Mutation, Variation, and Gene Expression

What are the two main sources of phenotypic differences

DNA sequence - between species

Gene expression - between cell type

Fixed and lost mutations

Fixed = increase in frequency

Lost = decrease in frequency

Variants

Different versions of DNA sequences that differ by 1+ mutations

Polymorphisms

Mutations that are present in the population in a high frequency (often >1%)

Structural and regulatory mutations

Structural = change in function of a protein

Regulatory = change in expression level of a gene

Single nucleotide variants

Can be transitions (purine to purine) or transversions (purine to pyrimidine)

Tandem repeat mutations

A form of indel (insertion/deletion) occuring between tandem repeats to change copy number. Often arises due to replication slippage or homologous recombination.

Large scale mutations

Duplications, deletions, translocations, inversions, transpositions.

Suppressor mutations

A mutation that suppresses the phenotype of another mutation.

E.g. tRNA mutations

• if a codon is mutated to a stop codon, another mutation in the tRNA anticodon suppresses the original mutation.

Three ways in which small scale mutations arise

Errors during DNA replication and repair

Spontaneous chemical changes of bases that change their pairing

Induced chemical changes of bases from external mutagens

Spontaneous cytosine deamination

Cytosine undergoes deamination to become uracil, this causes C-T transition mutations.

External mutagens - Incorporation of base analogs

Base analogs are non-natural bases that can substitute for natural bases in DNA, they are mutagens if they have unusual base-pairing properties.

External mutagens - specific mis pairing

Some mutagens alter bases in ways that cause mis pairing.

External mutagens - damage that prevents pairing

Benzo[a]pyrene is a component of cigarette smoke that is converted to a mutagen that binds irreversibly to guanine.

Synonymous mutations

Don’t alter amino acid sequence

Conservative mutation

Amino acid is changed to a similar one

Regulatory mutations

Affect the level of gene expression