The origin of the fundamental metabolic pathways and the subsequent rise of the great metabolic diversity in microbes are major steps in lifes evolution on earth and, potentially, other habitable…

This is a $360,000.00 grant awarded by the National Aeronautics and Space Administration (NASA) to Michigan State University (MSU) to research the evolution of microbial metabolic networks. The research aims to understand how different metabolisms may arise and what environmental conditions select for various types of metabolic networks, particularly in the context of early microbial evolution on Earth and potentially other habitable planets. The research will combine two novel modeling approaches to explore how microbial metabolic networks evolve in dynamic competitive environments. The project has four main focuses, including developing the new evolutionary systems biology framework, applying it to the genome-scale metabolic network of Escherichia coli, understanding the evolution of nitrogen fixation in early marine cyanobacteria, and studying the evolution of simple microbial communities with competitive and mutualistic interactions. This research grant does not have a set-aside designation.

The origin of the fundamental metabolic pathways and the subsequent rise of the great metabolic diversity in microbes are major steps in lifes evolution on earth and, potentially, other habitable planets. Understanding how different metabolisms may arise and what conditions select for what types of metabolic networks is a key question for the origin of life. The evolutionary emergence of diverse metabolisms depends not only on environmental conditions but on the microbial interactions, such as competition and mutualism, as well. So far, the role of changing microbial interactions in the origin of metabolic pathways under dynamic conditions has not been investigated in detail. Here we propose to combine two novel modeling approaches from two disparate disciplines to explore how microbial metabolic networks arise and evolve in dynamic competitive environments. We will embed a recently developed metabolic modeling approach for the elementary flux mode analysis under nonequilibrium conditions (the dynamic reduction of unbalanced metabolism, drum) in an ECO-evolutionary modeling framework of trait evolution (adaptive dynamics) to investigate how different metabolic networks arise and compete in different environments. The resulting new evolutionary systems biology mathematical framework (evodrum) is a powerful tool that will allow extensive explorations of how early metabolisms appeared and were maintained by natural selection and, thus, will be useful for the field of early microbial evolution. Evodrum extends and modifies the idea of gathering the evolutionarily possible reactions by defining a large -- ideally universal -- mutation space in which evolution can proceed. In line with the adaptive dynamics framework, evolution is driven by a step by step mutant/resident invasion dynamics, with a defined mutation rate. The novelty of the proposed approach is that IT investigates the metabolically explicit trait changes and evolution as a result of selection through competitive interactions of different phenotypes. IT allows incorporating metabolic accumulation and evolutionary innovations. We will have four major foci in the proposed research. 1) we will fully develop this novel framework and apply IT to several simple metabolic networks, with several resources and temporally fluctuating conditions. In particular, we will investigate how the number of mutations, the mutation rate and neutral mutations, the concentrations of available resources and their temporal variation affect the metabolic network evolution, 2) we will apply and validate our approach on the genome-scale metabolic network of escherichia coli. We will investigate the conditions leading to the development of fermentation VS respiration strategies and the diauxic metabolic shifts and the effect of horizontal gene transfer (HGT), corresponding to the addition of big blocks of reactions, on the evolutionary outcome. We will look at the changes in modularity and connectivity in metabolic networks during evolution. 3) we will use our method to understand the evolution of nitrogen fixation in early marine cyanobacteria and their adaptation to different conditions. 4) evodrum will be used to study the evolution of simple microbial communities with competitive and mutualistic interactions, first with modified e. Coli strains, with a possibility of cross-feeding and, second, with a marine microbial consortium involving nitrogen fixers. Relevance statement. The proposed work is directly relevant to the 'early evolution of life and the biosphere' area of research in this solicitation. IT combines for the first time two distinct modeling frameworks to investigate the origin and the diversification of different metabolic pathways in microbes under changing conditions and explores how microbial interactions shape the evolution of diverse metabolisms. This work will help gain insights into the evolution of early metabolic networks in microbes and microbial interactions.