • Genes are a genomic sequence (DNA or RNA) directly encoding functional product molecules, either RNA or protein

Background/Spontaneous mutation

Mutation is crucial for change and evolution, though the rate of spontaneous mutation is low, it is not 0.

 

  • Natural selection requires genetic differences, generated by recombination and spontaneous mutation.

  • There are approx. 200 new mutations each human child, many being de novo (new mutation appearing for the first time)

 

Mutation Origins

  • Replication/repair error

  • Food

  • Iodising radiation

  • Byproduct of life - metabolism, reactive O2 species ROS

    • A type unstable molecule containing oxygen that easily reacts with other molecules in a cell

 

Increase rate of DNA damage

  • Sunbathing

  • Holidaying in Chernobyl

 

Reducing repair efficiency

  • In bright sunlight each cell suffers 50-100 T-T dimers every second Xeroderma pigmentosum patients are unable to repair T-T dimers, making them highly susceptible to sun-induced skin cancer

 

Net Mutation

DNA damage - repair = net mutation

 

  • During replication, sometimes there can be damage to the proteins,  most of this damage is fixed, but not all, causing mutations.

  • DNA repair works to lower the net mutation rate

 

Increasing rate of

  • In bright sunlight, each skin cell suffers 50-100 T-T dimers every SECOND

    • Xeroderma pigmentosum patients are unable to repair T-T dimers, making them more susceptible to sun-induced skin cancer.

 

Germ line vs. Stoma

Germ line-cells - sperm/egg

  • 1 cell

  • Mutations are passed on to the next generation

    • Low mutation rate (-200/generation)

 

 

Somatic cells - skin

  • Genetic 'dead end'

  • Disposable to natural selection after kids

  • Essentially a mechanism to carry the germline cells

    • Higher mutation rates, though they are not passed on (10x, 100x, 1000x)

 

Effects of Mutations

The majority of mutations have no effect, due to:

 

Where they land

  • Most random mutations affect unimportant regions,

    • Between genes

    • Between exons

  • Most mutations do not chance phenotype (even if homozygous)

 

 

  • If they affect important parts (1-2% of the genome) they are:

    • Key functional residues eg.protein/RNA coding regions

    • Regulatory regions eg. Gene expression/translation signals

  • Most traits are not determined by one single mutation

  • Many genes code only for RNA, however most encode proteins

 

Mutations within protein

Point mutations consist of:

  • Silent

    • No change to protein

  • Nonsense

    • Unusually codes a stop codon

  • Missense

    • Conservative are chemically alike mutations, produce similar amino acids

    • Non-conservative are chemically not alike, produce more different amino acids

  • Frameshift

    • Insertion or deletion

 

Recessive Mutations

Majority of mutations do not effect the phenotype, those that do are recessive and only affects homozygous genotype.

 

 

  • Recessive/dominance only implies when heterozygous

  • Recessive mutations require inbreeding