Evolutionary Computations and Modular Organization of the Gene Regulatory Regions

Modular organization of gene regulatory regions (promoters and enhancers) is crucial for our understanding of the gene functioning and evolution. In the area of Evolutionary Computations, inspired by the ideas and concepts from evolutionary biology, it was paid a special attention to the theoretical foundations for the evolutionary search efficacy. These were Schema theorem and Building block hypothesis (by J. Holland) that laid the foundation for this area. On the way to further develop the theory, the Royal Road functions (RRFs) were introduced and comprehensively studied. Here we are considering some case-studies of the modular gene regulatory regions which could be treated as RRFs implementations in directed molecular evolution (SELEX, etc.). Analytical tools from different math fields gave possibilities for van Nimwegen with co-authors to develop a detailed and quantitative description of the search dynamics for the RRF class of problems. The approach bridges evolutionary computations from benchmark cases, such as RRF, which are well-understood theoretically, to biological cases, which can serve as a basis for more efficient directed molecular evolution in the test tube. By introducing crossover operators that perform well on RRFs, we are developing computational techniques to deal with the real design problems for bacterial promoters. In particular, we are introducing crossover operators that work like retroviral or "sexual" PCR recombination. We found that our algorithms are capable to achieve the efficacy of the evolutionary search substantially higher than standard EC. Computational theory from EC can contribute to both understanding how real gene structures have evolved and to speeding up laboratory work on directed evolution of promoters and other gene regulatory elements.