Mutation and Genetic Variation Notes

Coquina Clam and Genetic Variation

• Species: Donax variabilis
• Concept: Genetic variation underpins phenotypic variation.
• Source of Variation: Novel genetic variation primarily caused by mutations.

13.2 - The Nature of Mutations

• Definition of Mutation: A heritable change in genetic material.
• Mechanisms of Inheritance:
  • Mitosis: From parental cell to daughter cells.
  • Meiosis: From parent to offspring.
  • Binary fission: From parental cell to daughter cells in prokaryotes.

How Do Mutations Come About?

• Occur due to mistakes during DNA replication, notably from DNA polymerase not correcting errors.
• Examples of DNA Damage:
  • Single-stranded break in DNA backbone
  • Cross-linked thymine bases
  • Missing base
  • Bulky side group attached to a base
  • Double-stranded break in DNA backbone
• Causes of Damage: Environmental factors such as UV radiation or chemicals (e.g., smoke).

Characteristics of Mutations

• Random Occurrence: Mutations arise randomly across the genome, not specifically connected to an organism's needs (except for rare mutational hot spots).
• Nucleotide Substitutions: Most common form of mutation; results from DNA replication mistakes.

Rates of Mutation

• General Rate: Mutation of individual nucleotides is rare, but across the genome, mutations are common.
• Analogy: Like lottery ticket holders (rare winners), mutations in individuals are rare, but occurrences in the population are common.
• DNA Polymerase Fidelity: Mutation rates differ due to fidelity differences; about 1 nucleotide in 10 billion changes during replication.

Organismal Mutation Rates

• Per Genome Per Generation: Mutation rate is significantly higher (~30 mutations per human genome per generation).
• Genomic Size and Cell Division: Larger genomes increase the chance of mutations due to more nucleotides replicated. Cell divisions before zygote formation further increase mutation potential (e.g., in males, ~400 cell divisions before producing gametes).

Mutational Risk Factors

• Males: Continuously produce gametes throughout their life, increasing mutation risk due to multiple cell divisions.
• Females: Born with all eggs, releasing 1-2 per month, resulting in fewer replication-derived mutations.

Tolerance of Mutations in Humans

• DNA Repair Mechanisms: Humans have effective DNA repair systems; most mutations affect non-coding DNA.
• Somatic vs Germ-Line Mutations:
  • Germ-line mutations are heritable and contribute to evolution by creating genetic diversity.
  • Somatic mutations impact the individual, creating mosaics of different cell lineages but not passed on to offspring.

Consequences of Mutations

• While many mutations are neutral, some can be harmful or beneficial based on their location and effect on coding sequences.
• Point Mutations: Changes affecting one nucleotide can result in:
  • Synonymous (Silent) Mutations: No effect on amino acid sequence.
  • Nonsynonymous (Missense) Mutations: Change the amino acid sequence, potential for varied effects.
  • Nonsense Mutations: Result in truncated proteins; usually harmful.

Small Insertions and Deletions (Indels)

• Indels involving several nucleotides can disrupt reading frames, affecting protein function.
• In-frame indels maintain coding integrity but may alter protein properties; out-of-frame indels cause frameshift mutations, resulting in significant changes in sequence and protein function.

Key Questions to Consider

1. What effects do point mutations have on coding sequences?
2. How do in-frame indels affect protein synthesis?
3. What happens with indels that are not multiples of three in relation to the open reading frame (ORF)?

Conclusion

• Understanding mutations is crucial for comprehending genetic diversity and mechanisms underlying evolution. Consideration of their types and impacts is vital in genetics and molecular biology studies.