A key role for centralspindlin and Ect2 in the development of multicellularity and the emergence of Metazoa

Abstract

Obligate multicellularity evolved at least five times in eukaryotes, including at the origin of Metazoa, 650-850 million years ago.^1,2,3,4 While obligate multicellularity could result from cell-cell adhesion, aggregation-based mechanisms for multicellularity are susceptible to mixing with genetically unrelated cells.⁵ Alternatively, or in addition, multicellularity can emerge from a series of mitotic divisions followed by incomplete cytokinesis, resulting in a cluster of cells connected by intercellular bridges.^6,7,8,9,10 In addition to being multicellular, all five clades of extant Metazoa are diploid organisms that reproduce via eggs and sperm (anisogamy).^7,11,12,13 Thus, by inference, the last common ancestor (LCA) of Metazoa could produce sperm and eggs and could cleave fertilized eggs into smaller cells that self-organize into fertile organisms¹⁴-processes that directly involve the cytokinetic machinery. Here, I present an integrated analysis into the emergence of three regulators of cytokinesis. Phylogenetic analysis and structural modeling indicate that Kif23, Cyk4, and Ect2 are highly conserved across all metazoans. These proteins cooperate to link the plane of cell division with the position of the spindle during anaphase and subsequently nucleate the assembly of stable intercellular bridges,^15,16,17,18 structures prevalent in metazoan germ lines.⁷ The closest relatives of Metazoa, Choanoflagellata, encode orthologs of Kif23 and Ect2. Choanoflagellate species variably encode proteins homologous to Cyk4, a subset of which are predicted to interact with Kif23. These findings, in light of prior knowledge, suggest that the evolutionary refinement of these three cytokinetic regulators was a proximal prerequisite for the evolution of defining features of Metazoa.

Keywords: animal evolution; cell division; centralspindlin; cytokinesis; incomplete cytokinesis; metazoa; multicellularity.