| One of the central questions in biology is how new functions arise in the organisms' adaptation to changing environments. A well supported theory to explain the origin of genetic novelties starts from multifunctional enzymes. Through a process of gene duplication and subsequent divergence, enzymes specialize towards specific primary functions while potentially keeping some of the ancient activities as latent functions. In this project I will reconstruct the metabolism of Escherichia coli with all known latent enzymatic functions. With such a reconstruction in hand, I will use mathematical modeling to predict the evolutionary capabilities of latent functions at the systems level. Specifically, I will predict environments in which growth is possible only with latent functions. The predictions will be tested with gene overexpression experiments to increase the activity of latent functions or gene deletion experiments to show the essentiality of the latent function for growth. Furthermore, evolution experiments will be performed to investigate the role of latent functions, through mutations and selection, in adaptation to environments. The reconstruction of latent metabolism of Escherichia coli will provide knowledge about the role of promiscuous functions in network evolution at the level of the whole system and, moreover, it will pave the way for future high-throughput evolution experiments, developments of metabolic engineering and bioinformatics (software) tools. |
