Mutations

They occur all the time, most are repaired but those that aren't result in mutations. Single-base substitutions are most likely to occur when DNA is being copied (S phase for eukaryotes). In human for every cell generation there is ~150 mutations which is relatively low compared to the number of base pairs. Males contribute more mutations than females as:

~24 mitotic divisions occur from the fertilised egg that starts a female's embryonic development.

~400 mitotic divisions have occured in a 30 year old mand since the fertilized egg that formed him

Single Base Substituition (point mutation)

A single base is replaced by another base

TRANSITION: one purine (A or G) or pyrimidine (C or T) is replaced the other. Caused by Oxidative deamination or tautomerisation

TRANSVERSION: a purine is replaced by a pyrimidine or vice-versa. Caused by ionising radiation and Alkylating agents.

MISSENSE: a new nucleotide alters the codon so it changes the amino acid

NONSENSE: the changed nucleotide results in a stop codon (TAA, TAG or TGA). This prematurely stops translation of the mRNA transcribed from the mutant gene. The earlier the mutation the more likely the protein will be unable to function.

SILENT MUTATION: as most amino acids are encoded by several codons some mutations do not change the product and can only be detected by gene sequencing.

Splice site mutation
Removal of intron sequences as pre-mRNA is being processed to mRNA has to be very precise as a mutation resulting in one or more introns remaining in the mature mRNA can change the protein product. Nucleotide siganls at each intron/exon boundary guide the enzymatic machinery so if a mutation alters one of these signal then the intron is not removed and remains as part of the mature mRNA.

Insertions and deletions
One or several thousand base pair may be added or removed from a DNA sequence, collectivly they are called INDELS. They can have devistating effects as they cause a frameshift. Frameshift mutations can create new stop codons. Indels of 3 base pairs (trinucleotide repeat) or multiples may be less serious as the reading frame is preserved.

	Created by Beckie Thorne about 9 years ago

University Genetics Note on Lecture 11: Cell Cycle, DNA and mutation, created by Beckie Thorne on 05/05/2015.