Evolution of homology: from archetype towards a holistic concept of cell type.

The concept of homology lies in the heart of comparative biological science. The distinction between homology as structure and analogy as function has shaped the evolutionary paradigm for a century and formed the axis of comparative anatomy and embryology, which accept the identity of structure as a ground measure of relatedness. The advent of single-cell genomics overturned the classical view of cell homology by establishing a backbone regulatory identity of cell types, the basic building blocks of tissues, organs and whole organisms. This discovery provided the first objective criteria to detect the relatedness of cells regardless of their structure, function or developmental origin, which showed that the cell is the most flexible unit of living matter and that many approaches of classical biology need to be revised to understand evolution and diversity at the cellular level. The emerging theory of cell types offers a mechanistic explanation to decouple cell identity from phenotype, essentially allowing for the divergence of evolutionarily related morphotypes beyond recognition, as well as to decouple the developmental cell lineage from cell type phylogeny. This article succinctly generalises the current progress and opinion in this field and formulates a more generalistic view of biological cell types as avatars, transient or terminal cell states deployed in a continuum of states by the developmental programme of one and the same omnipotent cell that is able to change or combine identities with distinct evolutionary histories or invent ad hoc identities which never existed in evolution or development. It highlights how the new logic grounded in the regulatory nature of cellular evolution transforms the interpretation of cell type identity, its evolutionary and ontogenetic transitions, as well as elucidates the mechanisms of morphogenesis and body plan evolution, particularly in animals (Metazoa). This article is protected by copyright. All rights reserved.