Mutation definition
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 or not,
those affecting phenotype or not
Gene definition
A genomic sequence (DNA or RNA) which directly encodes a functional product molecule, either RNA or protein
Rate of spontaneous mutations
(Similar across all organisms but specifically in humans)
3 new mutations per 10^8 base pairs per generation
How many new/spontaneous mutations per human
200.
Mostly happen during spermatogenesis
But also after fertilisation
(Meiosis only reshuffles pre-existing genetic code)
What causes mutations
Replication/repair errors
Metabolism
Reactive oxygen species in the air (damage DNA)
Mutagens in the environment, especially in food
Ionising radiation
Net mutation rate =
Rate of DNA damage - rate of DNA repair
DNA repair is working to lower net mutation rate
Net mutation rate can be increased by
Increasing rate of DNA damage, eg sunbathing
Reducing repair efficiency, eg in sunlight 50 - 100 TT dimers are damaged per second in every skin cell
Germ line and Soma
Somatic cells are a genetic dead-end (genetics doesn’t get passed on). Higher mutation rate.
Genetic material of germ-line cells are passed on so can’t afford to mutate greatly/low mutation rate
Most mutations…
Occur in intergenic space; mutations in these regions have limited impact and do not alter phenotype (even if homozygous)
Intergenic mutations can…
Occasionally be deleterious if it occurs in
key functional residues (eg protein/RNA coding regions),
regulatory regions (control gene expression/translation signals)
Silent mutation
A mutation that has no tangible effect on the final product
Nonsense mutation
A mutation that results in the creation of a STOP codon
Missense mutation
A mutation that results in the creation of a (chemically) different product
Frameshift mutation
Insertion or deletion (INDEL) of a random number of base pairs, resulting in the production of something completely different
Recessive
Most mutations are mutations and require the individual to be homozygous for the recessive gene for it to be expressed.
Homozygous
Requires the inbreeding of heterozygous carriers
Corollary
On average a human will be a carrier for 1 - 2 recessive lethal mutations. If they have a child with a carrier/inbreed the mutation will be fatal for the resulting offspring.
