Evolution of plasticity: metabolic compensation for fluctuating energy demands at the origin of life

Frank Seebacher, Julian Beaman

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


Phenotypic plasticity of physiological functions enables rapid responses to changing environments and may thereby increase the resilience of organisms to environmental change. Here, we argue that the principal hallmarks of life itself, self-replication and maintenance, are contingent on the plasticity of metabolic processes ('metabolic plasticity'). It is likely that the Last Universal Common Ancestor (LUCA), 4 billion years ago, already possessed energy-sensing molecules that could adjust energy (ATP) production to meet demand. The earliest manifestation of metabolic plasticity, switching cells from growth and storage (anabolism) to breakdown and ATP production (catabolism), coincides with the advent of Darwinian evolution. Darwinian evolution depends on reliable translation of information from information-carrying molecules, and on cell genealogy where information is accurately passed between cell generations. Both of these processes create fluctuating energy demands that necessitate metabolic plasticity to facilitate replication of genetic material and (proto)cell division. We propose that LUCA possessed rudimentary forms of these capabilities. Since LUCA, metabolic networks have increased in complexity. Generalist founder enzymes formed the basis of many derived networks, and complexity arose partly by recruiting novel pathways from the untapped pool of reactions that are present in cells but do not have current physiological functions (the so-called 'underground metabolism'). Complexity may thereby be specific to environmental contexts and phylogenetic lineages. We suggest that a Boolean network analysis could be useful to model the transition of metabolic networks over evolutionary time. Network analyses can be effective in modelling phenotypic plasticity in metabolic functions for different phylogenetic groups because they incorporate actual biochemical regulators that can be updated as new empirical insights are gained.

Original languageEnglish
Article numberjeb243214
Number of pages9
JournalThe Journal of experimental biology
Issue number5
Publication statusPublished - Mar 2022


  • Acclimation
  • Cell division
  • Environmental change
  • Metabolism
  • Network


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