Causes of Gene Mutation
- Gene mutations are changes in the DNA sequence that can alter the function of a gene.
- These mutations can arise from:
- Errors in DNA replication or repair.
- External agents called mutagens.
Adenine (A) is paired with cytosine (C) instead of thymine (T).
1. Errors in DNA Replication
- During DNA replication, DNA polymerase occasionally incorporates the wrong nucleotide, resulting in mismatched base pairs.
- Most replication errors are corrected by DNA polymerase’s proofreading ability, but a small fraction escape repair, leading to permanent mutations.
Instead of pairing adenine (A) with thymine (T), DNA polymerase might pair adenine with cytosine (C).
2. Errors in DNA Repair
- DNA is constantly subjected to damage from metabolic byproducts and environmental factors.
- Repair mechanisms like base excision repair and nucleotide excision repair fix most damage, but:
- If the repair system fails or introduces errors, mutations can occur.
Faulty repair of double-strand breaks can result in deletions, duplications, or chromosomal rearrangements.
Mutagens: External Causes of Mutation
- Mutagens are agents that increase the likelihood of mutations.
- They can be classified into two main types:
- Chemical Mutagens
- Radiation
Chemical Mutagens
Chemical substances that interfere with DNA structure or function.
- Base Analogues: Molecules resembling normal DNA bases but pair incorrectly during replication.
- Alkylating Agents: Add alkyl groups to DNA bases, causing mispairing or strand breaks.
- Deaminating Agents: Remove amino groups from bases, altering their pairing properties.
- Intercalating Agents: Insert between DNA bases, distorting the helix and causing insertions or deletions.
- Students often assume that all mutations are caused by external factors, such as radiation or chemicals.
- They may overlook the fact that mutations can also arise naturally due to errors in DNA replication or repair.
Mutagenic Radiation
Forms of radiation that damage DNA, causing mutations.
- Ionizing Radiation:
- Includes X-rays, gamma rays, and alpha particles.
- These high-energy forms cause double-strand breaks, leading to deletions, translocations, or chromosomal rearrangements.
- Non-Ionizing Radiation:
- Includes UV light.
- UV radiation causes thymine dimers, where two adjacent thymine bases bond together. This disrupts normal base pairing and hinders DNA replication.
Nitrosamines can convert cytosine (C) into uracil (U), which pairs with adenine (A) instead of guanine (G).
The Combined Impact of Errors and Mutagens
- While replication errors and DNA repair failures are natural sources of mutations, exposure to mutagens amplifies the mutation rate.
- A single replication error might cause a base-pair substitution.
- UV-induced thymine dimers further hinder replication, increasing the chance of additional errors.
Real-World Implications of Gene Mutations
- Understanding the causes of gene mutations has profound implications for human health and environmental science.
- Cancer: Mutations in genes controlling cell growth and division can lead to uncontrolled proliferation, resulting in cancer.
- eg. UV-induced mutations in skin cells increase the risk of melanoma.
- Genetic Disorders: Mutations in germline cells can lead to inherited diseases like cystic fibrosis or sickle-cell anemia.
- Environmental Concerns: Pollutants like pesticides and industrial chemicals act as mutagens, increasing the mutation rate in wildlife and potentially affecting ecosystems.
- Evolution: Mutations are the raw material for evolution, providing the genetic variation needed for natural selection.
