Molecular Mechanisms Of Genetic Variation, The Driving Force Of Biological Evolution

Werner Arber
Biozentrum, University of Basel, Switzerland

Abstract:
Spontaneous genetic variation can affect in various ways structure and availability of biological macromolecules that often represent drug targets. Here we will outline the present knowledge on molecular mechanisms of genetic variation. According to molecular Darwinism, genetic variation is the driving force of biological evolution. Mainly from studies in microbial genetics, but also from nucleotide sequence comparisons between eukaryotic organisms, we know that many different specific mechanisms contribute to the overall spontaneous generation of genetic variants. The so far studied mechanisms can be classified into three qualitatively distinct natural strategies of genetic variation: (a) local DNA sequence changes, (b) intragenomic reshuffling of DNA segments, and (c) acquisition of a DNA segment from a foreign genome. Products of so-called evolution genes thereby co-operate with a number of non-genetic elements. We can conclude that natural reality takes actively care of biological evolution. The quite low rates of genetic variation insure to the organisms a comfortable genetic stability and to the populations of organisms a steady evolutionary progress. But genetic variation is in general not directed, rather only a minority of genetic variations are favorable and provide to the organism in question a selective advantage. In contrast, one may speculate that even some silent and neutral mutations can affect drug target activities.