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Evolution of multicellularity and somatic cell specialization

Periodic Reporting for period 1 - EVOSOM (Evolution of multicellularity and somatic cell specialization)

Reporting period: 2017-05-01 to 2018-10-31

The evolution of multicellular organisms was a major event in the history of life, because it allowed cells to specialize into functions other than mere propagation. The specialized cells became organized into tissues and organs and thus greatly expanded the ability of the organism to perform a broad range of complex behaviours. In modern multicellular organisms the specialized cells that form the body (soma) of the organism vastly outnumber the germ cells that are responsible for its propagation.

While yielding immense gain of function, the organisation of the somatic cells into tissues and organs required novel intercellular communication systems to control the growth and differentiation of the specialized cell types at the correct time and place and in correct proportions within the organism.

We seek to identify the genetic changes that caused the transitions from uni- to multicellularity and that enabled cell-type specialization. Because modern organisms like ourselves are too complex to investigate this problem, we use the Dictyostelid social amoebas that maximally specialize into five cell types for this research.

Social amoebas aggregate together and form multicellular fruiting bodies when starved. They evolved from unicellular Amoebozoa and are subdivided into 4 major groups. Species in groups 1, 2 and 3 have at most 2 cell types, but 3 new cell types (basal disc, upper- and lower cup) appeared in group 4. Because species in all four groups have about 12000 genes, actually less than found in many unicellular amoebas, we know that neither the transition from uni- to multicellularity nor the appearance of novel cell types requires more genes.

We have a few clues what might be required: Firstly, we noted when comparing gene expression patterns between group 4 and groups 1,2 and 3, the patterns in group 4 were more complex, due to genes acquiring more regulatory sequences. Secondly, gene function also mattered, with cell-communication genes being particularly important for regulating multicellularity and cell specialization. Among about 500 genes known to be essential for Dictyostelium multicellular development, the genes encoding proteins inside the cell that process extracellular signals are also present in unicellular amoebas, and are mostly the same between the 4 groups of Dictyostelia. However, the genes that encode signal peptides or enzymes that synthesize signals, and the receptor proteins on the cell surface that detect signals are mostly different between unicellular and multicellular amoebas and between Dictyostelium groups.

Starting from the hypothesis that diversification of signals and receptors and diversification of gene regulation mechanisms are major drivers of multicellular evolution, we designed a series of experiments to investigate whether this is the case or whether other processes are also or more important. Overall the project has the following objectives
1. Understand the genetic changes that caused transitions to multicellularity.
2. Retrace the evolutionary history and genetic changes that caused somatic cell specialization.
Resolving these objectives will present a major breakthrough in our understanding of the evolution of multicellular life forms.

Significance for society
Why are we here and where do we come from are humanity’s earliest and most profound questions. While most of the world’s religions provide individual mythologies about the origins of life and the universe, the only unifying explanation can come from science. By elucidating the molecular changes that caused a major evolutionary transition, we contribute to the great scientific endeavour to understand the world around us and to separate fact from fiction in retracing the history of life.

In more practical terms the project will highlight many novel genes and cell communication pathways important for regulating life cycle changes and cell differentiation in Amoebozoa, the sister group to Opisthokonta that
1. To understand the order in which novel cell types evolved it is essential to have a well-resolved family tree of the Dictyostelia and their closest Amoebozoan relatives. We constructed such a family tree by amplifying and sequencing the six conserved genes over 34 Dictyostelium species and combining this information with genes from 18 sequenced genomes, half of which were sequenced by us. By comparing the extent to which the conserved genes started to differ from each other by accumulating mutations over time, we derived a family tree for the Dictyostelia. The novel tree subdivides the Dictyostelia in two major branches, each containing two major groups, and with the positions of all smaller groups well resolved. This tree allows us to reconstruct the timeline at which novel cell-types appeared (Schilde et al., in press).

2. Cell differentiate by triggering RNA transcription from different groups of genes. The RNA transcripts then become translated into a range of novel proteins, which alter the appearance and function of the cells. To retrace the evolutionary progression of cell differentiation, we purified cell types from Dictyostelium species taken from each of the 4 major groups and sequenced their transcriptomes (all RNAs expressed in a particular species). In the initial analysis of the transcriptome of the model organisms D. discoideum, we found cup cells, a novel cell type in group 4 are derived from stalk cells. However, while stalk cells mostly express genes related to stalk wall synthesis, cup cells expressed novel genes related to signal processing and cell adhesion. (Kin et al. BMC Genomics 19:764, 2018).

3. Glycogen synthase kinase 3 (GSK3) regulates many cell fate decisions in human development. In multicellular structures of the group 4 species Dictyostelium discoideum, GSK3 promotes spore over basal disc differentiation. We investigated the role of GSK3 in the group 2 species Polysphondylium pallidum, which does not form a basal disc. However, unlike group 4, group 2 species can still encyst individually when starved. We found that deletion of the GSK3 gene had no effect on spore differentiation, but caused cells to choose encystation in preference to multicellular fruiting body formation. This indicated that the original role of GSK3 was to promote multicellularity over unicellular encystation. (Kawabe et al. EvoDevo 9:12. 2018).