One for all, all for one, or – what does it take to be multicellular?
When people think of biology, ‘big’ often comes to mind: elephants, whales, redwoods. A closer look, though, reveals that the vast majority of organisms are in fact unicellular: think bacteria, archaea, and countless algae and fungi. But what does it take for a cell to make the leap to become part of something greater than itself, a multicellular organism? Things get interesting when we examine organisms living on the cusp between uni- and multicellularity.
Meet Dictyostelium, a genus of eukaryotes containing species that can exist as both single-celled amoebae and multicellular aggregates. The life history of D. discoideum, the best-studied species of this genus, illustrates the challenges of living in multicellular structures. ‘Dicty’ cells can live a fully unicellular life, preying on bacteria and happily multiplying. But normally solo-operating Dicties sometimes find themselves in nutrient-poor environments, at which point they let loose a call for help in the form of a small molecule, cyclic adenosine monophosphate (cAMP). Nearby Dicty cells, sensing this desperate cry – “cAMP! cAAAAAMP!” – will migrate towards the signalling epicentre and form a large multicellular aggregate, charmingly called a slug. This slug migrates to a new location, where certain lucky cells form reproductive spores inside a ‘fruiting body,’ which is supported by a sterile stalk composed of considerably unluckier cells. The spores are released into the environment with the hope of reaching a more nutrient-rich location. But how do these cells decide amongst themselves which ones will get another shot at survival and reproduction in the form of spore dissemination? Since the cells are not genetically identical, their evolutionary interests clash – and the fittest ones, containing the most advantageous genetic variants, are likelier to produce spores (1).
For some time, the cells work as a single cooperative, albeit ‘sluggish’ unit: they move with coordination and purpose, tightly adhering to each other. However, competition between these genetically distinct cells arises pretty quickly, which poses a problem to becoming a bona fide multicellular organism – we’ll come back to how such competition can be avoided. For now, we can turn to more concrete forms of multi-celled life to shed more light on what it takes to truly be multicellular…
A relevant group of organisms are the members of a lineage of green algae, the Volvocaceae. In this lineage, multicellularity is a recent development in evolutionary terms, with different species exhibiting different ‘stages’ of it. Chlamydomonas species represent the ancestral, unicellular form of the lineage, while individuals of the Pandorina species have 16 cells, and those of the genus Volvox have thousands. Therefore, the mechanisms by which multicellularity arose in this lineage can be traced by comparing its various members. Compared to their single-celled cousins, Volvox during their evolution repurposed genes to perform functions necessary to multicellular life. Additionally, they possess expanded ‘gene families’ that arose from single genes, with each ‘family member’ now carrying out a different function related to the organisation of their multicellular bodies (2). Thus single-celled organisms often already possess certain tools useful to multicellular life. With relatively minor changes to their genomes, they are able to evolve into more complex forms.
Animal genomes have been compared to those of their closest relatives that exhibit facultative (optional) multicellularity, including, but not limited to, the previously mentioned slime moulds, such as Dicty, and green algae, such as Volvocaceae. These studies suggest that key players in the early stages of acquisition of multicellularity were genes involved in cytokinesis (the physical separation of cells during cell division) and genes encoding components of the extracellular matrix (ECM – a collection of proteins found in the space between cells that provides structural and functional cohesion in multicellular organisms). Therefore, in animals and in plants, it is almost certain that clonal cells (daughter cells produced by successive cell divisions of a single, original cell) banded together through incomplete cytokinesis to form the first proto-animals and proto-plants respectively (3). This overcomes the ‘competition’ element that we observe in the case of aggregation of heterogeneous cells, such as in the case of Dicty. The single-cell ‘bottleneck’ imposed on each successive generation of animals and plants in the form of the zygote ensures streamlined genetics and evolutionary goals, reducing competition between cells of a single organism.
Acquisition of multicellularity often and rapidly leads to division of labour between different, cooperating cell types. Organisms no longer need to temporally vary their phenotype to meet the demands of a changing environment, as they allocate different functions to their different cell types. For instance, the most famous of the Volvox species, V. carteri, has two cell types: somatic and reproductive. With evolutionary time, organisms often develop greater numbers of increasingly specialised cell types, which are in turn much more dependent on each other. Division of labour therefore makes it difficult for organisms to revert to an ancestral unicellular ‘multitasker’ form, instead leading to increasingly complex multicellular lifeforms with interdependent cells (3).
It has recently been argued, though, that it isn’t only changes in cells that drive the evolution of multicellularity. It has been suggested (4) that the aforementioned ECM itself is not in fact simply a result of multicellular evolution, but that its presence actively promotes it. The ECM acts as a dynamic control structure, allowing the organisation of extracellular space and coordinating the intercellular processes of increasingly complex organisms. This challenges the cell-centric dogma of the evolution of multicellularity, as it isn’t just cells, but also their immediate surroundings, that must undergo changes to become compatible with a multicellular lifestyle. Characteristically, ECM occupies the majority of the volume of V. carteri – what would this species be without its ECM?
Genetic uniformity, adaptation of the (extra)cellular environment, cooperation and functional specialisation may begin to explain what it takes for a cell to be able to form part of an organism greater than itself. No matter how well these principles are understood though (and there is still a long way to go), the intricate structures that relatively simple single cells can build when they form part of multicellular lifeforms will never stop being magnificent.
References
- Castillo D, Queller D, Strassmann J. Cell condition, competition, and chimerism in the social amoeba Dictyostelium discoideum. Ethology Ecology & Evolution. 2011;23(3):262-273.
- Herron M. Origins of multicellular complexity: Volvox and the volvocine algae. Molecular Ecology. 2016;25(6):1213-1223.
- Brunet T, King N. The Origin of Animal Multicellularity and Cell Differentiation. Developmental Cell. 2017;43(2):124-140.
- Bich L, Pradeu T, Moreau J. Understanding Multicellularity: The Functional Organization of the Intercellular Space. Frontiers in Physiology. 2019;10.
About the Author: Alexandra Bisia studied Development, Regeneration and Stem Cells at the University of Edinburgh. She is currently in her second year of doctoral studies at the University of Oxford in the Chromosome and Developmental Biology Wellcome Trust programme. She is carrying out her research in Prof Liz Robertson’s lab on mouse trophoblast stem cells.
Comments from our judge, Dr Jennifer Rohn (@JennyRohn) on the winner of the 2020 competition: This year’s winning entry is a tour de force of writing — nuanced, humorous and highly original.
