III.6 Mutations can be differentiated as positive, negative and selectively neutral on the basis of their effect on the biological fitness of the organism.

According to their effect on the biological fitness, mutations can be differentiated as selectionally positive mutations (useful or also advantageous – increasing the biological fitness of their bearers), selectionally negative (detrimental or also disadvantageous – reducing the biological fitness of their bearers) and selectionally neutral (with no effect on the biological fitness of their bearers).In studying genetic drift, it was found that it is necessary to also differentiate the extremely numerous category of slightly negative mutations (see V.6).This category includes those mutations that, while they have a negative selection coefficient, this is simultaneously so low that their fate in the studied population tends to be determined by genetic drift (see Chap. V) or genetic draft (see IX.5.2) rather than by selection. Slightly positive mutations also occur, however, they are much less numerous and therefore, probably, also much less important. This differentiation is, of course, relative and is valid only in a quite specific genetic or ecological context. A mutation that is negative in a certain environment or in a particular situation can be neutral or positive under different conditions.For example, the mutation causing α–thalassemia is harmful for its host, as a large part of the haemoglobulin in the red blood cells will be present in the form of the not-very-functional homotetramers γ4 and β4.However, if an allele with this mutation occurs in persons with β–thalassemia, it prevents the formation of the poorly soluble homotatramer α4 in this person, substantially reducing the clinical manifestations of β–thalassemia and thus increasing the chances of survival for its host (Kanavakis et al. 1982; Wainscoat et al. 1983).

            The vast majority of mutations are apparently selectionally neutral and slightly negative, are not greatly reflected in the phenotype of the organism and thus, from the standpoint of natural selection, are in no way advantageous or disadvantageous for the individual.In addition, there are incomparably more negative mutations than positive mutations.There are many more ways to damage something than to improve it. Moreover, all biological structures and thus all proteins have a long period of evolution behind them, during which their biological function gradually improved through the action of natural selection.It is a certain fact that the function of no molecule is optimized to such a degree that it could not be improved by some sort of mutation.However, a great many of the possible mutations in the given molecule have already been tested during evolution and those that were found to be useful have been fixed by natural selection.Thus, for example, if a quite random change occurs in a molecule as a consequence of a quite random mutation, it is far more probable that this change will be manifested in a worsening of the biological activity of the enzyme than in its improvement (Wilhelm, Hoffmannklipp, & Heinrich 1994).It is natural selection that acts as a cunning sieve that is capable of selecting, from the enormous number of neutral and negative mutations, the very small percentage that are useful in their biological consequences.s

            From the very beginning of modern genetics, a discussion has been underway on whether positive mutations with a large or small effect are of greater importance in the evolution of adaptive structures.R.A. Fischer (Fisher 1958)and a great many others were of the opinion that mutations with a small effect are most important.They argued that mutations with a small effect have a far greater potential for shifting the relevant property of the organism in a favourable direction from the standpoint of the acting selection pressure.As a consequence of the action of mutations with a small effect, quantitative traits are shifted in a favourable direction in approximately half of cases; the action of mutations with greater effect mostly leads to shifts in an unfavourable direction, as they will act in the opposite direction in half the cases and, in a great many cases when they act in the right direction, they will “overshoot” the required optimum.In contrast, M. Kimura pointed out that, while advantageous small mutations are far more common that advantageous large mutations, nonetheless, small mutations, i.e. mutations with a low selection coefficient value, cannot have any great impact in evolution, as their fate tends to be determined more by accident than natural selection.In practice, this thus means that mutations with medium-large selection coefficients apparently have the greatest importance for the evolution of adaptive traits.While these mutations are relatively more frequently negative than mutations with low selection coefficients, if they are, however, positive, they have a far greater chance of being fixed by natural selection.

            If the mutation consists in the inactivation of a certain gene, its effect is mostly negative; however, in some cases the particular mutation need not be manifested at all, probably because of the mutual replaceability of various genes and thus, a sort of backup of vital functions.For example, in the haploid strain of the yeast Saccharomyces cerevisiae,in which 268 genes were gradually inactivated (by insertion of Tyl-transposone into the gene sequence), only slightly more than half the mutations (157) were manifested in measurable growth retardation in mutants (Smith et al. 1996).More extensive studies later showed that, of 6200 lines of haploid yeasts with deletions in the individual genes, only 1100 of them were not viable {8842}.

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The classical Darwinian theory of evolution can explain the evolution of adaptive traits only in asexual organisms. The frozen plasticity theory is much more general: It can also explain the origin and evolution of adaptive traits in both asexual and sexual organisms Read more
Draft translation from: Evoluční biologie, 2. vydání (Evolutionary biology, 2nd edition), J. Flegr, Academia Prague 2009. The translation was not done by biologist, therefore any suggestion concerning proper scientific terminology and language usage are highly welcomed. You can send your comments to flegratcesnet [dot] cz. Thank you.