Understanding DNA Mutations and Their Implications

mutation

Any change in the DNA base sequence

two types of mutation based on inheritance

Heritable (germ-line cell) and Transient (somatic cell)

point mutations

Mutations affecting one or a few DNA bases

examples of point mutations

Insertions, deletions, substitutions

transition mutation

Purine ↔ Purine (A ↔ G) or Pyrimidine ↔ Pyrimidine (C ↔ T)

transversion mutation

Purine ↔ Pyrimidine (A/G ↔ C/T)

examples of larger (chromosomal) mutations

Insertions (e.g. transposons), duplications, translocations, deletions

disease caused by a large chromosomal mutation

Chronic Myeloid Leukaemia - crossover in coding genes causes unregulated cell division

synonymous mutations

Silent mutations that do not change the amino acid

non-synonymous mutations

Mutations that change the amino acid sequence of a protein

frameshift mutations

Insertions or deletions that disrupt the reading frame, often due to strand looping during replication

mutagen

Any physical, chemical, or biological agent that increases the mutation rate above spontaneous levels

physical mutagens

Radiation and heat, causing double-stranded DNA breaks

chemical mutagens

Base analogs, alkylating agents, intercalating agents, deaminating agents, metal ions

biological mutagens

Viruses, bacteria, and transposons

genetic disorder highlighting the importance of DNA repair

Xeroderma Pigmentosum (XP)

cause of Xeroderma Pigmentosum

Lack of Nucleotide Excision Repair (NER) → inability to fix UV-induced thymine dimers

symptoms of XP

High UV sensitivity, thymine dimer accumulation, increased risk of skin cancer

transposable elements

Mobile DNA sequences that can move around the genome

two major classes of transposons

Class I: Retrotransposons, Class II: DNA transposons

role of the Ac and Ds elements

Ac encodes transposase; Ds requires Ac to move and can disrupt nearby genes

how transposons cause mutation

By inserting into or disrupting gene coding regions (e.g. LINE1 into APC gene)

cancer associated with transposon insertion into APC gene

Colorectal cancer

human traits evolved with help from transposons

Neurotransmission, placenta development, skin, memory, vision, starch digestion

average human germline mutation rate per base pair per generation

Approximately 1.5×10⁻⁸

new mutations in a newborn human

Around 100 new mutations

human germline mutation rate compared to other species

It is lower on a per-cell division basis

mutation rate difference between species

Mice have ~3× higher germline mutation rate than humans

mutation rate difference between cell types

Somatic cells have 10-100× higher mutation rates than germline cells

mutation rate difference between organelles

Mitochondrial DNA mutates 10-20× faster than nuclear DNA