Elements for a theory of molecular evolution

Biological evolution is known to be driven by the availability of genetic variants. Spontaneous genetic variation can be the result of a number of specific molecular mechanisms. These can be grouped into three qualitatively different natural strategies of generating genetic variations, namely local sequence changes, DNA rearrangement within the genome and horizontal gene transfer, which is referred to here as DNA acquisition. All of these strategies bring about alterations in the DNA sequences of the genome, thus corresponding to the molecular genetic definition of the term mutation. A detailed inspection of specific mechanisms of mutagenesis reveals on the one hand the impact of non-genetic internal and environmental factors, and on the other hand the specific involvement of gene products. The underlying so-called evolution genes can be classified into generators of genetic variations and into modulators of the frequency of genetic variation. These evolution genes are postulated to have themselves undergone biological evolution under the pressure of second-order selection. On the basis of a few selected examples of mutagenesis, elements for a theory of molecular evolution are collected without a claim for completeness. Philosophical dimensions as well as practical aspects of the advanced knowledge on specific molecular mechanisms involved in molecular evolution are also briefly discussed. (C) 2003 Elsevier B.V. All rights reserved.