Mutations

• A mutation is any heritable change in the genetic material

  • “Heritable” means that the mutation is stable and is therefore passed on through cell division
• RNAs are not heritable; many copies of RNA are produced and a single bad one is not a big problem to the organism .... it’s a different story with DNA
• Spontaneous and random mutations occur all the time during DNA replication that can alter the nucleotide sequence, and environmental influences can cause mutations by damaging DNA.
• Mutations can be harmful, beneficial, or have a neutral effect
• Passing on a mutation can happen at different levels, depending on cell type

  • In single-celled organisms, mutations are passed on to future generations
• Passing on a mutation can happen atdifferent levels, depending on cell type

  • In multicellular organisms, somatic (non-reproductive) mutations are passed only to the daughter cells in that organism and are not transferred to future generations of the organism.
• Passing on a mutation can happen at different levels, depending on cell type

  • Mutations in germ cells (reproductive) are passed to future generations
• Small scale mutations: Point mutations

  • Changes in a single nucleotide
  • Synonymous, Non-synonymous, and nonsense mutations
• Sometimes, a nucleotide change in DNA doesn’t change amino acid it codes for (or changes it to one w/ similar properties)

  • In this case, the protein will still fold – and thus function – properly.
  • This is called a synonymous mutation
• Other point mutations can end up changing amino acid downstream to one with totally different properties

  • This usually causes the protein to folding correctly, preventing it from performing its function properly
  • This is a nonsynonymous or missense mutation
• If the point mutation changes an amino acid codon to a STOP codon, this is a “nonsense” mutation
• Nonsense mutation

  • When the stop codon is encountered, translation stops prematurely, resulting in a truncated polypeptide.
  • Nearly all truncated proteins are nonfunctional and unstable
• Small scale: Insertions or deletions

  • Small insertions or deletions can involve several nucleotides.
  • Frameshift and in-frame mutations
• In-frame insertions/deletions can also be harmful

  • A small deletion or insertion that is an exact multiple of three nucleotides results in a polypeptide with as many fewer or more amino acids as there are codons deleted or inserted
• In-Frame mutations

  • A deletion of three nucleotides eliminates one amino acid.
  • An insertion of six nucleotides adds two amino acids.
• A technique called gel electrophoresis can be used to compare the sizes of nonmutant and mutant DNA, mRNA and protein molecules
• gel electrophoresis

  • Separate molecules by size
  • Smaller molecules move more quickly towards the bottom of gel than larger ones
• Some mutations, however, can be more large-scale, affecting thousands or millions of nucleotides

  • Happen at chromosomal level
• A chromosome is simply how DNA is organized in the nucleus

  • Chromosome = DNA + proteins that coil it up into neat little clusters
• When a chromosome is mutated, huge chunks of DNA might be....

  1. Swapped between different chromosomes
  2. Flipped backwards
  3. Duplicated or deleted