A model of genetic search for beneficial mutations: estimating the constructive capacities of mutagenesis

Abstract

We attempted to answer the following question: What evolutionary conditions are required to generate novel genetic modules? Our broad formulation of the problem allows us to simultaneously consider such issues as the relationship between the stage of "genetic search" and the rate of adaptive evolution; the theoretical limits to the generative capacities of spontaneous mutagenesis; and the correlation between genome organization and evolvability. We show that adaptive evolution is feasible only when the mutation rate is fine-tuned to a specific range of values and the structures of the genome and genes are optimized in a certain way. Our quantitative analysis has demonstrated that the rate of evolution of novelty depends on several parameters, such as genome size, the length of a module, the size of the adjacent nonfunctional DNA spacers, and the mutation rate at various genomic scales. We evaluated the efficiency of some mechanisms that increase evolvability: bias in the spectrum of mutation rates towards small mutations, and the availability and size of nonfunctional DNA spacers. We show that the probability of successful duplication and insertion of a copy of a functional module increases by several orders of magnitude depending on the length of the spacers flanking the module. We infer that the adaptive evolution of multicellular organisms has become feasible because of the abundance of nonfunctional DNA spacers, particularly introns, in the genome. We also discuss possible reasons underlying evolutionary retention of the mechanisms that increase evolvability.