Biochemistry and Molecular Biology - Belyasova N.A. 2002

Molecular Foundations and Mechanisms of Heredity
Maintenance of Stability and Variability of Genomes
Mutational Process

If the DNA damage described in section 2.2 is not repaired before Replication begins, it is likely to be fixed as Mutations during the replicative doubling of DNA. In general terms, mutations can be defined as abrupt, heritable Changes in the genetic material of organisms. A distinction is made between spontaneous mutations (occurring without apparent intervention), whose frequency typically ranges from 10^-6 to 10^-8 per Cell, and induced mutations (arising in response to a mutagenic factor). The frequency of the latter depends on Organism traits, the type and dose of the mutagen, as well as Treatment conditions, and can reach up to 10^-3 per cell. Mutations can be considered the primary source of genetic variation in organisms, and along with recombination processes, they serve as a powerful driver of evolution.

To characterize the full diversity of mutational changes systematically, several Classification principles are used:

1) According to the nature of genome alteration, a distinction is made between genomic mutations (changes in chromosome number), chromosomal rearrangements (changes in Chromosome Structure leading to altered Gene number and arrangement), and Gene Mutations (changes in nucleotide sequence within a single gene, i.e., mutations in the strict sense);

2) according to their expression in the heterozygote, mutations are divided into dominant (expressed in the heterozygote) and recessive (expressed only in the homozygote);

3) according to the direction of action, mutations are subdivided into forward (altering the original or so-called wild type) and reverse (reversions), which represent a return to the wild type;

4) according to cellular localization, a distinction is made between nuclear mutations, which occur in the Chromosomes of eukaryotes and the nucleoids of prokaryotes, and cytoplasmic mutations, affecting extranuclear inheritance;

5) according to phenotypic expression, mutations are classified into lethal (leading to death), morphological (alterations in Morphology), biochemical (alterations in METABOLISM), behavioral (shifts in physiology), cryptic (having no visible phenotypic effect), resistance or sensitivity to damaging agents, and others.

Gene mutations (which are the most common), in turn, are subdivided into deletions (loss of one or more NUCLEOTIDES), transitions (replacement of Purines with purines or Pyrimidines with pyrimidines), transversions (replacement of purines with pyrimidines and vice versa), duplications (doubling of a group of nucleotides), and amplifications (multiplication of nucleotide groups). The latter two types are more characteristic of chromosomal rearrangements, where individual genes or even groups of genes are doubled or multiplied. Chromosomal mutations are also typically characterized by Transpositions (insertion of chromosome segments into new locations), translocations (exchange of segments between chromosomes), and inversions (changes in the order of genes on a chromosome).

It should be noted that mutations can lead to both loss of function and the acquisition of new traits, especially when Gene Fusion occurs and genes fall under the control of atypical regulatory elements.