ArticleBioinformatics (Oxford, England)2018
Understanding the evolution of functional redundancy in metabolic networks.
Article in Bioinformatics (Oxford, England), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 1 of them a synthesis that pooled it.
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Who cites it
21 citing papers in PubMed, 1 synthesis or guideline pooled it.
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- Nicotinamide mononucleotide combined with PJ-34 protects microglial cells from lipopolysaccharide-induced mitochondrial impairment through NMNAT3-PARP1 axis.Journal of translational medicine · 2025Article
- Proteomic analyses reveal the key role of gene co-option in the evolution of the scaly-foot snail scleritome.Communications biology · 2025Article
- Understanding flux switching in metabolic networks through an analysis of synthetic lethals.NPJ systems biology and applications · 2024Article
- The unique catalytic properties of PSAT1 mediate metabolic adaptation to glutamine blockade.Nature metabolism · 2024Article
- Differential Regulation of Opsin Gene Expression in Response to Internal and External Stimuli.Genome biology and evolution · 2024Article
- Exploring Emergent Properties in Enzymatic Reaction Networks: Design and Control of Dynamic Functional Systems.Chemical reviews · 2024Review
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- Identification of risk genes for Alzheimer's disease by gene embedding.Cell genomics · 2022Article
- Genetic Context Significantly Influences the Maintenance and Evolution of Degenerate Pathways.Genome biology and evolution · 2021Article
- Identifying "more equal than others" edges in diverse biochemical networks.Proceedings of the National Academy of Sciences of the United States of America · 2021Article
- Construction, comparison and evolution of networks in life sciences and other disciplines.Journal of the Royal Society, Interface · 2020Article
- Mechanisms of tissue and cell-type specificity in heritable traits and diseases.Nature reviews. Genetics · 2020Review
- Investigating metabolic interactions in a microbial co-culture through integrated modelling and experiments.Computational and structural biotechnology journal · 2020Article
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Motivation: Metabolic networks have evolved to reduce the disruption of key metabolic pathways by the establishment of redundant genes/reactions. Synthetic lethals in metabolic networks provide a window to study these functional redundancies. While synthetic lethals have been previously studied in different organisms, there has been no study on how the synthetic lethals are shaped during adaptation/evolution. Results: To understand the adaptive functional redundancies that exist in metabolic networks, we here explore a vast space of 'random' metabolic networks evolved on a glucose environment. We examine essential and synthetic lethal reactions in these random metabolic networks, evaluating over 39 billion phenotypes using an efficient algorithm previously developed in our lab, Fast-SL. We establish that nature tends to harbour higher levels of functional redundancies compared with random networks. We then examined the propensity for different reactions to compensate for one another and show that certain key metabolic reactions that are necessary for growth in a particular growth medium show much higher redundancies, and can partner with hundreds of different reactions across the metabolic networks that we studied. We also observe that certain redundancies are unique to environments while some others are observed in all environments. Interestingly, we observe that even very diverse reactions, such as those belonging to distant pathways, show synthetic lethality, illustrating the distributed nature of robustness in metabolism. Our study paves the way for understanding the evolution of redundancy in metabolic networks, and sheds light on the varied compensation mechanisms that serve to enhance robustness. Supplementary information: Supplementary data are available at Bioinformatics online.
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