Scaling laws in enzyme function reveal a new kind of biochemical universality

Dylan C. Gagler, Bradley Karas, Christopher P. Kempes, John Malloy, Veronica Mierzejewski, Aaron D. Goldman, Hyunju Kim, Sara I. Walker

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


All life on Earth is unified by its use of a shared set of component chemical compounds and reactions, providing a detailed model for universal biochemistry. However, this notion of universality is specific to known biochemistry and does not allow quantitative predictions about examples not yet observed. Here, we introduce a more generalizable concept of biochemical universality that is more akin to the kind of universality found in physics. Using annotated genomic datasets including an ensemble of 11,955 metagenomes, 1,282 archaea, 11,759 bacteria, and 200 eukaryotic taxa, we show how enzyme functions form universality classes with common scaling behavior in their relative abundances across the datasets. We verify that these scaling laws are not explained by the presence of compounds, reactions, and enzyme functions shared across known examples of life. We demonstrate how these scaling laws can be used as a tool for inferring properties of ancient life by comparing their predictions with a consensus model for the last universal common ancestor (LUCA). We also illustrate how network analyses shed light on the functional principles underlying the observed scaling behaviors. Together, our results establish the existence of a new kind of biochemical universality, independent of the details of life on Earth’s component chemistry, with implications for guiding our search for missing biochemical diversity on Earth or for biochemistries that might deviate from the exact chemical makeup of life as we know it, such as at the origins of life, in alien environments, or in the design of synthetic life.

Original languageEnglish (US)
Article numbere2106655119
JournalProceedings of the National Academy of Sciences of the United States of America
Issue number9
StatePublished - Mar 1 2022


  • Astrobiology
  • Biochemical networks
  • Enzymes
  • Scaling laws
  • Statistical physics

ASJC Scopus subject areas

  • General


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