Cancer progression as a sequence of atavistic reversions

Charles H. Lineweaver, Kimberly J. Bussey, Anneke C. Blackburn, Paul C.W. Davies

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


It has long been recognized that cancer onset and progression represent a type of reversion to an ancestral quasi-unicellular phenotype. This general concept has been refined into the atavistic model of cancer that attempts to provide a quantitative analysis and testable predictions based on genomic data. Over the past decade, support for the multicellular-to-unicellular reversion predicted by the atavism model has come from phylostratigraphy. Here, we propose that cancer onset and progression involve more than a one-off multicellular-to-unicellular reversion, and are better described as a series of reversionary transitions. We make new predictions based on the chronology of the unicellular-eukaryote-to-multicellular-eukaryote transition. We also make new predictions based on three other evolutionary transitions that occurred in our lineage: eukaryogenesis, oxidative phosphorylation and the transition to adaptive immunity. We propose several modifications to current phylostratigraphy to improve age resolution to test these predictions. Also see the video abstract here:

Original languageEnglish (US)
Article number2000305
Issue number7
StatePublished - Jul 2021


  • Atavistic model
  • cancer
  • eukaryogenesis
  • evolution
  • phylostratigraphy
  • somatic mutation theory

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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