Mutation



Mutations (or mutagenesis, both words originating in the Latin word mutare,
to change) are permanent, transmissible changes to the genetic material
(usually DNA or RNA) of an organism. Mutations can be caused by copying
errors in the genetic material during cell division and by exposure to
radiation, chemicals, or viruses. Mutations often lead to the malfunction or
death of a cell and can cause cancer in higher organisms. Mutations are
considered the driving force of evolution, where less favorable mutations
are removed by natural selection, but favorable ones tend to accumulate.
Neutral mutations do not affect the organism and can accumulate over time,
which might result in what is known as Punctuated Equilibrium; a modern
variation on classic evolutionary theory.

Two classes of mutations are spontaneous mutations (often called background
level) and induced mutations caused by mutagens.

Three basic types of mutations are:

  1. Point mutations are usually caused by chemicals or malfunction of DNA
     replication and exchange a single nucleotide for another. Most common
     is the transition that exchanges a purine for a purine or a pyrimidine
     for a pyrimidine (C <-> T, A <-> G). A transition can be caused by
     nitrous acid, base mispairing, or mutagenic base analogs such as
     bromouracil. Less common is a transversion, which exchanges a purine
     for a pyrimidine or a pyrimidine for a purine. A point mutation can be
     reversed by another point mutation, in which the nucleotide is changed
     back to its original state (true reversion) or by second-site reversion
     (a complementary mutation elsewhere that results in regained gene
     functionality). Point mutations are called missense or nonsense
     mutations, depending on whether the erroneous codon codes for an amino
     acid or a stop.
  2. Insertions add one or more extra nucleotides into the DNA. They are
     usually caused by transposable elements. If the number of nucleotides
     inserted is not a multiple of three, the result is a framing error.
     Insertions can be reverted by deletions.
  3. Deletions remove one or more nucleotides from the DNA. They are
     irreversible.

Spontaneous mutations on the molecular level include:

   * Tautomerism
        o Keto <-> Enol
        o Amino <-> Imino
   * Deamination ap-site (loss of A or G); occurs 1000 times each day in
     each mammal
   * Deamination base analogs (C->Uracil or A->HX); occurs 100 times each
     day in each mammal
   * Transition
   * Transversion
   * Frameshift (insertion or deletion on one strand), usually through a
     polymerase error when copying repeated sequences
   * Oxidative damage caused by oxygen radicals

Induced mutations on the molecular level can be caused by:

   * Chemicals
        o Base analogs
        o Simple chemicals, for example, acids
        o Alkylating agents
        o Polycyclic hydrocarbons, for example, the benzpyrenes found in
          internal combustion engine exhaust
        o DNA crosslinker, for example, platinum
        o Oxygen radicals
   * Radiation
        o Ultraviolet radiation
        o Ionizing radiation

DNA has so-called hotspots, where mutations occur up to 100 times more
frequently than the normal mutation rate. A hotspot can be at an unusual
base, e.g., 5'-methylcytosine.

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