The tree of life describes a tripartite cellular world

Arshan Nasir, Fizza Mughal, Gustavo Caetano-Anollés

Research output: Contribution to journalArticlepeer-review


The canonical view of a 3-domain (3D) tree of life was recently challenged by the discovery of Asgardarchaeota encoding eukaryote signature proteins (ESPs), which were treated as missing links of a 2-domain (2D) tree. Here we revisit the debate. We discuss methodological limitations of building trees with alignment-dependent approaches, which often fail to satisfactorily address the problem of ‘‘gaps.’’ In addition, most phylogenies are reconstructed unrooted, neglecting the power of direct rooting methods. Alignment-free methodologies lift most difficulties but require employing realistic evolutionary models. We argue that the discoveries of Asgards and ESPs, by themselves, do not rule out the 3D tree, which is strongly supported by comparative and evolutionary genomic analyses and vast genomic and biochemical superkingdom distinctions. Given uncertainties of retrodiction and interpretation difficulties, we conclude that the 3D view has not been falsified but instead has been strengthened by genomic analyses. In turn, the objections to the 2D model have not been lifted. The debate remains open. Also see the video abstract here:

Original languageEnglish (US)
Article number2000343
Issue number6
StatePublished - Jun 2021


  • Archaea
  • character independence
  • indels
  • origin of eukaryotes
  • phylogenetics
  • protein domains
  • root
  • tree of life

ASJC Scopus subject areas

  • General Biochemistry, Genetics and Molecular Biology


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