The role of cellular objectives and selective pressures in metabolic pathway evolution

Abstract

Evolution results from molecular-level changes in an organism, thereby producing novel phenotypes and, eventually novel species. However, changes in a single gene can lead to significant changes in biomolecular networks through the gain and loss of many molecular interactions. Thus, significant insights into microbial evolution have been gained through the analysis and comparison of reconstructed metabolic networks. However, challenges remain from reconstruction incompleteness and the inability to experiment with evolution on the timescale necessary for new species to arise. Despite these challenges, experimental laboratory evolution of microbes has provided some insights into the cellular objectives underlying evolution, under the constraints of nutrient availability and the use of mechanisms that protect cells from extreme conditions.

Figure 1. Cellular objectives and selective pressures guiding pathway evolution

Theoretical (a,b) and experimental (c,d) approaches have been used to gain insight into how the interactions between cellular objectives and selective pressures guide the evolution of metabolic pathways. Specifically, these efforts have shown how (a) microbes gain and lose pathways with an objective to gain biomass under the pressure of limited nutritional resources, and that (c) the metabolic pathways used are consistent with the in silico-predicted optimal pathways. In addition, cells also have an indirect objective of self-protection against a selective pressure of stressful environmental conditions. Consistent with this, (b) adaptation to different temperatures correlates with topological changes in metabolic pathways, and (d) microbes evolve mechanisms to metabolize or protect against toxic environmental conditions.

Figure 2. Extension of metabolic pathways through laboratory evolution

Laboratory evolution under a defined selective pressure has identified a few cases in which a new metabolic function arose. Three of these examples include the ability that E. coli gained to (a) transport citrate after 33,000 generations, (b) metabolize L-1,2-propanediol and ethylene glycol, and (c) synthesize glutathione when a key enzyme in its synthesis was deleted.

Figure 3. Two models of pathway evolution

(a) The retrograde model suggests that duplication events of neighboring genes extends pathways from a key metabolite. (b) The patchwork model assumes novel pathways arise as broad-specificity enzymes are acquired or duplicated and mutated, thus forming a new pathway. Dashed grey arrows represent duplication events and mutation.