DNA Mutations Notes

DNA and Genes

  • DNA is like a library in the nucleus of cells, containing thousands of books.
  • Genes are specific books containing recipes for proteins.
  • There are 23 pairs of chromosomes, which are like the bookcases of the library, where genes are located.
  • Chromosomes come in homologous pairs, one from each parent.
  • Alleles are different versions of the same genes found on homologous chromosomes.

Molecular Structure of DNA

  • DNA is composed of two strands of nucleotides.
  • A gene is a segment of this nucleotide sequence.
  • Four types of nucleotides:
    • Adenine (A)
    • Guanine (G)
    • Thymine (T)
    • Cytosine (C)

Gene Expression: Transcription and Translation

  • Gene expression involves two key processes: transcription and translation.

Transcription

  • Enzyme RNA polymerase uses a gene as a template to create messenger RNA (mRNA).
  • mRNA can leave the nucleus.
  • mRNA has the same nucleotide sequence as the gene, with uracil (U) instead of thymine (T).

Translation

  • mRNA message is encoded in codons (three nucleotides).
  • Each codon corresponds to a specific amino acid or a stop signal.
  • Ribosomes in the cytoplasm use the mRNA template to match codons with corresponding amino acids.
  • 64 different codons exist but only 20 amino acids, meaning some amino acids are encoded by multiple codons.

Mutations

  • Mutation: Alteration in the nucleotide sequence of one or more genes, potentially affecting large chromosome segments.
  • Mutations can occur in:
    • Somatic cells (any cell other than gametes)
    • Gametes (germline mutations, which can be passed to the next generation)
  • Mutations can happen spontaneously or be induced by mutagens.
  • Mutagens: Physical agents (e.g., UV rays), chemicals, or biological agents (e.g., viruses).
  • Often mutations happen during DNA replication, which happens right before a cell divides.

Small Scale Mutations

  • Small mutations involve the nucleotide sequence of a single gene:
    • Substitutions: One nucleotide is swapped for another.
    • Deletions: One or more nucleotides are deleted.
    • Insertions: One or more nucleotides are added.
Substitutions
  • The result of a substitution depends on whether the swap results in a new amino acid.
  • If a new amino acid results, the impact depends on how the new amino acid affects protein folding and function.
  • Types of substitutions:
    • Silent mutation: No change in the resulting protein.
      • Example: UGU (cysteine) mutated to UGC (cysteine).
    • Nonsense mutation: Results in a stop codon, leading to a shorter, non-functional protein.
      • Example: UGU (cysteine) mutated to UGA (stop codon).
    • Missense mutation: Results in a different amino acid.
      • Conservative: The new amino acid has similar chemical properties, so the protein can still function.
        • Example: Cysteine (polar) replaced by tyrosine (polar).
      • Non-conservative: The new amino acid has different chemical properties, impairing protein function.
        • Example: Glutamate (hydrophilic) replaced by valine (hydrophobic) in sickle cell disease, causing frail hemoglobin.
Insertions and Deletions
  • Non-Frameshift Mutation:
    • Insertions or deletions in multiples of three nucleotides.
    • Displace the reading frame of mRNA codons by exactly one entire codon.
    • Majority of the protein will have the same amino acids, with only a few added or taken away.
  • Frameshift Mutation:
    • Insertions or deletions that are not multiples of three nucleotides.
    • Shift the reading frame; every codon after the mutation is altered.
    • The entire protein is made of completely different amino acids and is often non-functional.
    • Example: Adding 'u' to UCUCCAGCU changes the amino acid sequence and protein.

Large Scale Mutations

  • Large-scale mutations: Abnormal number of chromosomes or structural abnormalities.
  • Often arise from errors during gamete formation, leading to genetic disorders.
Abnormal Number of Chromosomes
  • Aneuploidy: Additional or missing chromosomes.
    • Turner Syndrome: One X chromosome instead of two (in females) or an X and a Y (in males).
    • Down Syndrome (Trisomy 21): Extra chromosome 21.
  • Polyploidy: Extra sets of chromosomes.
    • Triploidy: Three sets of chromosomes (69 total).
    • Tetraploidy: Four sets of chromosomes (92 total).
    • Triploidy and tetraploidy are not compatible with life.
Structural Abnormalities in Chromosomes
  • Can happen because of errors in gamete formation or because of mutagens like radiation.
  • Deletion: A chunk of the chromosome goes missing.
    • Cri du chat syndrome: Deletion on the short arm of chromosome 5.
  • Duplication: Extra chunk of chromosome, often attached to the homologous chromosome.
  • Inversion: A chromosome breaks off, flips around, and reattaches.
    • Example: Gene order ABCD becomes ABDC.
  • Translocation: Part of one chromosome breaks off and is exchanged with part of a non-homologous chromosome.
    • Philadelphia chromosome: Fusion between BCR gene (chromosome 22) and ABL gene (chromosome 9), creating ABL-BCR fusion gene leading to uncontrolled cell division (leukemia).

Significance of Mutations

  • Mutations can lead to diversity, which can help species survive.
  • Genetic diversity enables evolution over time.
  • Individual uniqueness can be traced back to genetic mutations.

Recap

  • Mutations are alterations in DNA.
  • Small-scale mutations:
    • Substitutions do not alter the reading frame.
    • Insertions and deletions (not multiples of three) cause frameshift mutations.
  • Large-scale mutations:
    • Numerical abnormalities: aneuploidy (extra or missing chromosomes) and polyploidy (extra sets of chromosomes).
    • Structural abnormalities: translocation, inversion, duplication, and deletion.