Abstract
Metabolic networks perform some of the most fundamental functions in living cells, including energy transduction and building block biosynthesis. While these are the best characterized networks in living systems, understanding their evolutionary history and complex wiring constitutes one of the most fascinating open questions in biology, intimately related to the enigma of life's origin itself. Is the evolution of metabolism subject to general principles, beyond the unpredictable accumulation of multiple historical accidents? Here we search for such principles by applying to an artificial chemical universe some of the methodologies developed for the study of genome scale models of cellular metabolism. In particular, we use metabolic flux constraint-based models to exhaustively search for artificial chemistry pathways that can optimally perform an array of elementary metabolic functions. Despite the simplicity of the model employed, we find that the ensuing pathways display a surprisingly rich set of properties, including the existence of autocatalytic cycles and hierarchical modules, the appearance of universally preferable metabolites and reactions, and a logarithmic trend of pathway length as a function of input/output molecule size. Some of these properties can be derived analytically, borrowing methods previously used in cryptography. In addition, by mapping biochemical networks onto a simplified carbon atom reaction backbone, we find that properties similar to those predicted for the artificial chemistry hold also for real metabolic networks. These findings suggest that optimality principles and arithmetic simplicity might lie beneath some aspects of biochemical complexity.
Highlights
The prominent role of metabolism in any biological process and the fact that a large portion of the environmental factors shaping living systems are metabolic in nature, suggest that strong selective forces have been acting on metabolic networks throughout the history of life
Metabolism is the network of biochemical reactions that transforms available resources (‘‘inputs’’) into energy currency and building blocks (‘‘outputs’’)
We find that optimal pathways in our idealized chemistry display a logarithmic dependence of pathway length on input/output molecule size
Summary
The prominent role of metabolism in any biological process and the fact that a large portion of the environmental factors shaping living systems are metabolic in nature, suggest that strong selective forces have been acting on metabolic networks throughout the history of life. Especially during major transitions, such as the early stages of life’s appearance or the rise of oxygen in the Earth’s atmosphere, selective forces must have shaped the metabolic wiring itself [4]. Comparative genomics can provide top-down insight into some long-term evolution of metabolic pathways [5,6]. Whether the long term evolution of metabolism was dominated by unpredictable frozen accidents, or by inevitable network optimization processes, remains a fundamental open question
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
