Choanoflagellates, sponges and other metazoans last shared a unicellular common ancestor in the late Precambrian period, more than 600 million years ago41,42
. Although the origin of metazoans was a pivotal event in life’s history, little is known about the genetic underpinnings of the requisite transition to multicellularity. Comparisons of modern genomes provide our most direct insights into the ancient genomic conditions from which metazoans emerged. By comparing choanoflagellate and metazoan genomes, we infer that their common ancestor had intron-rich genes, some of which encoded protein domains characteristically associated with cell adhesion and the ECM in animals.
In addition to containing protein domains associated with metazoan cell adhesion, M. brevicollis possesses a surprising abundance of tyrosine kinases and their downstream signalling targets. In contrast, components of most other intercellular signalling pathways, as well as many of the diverse transcription factors that comprise the developmental toolkit of modern animals, are absent. These presumably reached their modern form on the metazoan stem, although it is formally possible that they were in place much earlier and degenerated in the M. brevicollis lineage. Likewise, it is possible that the last common ancestor of choanoflagellates and metazoans had an early form of multicellularity that became more robust in metazoans and was lost in the choanoflagellate lineage. In any event, the evolutionary distance between choanoflagellates and metazoans is substantial, and evidently few, if any, intermediate lineages survived. There are, for example, no other known microbial eukaryotes that possess any of the eight developmental signalling pathways characteristic of metazoans.
The mechanism of invention of new genes on the metazoan stem, and their integration to create the emergent network of cell signalling and transcriptional regulation fundamental to metazoan biology, remains mysterious. Domain shuffling, which has frequently been proposed as an important mechanism for the evolution of metazoan multidomain proteins43,44
, is implicated by the presence of essential metazoan signalling domains in M. brevicollis
that appear in unique combinations relative to animals. For pTyr-based signalling in particular, the marked divergence of domain combinations suggests that this mode of cellular interaction existed in a nascent form in the common choanoflagellate–metazoan ancestor, and was subsequently specialized and elaborated on in each lineage.
Given the limited transcription factor diversity in M. brevicollis, it is notable that the genome encodes representatives of the otherwise metazoan-specific p53, Mycand Sox/TCF transcription factor families. These transcription factors may have had early and critical roles in the evolution of metazoan ancestors by regulating the differential expression of genes to allow multiple cell types to exist in a single organism, and their study in choanoflagellates is a promising future direction.
The M. brevicollis sequence opens the door to genome-enabled studies of choanoflagellates, a diverse group of microbial eukaryotes that are important in their own right as bacterial predators in both marine and freshwater ecosystems. Although M. brevicollis is strictly unicellular, other choanoflagellates facultatively form colonies, and the modulation of these associations by cell signalling, adhesion, transcriptional regulation and environmental influences is poorly understood. An integrative approach that unites studies of choanoflagellate genomes, cell biology and ecology with the biogeochemistry of the Precambrian promises to reveal the intrinsic and extrinsic factors underlying metazoan origins.