VI.1 The types of mutations occurring in an organism are largely determined by mutation bias and reparation drive.
Mutations are random changes in the sequence of nucleotides that occur mainly during replication or during repair of damaged nucleic acids, in most organisms in the double-helix DNA molecule. These mutations are random in direction and in the degree of their affect on the phenotype of the organism, however not in the sites of their occurrence or in their molecular nature, i.e. whether nucleotide substitution (insertion, deletion) or inversion of part of the DNA strand occurs. As we showed in Chapter III (Mutations), the type of mutation and the probability of its occurrence at a certain position in the nucleotide strand depend not only on the nucleotide that is present in the given position, but also on the nucleotides or sequence motifs that occur around this position. However, the types and frequency of mutations are also related to the mechanism of replication of the given DNA segment. Other mutations are formed in a continuously replicated strand (leading strand) and others in a discontinuously, through Okazaki fragments, replicated strand (lagging strand) (Lobry 1996). Mutation processes are also affected by whether the given segment is, or is not, transcribed and thus whether it is present in the cell temporarily in the single-strand or more or less permanently in the double-strand form, whether it is wound around the nucleosomes or whether it is located at a site between two neighbouring nucleosomes (Francino & Ochman 1997; Tillier & Collins 2000; Szczepanik et al. 2001; Holmquist 1994).
The process of preferential formation of certain types of mutations in certain positions in the nucleotide strand is most frequently called mutation bias. In some works, this process is also called mutation pressure; nonetheless, this term should not be used in this sense, as it has long been used by geneticists and evolutionary biologists for another phenomenon that, however, occurs at the level of populations – the repeated formation of the same mutation in the population. As a large fraction of mutations occur during reparation processes, reparation drive is mostly recognized as an independent process.
It is highly probable that mutation bias and reparation drive and not, e.g., natural selection, genetic drift or genetic draft are responsible to a major degree for evolution of the overall structure of the genome, i.e. for its increase or decrease in size, changes in the content of GC pairs, formation of isochore structures and similar phenomena (Holmquist & Filipski 1994).