Abstract
Modern enzymes are highly optimized biocatalysts that process their substrates with extreme efficiency. Many enzymes catalyze more than one reaction; however, the persistence of such ambiguities, their consequences and evolutionary causes are largely unknown. As a paradigmatic case, we study the history of bi-functionality for a time span of approximately two billion years for the sugar isomerase HisA from histidine biosynthesis. To look back in time, we computationally reconstructed and experimentally characterized three HisA predecessors. We show that these ancient enzymes catalyze not only the HisA reaction but also the isomerization of a similar substrate, which is commonly processed by the isomerase TrpF in tryptophan biosynthesis. Moreover, we found that three modern-day HisA enzymes from Proteobacteria and Thermotogae also possess low TrpF activity. We conclude that this bi-functionality was conserved for at least two billion years, most likely without any evolutionary pressure. Although not actively selected for, this trait can become advantageous in the case of a gene loss. Such exaptation is exemplified by the Actinobacteria that have lost the trpF gene but possess the bi-functional HisA homolog PriA, which adopts the roles of both HisA and TrpF. Our findings demonstrate that bi-functionality can perpetuate in the absence of selection for very long time-spans.
Highlights
Enzymes are remarkably specific catalysts and this characteristic led to the traditional view of “one enzyme, one substrate, one reaction”, which assumes an evolutionary preference for mono-functionality
To look back in time, we computationally reconstructed and experimentally characterized three HisA predecessors. We show that these ancient enzymes catalyze the HisA reaction and the isomerization of a similar substrate, which is commonly processed by the isomerase TrpF in tryptophan biosynthesis
The term exaptation describes the process by which a trait that is initially just a by-product of another function may become important in a later evolutionary phase
Summary
Enzymes are remarkably specific catalysts and this characteristic led to the traditional view of “one enzyme, one substrate, one reaction”, which assumes an evolutionary preference for mono-functionality. It is clear that enzymes can catalyze reactions other than those for which they evolved; see [1] and references therein. Multi-functional enzymes may cause metabolic conflicts if they are involved in different, possibly independent, metabolic pathways [2]. Along these lines, multi-functionality seems to be of no immediate advantage for an organism, which argues against a positive selection of this trait. Neutral drift causes the broadening or narrowing of reaction specificity, see [1] and references therein; it is unclear, whether multi-functionality is a short-term or a long-term trait
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