Frozen Evolution. Or, that’s not the way it is, Mr. Darwin. A Farewell to Selfish Gene.

The distribution of mutations in the DNA chain is far from even.It has been found that there are long DNA sections in the individual genes in which mutations occur with very low frequency and also areas called hot spots, where mutations occur with a frequency that is several orders of magnitude greater.

            It is necessary to differentiate between two types of hot spots.In a certain experimental arrangement, it is possible to determine all the mutations that occurred in a particular gene, to be more exact in a random, more or less representative sample.In this case, the real hot spots correspond to the DNA sections in which mutations occur with greater frequency.In a different arrangement, specifically when we study the genes of individuals captured in nature, sites are found where more mutations occur and also sites where mutations are more frequently fixed or partly fixed, i.e. the original forms of the gene are replaced by a gene with a mutation in all the members of the species or population or the original form of the gene is replaced by the mutated form in a significant proportion of the individuals of the species or population.For example, this can be the areas of the genes in which it is advantageous for the population to be polymorphous or, on the other hand, the areas of the genes that are not of great biological importance and that thus can mutate almost arbitrarily without these mutants being at a disadvantage compared to the parent population.

            There can be various reasons why mutations occur more frequently at a certain site in the DNA.In the simplest case, this can be caused by the occurrence of a certain sequence motif, which assists in the formation of a certain type of mutation through some physical-chemical or biochemical mechanism.As will be mentioned in Section VI.2.2, if a tandem repetition of a DNA section exists at a certain site, it is highly probable that further multiplication of the given DNA section can occur at this site through nonreciprocal recombination.Consequently, when the same or a similar sequence of nucleotides occurs at various sites in the genome, mutation can occur at these sites through nonreciprocal recombination or gene conversion.The occurrence of two thymidines close together, in the presence of certain mutagens (e.g. UV-radiation) can lead to the formation of a thymidine dimer, whose repair can lead to a mutation.The joint occurrence of a larger amount of CG-nucleotide can again be manifested in increased frequency of mutations.A number of mutagens can cause methylation of cytosine.In vertebrates, cytosines in a large percentage of CG-dinucleotides are also methylated under normal circumstances (Colot & Rossignol 1999).Spontaneous deamination of methylated cytosine leads to its conversion to thymine and thus to mutation.In addition, some kinds of viruses or transposones are inserted into the DNA at sites where certain sequence motifs occurs.They are inserted at these sites and can generate a mutation at the given site during the processes of insertion or cutting out.  There are great differences in the frequency and type of mutations that occur in transcribed or untranscribed DNA chains in areas that are replicated in the first or later phases of replication or in areas with bonded proteins and without them (Holmquist & Filipski 1994; Francino & Ochman 1997; Alleman & Doctor 2000; Mackiewicz et al. 1999)It is thus very probable that this lack of randomness in the processes of generation and repair of mutations, i.e. mutations drive (bias) and reparations drive (VI.I), is most important from a quantitative standpoint and is simultaneously the most underestimated factor active in the evolution of genomes.

            The increased probability of the occurrence of mutations in some sequential motifs is also often of great functional importance.These motifs are often active in situations where it is advantageous for a population of organisms or population of cells to generate a greater number of mutations in certain sections of some genes.For example, it is well known that, in the hypervariable regions of immunoglobulins, serines are usually coded by AGY triplets and not synonymous TCN triplets (Y refers to any arbitrary pyrimidine, N to any arbitrary base) (Wagner, Milstein, & Neuberger 1995).This is apparently connected with the fact that the ^A/_G G  ^C/_T  ^A/_T sequence is a readily mutated sequence.s