The tree of life describes a tripartite cellular world

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 here: https://youtu.be/-6TBN0bubI8 Exploring deep evolutionary history with a Tree of Life requires that conclusions from comparative genomics and phylogenomic reconstruction be mutually reinforcing. Only then can historical interpretations that have high explanatory power be proposed. Here we claim that the 3‐domain tree of life describing the cellular world continues to withstand refutation.