1.3 Shaping the genome: DNA mutation

Human and chimpanzee genomes are 98.8% similar. The 1.2% difference is what separates us from chimpanzees. The further you move away from human species in terms of evolutionary distance, the higher the difference gets. However, even between the members of the same species, differences in genome sequences exist. These differences are due to a process called mutation which drives differences between individuals but also provides the fuel for evolution as the source of the genetic variation. Individuals with beneficial mutations can adapt to their surroundings better than others and in time, these mutations, which are beneficial for survival, spread in the population due to a process called “natural selection”. Selection acts upon individuals with beneficial features, which gives them an edge for survival in a given environment. Genetic variation created by the mutations in individuals provides the material on which selection can act. If the selection process goes for a long time in a relatively isolated environment that requires adaptation, this population can evolve into a different species given enough time. This is the basic idea behind evolution in a nutshell, and without mutations providing the genetic variation, there would be no evolution.

Mutations in the genome occur due to multiple reasons. First, DNA replication is not an error-free process. Before a cell division, the DNA is replicated with 1 mistake per 10^8 to 10^10 base-pairs. Second, mutagens such as UV light can induce mutations on the genome. The third factor that contributes to mutation is imperfect DNA repair. Every day, any human cell suffers multiple instances of DNA damage. DNA repair enzymes are there to cope with this damage but they are also not error-free, depending on which DNA repair mechanism is used (there are multiple), mistakes will be made at varying rates.

Mutations are classified by how many bases they affect, their effect on DNA structure and gene function. By their effect on DNA structure the mutations are classified as follows:

  • Base substitution: A base is changed with another.
  • Deletion: One or more bases is deleted.
  • Insertion: New base or bases inserted into the genome.
  • Microsatellite mutation: Small insertions or deletions of small tandemly repeating DNA segments.
  • Inversion: A DNA fragment changes its orientation 180 degrees.
  • Translocation: A DNA fragment moves to another location in the genome.

Mutations can also be classified by their size as follows:

  • Point mutations: Mutations that involve one base. Substitutions, deletions and insertions are point mutations. They are also termed as single nucleotide polymorphisms (SNPs).
  • Small-scale mutations: Mutations that involve several bases.
  • Large-scale mutations: Mutations which involve larger chromosomal regions. Transposable element insertions (where a segment of the genome jumps to another region in the genome) and segmental duplications (a large region is copied multiple times in tandem) are typical large scale mutations.
  • Aneuploidies: Insertions or deletions of whole chromosomes.
  • Whole-genome polyploidies: Duplications involving whole genome.

Mutations can be classified by their effect on gene function as follows:

  • Gain-of-function mutations: A type of mutation in which the altered gene product possesses a new molecular function or a new pattern of gene expression.
  • Loss-of-function mutations: A mutation that results in reduced or abolished protein function. This is the more common type of mutation.

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