Gene Mutations (AQA A-Level Biology): Revision Notes
Gene Mutations
What are gene mutations?
A gene mutation occurs when there is any alteration to one or more nucleotide bases in DNA, or when the arrangement of these bases changes. These changes can happen during DNA replication and may affect the structure and function of the proteins produced.
When mutations occur in DNA, they can alter the sequence of bases in the corresponding mRNA molecule. This change may then affect the amino acid sequence in the final polypeptide chain, potentially changing the protein's shape and function.
Types of gene mutations
Substitution mutations
Substitution involves replacing one nucleotide base with a different base in the DNA sequence. This type of mutation can have three possible outcomes:
- Formation of a stop codon: The new base creates one of the three stop codons, causing protein synthesis to end prematurely. The resulting polypeptide would be significantly shorter and almost certainly non-functional.
- Different amino acid production: The substitution creates a codon for a different amino acid, altering the polypeptide structure. This change may affect the protein's shape and prevent proper function.
- Same amino acid production: Due to the degenerative nature of the genetic code (where multiple codons can code for the same amino acid), the substitution may produce a codon that still codes for the same amino acid. In this case, the mutation has no effect on the final protein.
Real-World Example: Sickle Cell Anaemia
In sickle cell anaemia, a single base substitution in the β-globin gene changes:
- GAG (glutamic acid) → GTG (valine)
- This single amino acid change causes the haemoglobin protein to function incorrectly
- The altered protein causes red blood cells to become sickle-shaped under low oxygen conditions
Deletion mutations
Deletion occurs when a nucleotide base is lost from the DNA sequence. Although losing just one base might seem minor, the consequences can be severe.
The removal of a single base creates what is called a frame shift. Since the genetic code is read in groups of three bases (triplets), losing one base shifts the entire reading frame by one position. This means all subsequent triplets are read incorrectly, producing completely different amino acids in the polypeptide chain.
The resulting protein will have an altered amino acid sequence from the point of deletion onwards, making it non-functional and potentially harmful to the cell. A deletion near the beginning of a gene sequence can affect every amino acid that follows, while a deletion near the end has less impact but may still cause problems.
Other types of mutations
- Addition (insertion) mutations involve inserting an extra base into the DNA sequence. Like deletions, additions typically cause frame shifts that alter the entire downstream sequence of triplets. However, if three extra bases (or any multiple of three) are added, no frame shift occurs, and the resulting polypeptide will be different but may retain some function.
- Duplication mutations occur when one or more bases are repeated in the sequence. This creates a frame shift similar to addition mutations.
- Inversion mutations happen when a group of bases becomes separated from the DNA sequence and rejoins in reverse order. The base sequence of the affected portion is therefore reversed, affecting the amino acid sequence produced.
- Translocation mutations involve a group of bases becoming separated from one chromosome and inserting into a different chromosome. These mutations can seriously affect gene expression and can lead to abnormal phenotypes, including certain forms of cancer and reduced fertility.
Causes of mutations
Spontaneous mutations
Gene mutations can arise naturally during DNA replication without any external influence. These spontaneous mutations are permanent changes that occur randomly, though they happen at predictable rates. The natural mutation rate varies between species but typically ranges around one to two mutations per 100,000 genes per generation.
Mutagenic agents
External factors called mutagenic agents or mutagens can increase the rate of mutation beyond the natural level. These include:
High energy ionising radiation such as alpha and beta particles, X-rays, and ultraviolet light can disrupt DNA structure by breaking chemical bonds or causing chemical changes in the bases.
Chemical mutagens can directly alter DNA structure or interfere with DNA processes. For example, nitrogen dioxide can chemically modify DNA bases, while benzopyrene (found in tobacco smoke) is a powerful mutagen that can inactivate tumour-suppressor genes like TP53, potentially leading to cancer development.
Effects and significance of mutations
Mutations have both beneficial and harmful effects on organisms. They provide the genetic variation necessary for natural selection and evolutionary processes, creating the diversity that allows species to adapt to changing environments.
However, mutations are generally harmful and often produce organisms less well-adapted to their environment. Mutations occurring in body cells can disrupt normal cellular activities such as cell division, potentially leading to conditions like cancer.
The location where mutations occur also matters - mutations in gametes (sex cells) can be passed to offspring, while mutations in body cells only affect the individual organism.
Key Points to Remember:
- Gene mutations are changes to nucleotide bases in DNA that can alter protein structure and function
- Substitution mutations replace one base with another and may or may not affect the final protein
- Deletion mutations cause frame shifts that alter all subsequent amino acids in the polypeptide chain
- Other mutation types include addition, duplication, inversion, and translocation, each with different effects on gene expression
- Mutations occur spontaneously during DNA replication but can be increased by mutagenic agents like radiation and chemicals