Evolution of multicellularity and somatic cell specialization

Informations projet

EVOSOM

N° de convention de subvention: 742288

DOI

10.3030/742288

Projet clôturé

Date de signature de la CE 26 Avril 2017

Date de début 1 Mai 2017

Date de fin 30 Avril 2023

Financé au titre de

• EXCELLENT SCIENCE - European Research Council (ERC)

Coût total

€ 2 128 602,00

Contribution de l’UE

€ 2 128 602,00

Coordonné par

UNIVERSITY OF DUNDEE
United Kingdom

Periodic Reporting for period 4 - EVOSOM (Evolution of multicellularity and somatic cell specialization)

Période du rapport: 2021-11-01 au 2023-04-30

Résumé du contexte et des objectifs généraux du projet

The evolution of multicellular organisms was a major event in the history of life, because it allowed cells to specialize into functions other than propagation. The specialized cells became organized into tissues and organs and greatly expanded the ability of the organism to perform complex behaviours. In modern organisms the specialized cells that form the body (soma) vastly outnumber the germ cells that cause its propagation. While providing greater functionality, the organisation of the somatic cells into tissues and organs required novel communication systems to control the growth, differentiation and correct positioning of the specialized cells.
We seek to identify the genetic changes that caused transitions from uni- to multicellularity and that enabled cell-type specialization. Because modern organisms like us are too complex to investigate this problem, we use the Dictyostelid social amoebas that maximally specialize into five cell types.
When starved, social amoebas aggregate together and form multicellular fruiting bodies with resilient spores. They evolved from unicellular Amoebozoa which form cysts when starved and are subdivided into 4 major groups. Species in groups 1, 2 and 3 have at most 2 cell types, spores and stalk cells but 2 new cell types (disc and cup) emerged 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 required more genes.

We have a few clues what might be required: Firstly, we noted when comparing gene expression patterns between group 4 and groups 1-3, the patterns in group 4 were more complex, due to genes acquiring more regulatory sequences. Secondly, gene function mattered. The genes encoding intracellular proteins that process extracellular signals are present throughout Dictyostelias and also in unicellular amoebas. 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 groups and between unicellular and multicellular amoebas.

Starting from the hypothesis that diversification of signals and receptors and diversification of gene regulation mechanisms are drivers of multicellular evolution, we designed experiments to investigate whether this is the case or whether other processes 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.
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, 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 also contains the animal lineage. Many of these genes are likely to be conserved in the animal lineage and lead to novel discoveries important for understanding human health and disease.

Travail effectué depuis le début du projet jusqu’à la fin de la période considérée dans le rapport et principaux résultats atteints jusqu’à présent

1. Identify cell-type specific protein subsets: Cells differentiate by triggering RNA transcription from specific subsets of genes. The RNA transcripts are translated into proteins, which alter the structure and function of the cells. To identify these subsets and understand how they evolved, we purified cell types from species taken from each of the 4 major groups and sequenced their RNAs. Broadly, the spores, stalk and disc cells expressed different subsets of proteins involved cell wall synthesis, while the cup cells expressed novel protein with roles in communication, motility and adhesion. (Kin BMC Genomics, 2018).
2. Evolutionary genetic change: Regulatory genes that process perceived signals into cell differentiation make up several families such as receptors to detect the signals, protein kinases and GTPases to transduce it and transcription factors that regulate gene expression. We used available genome and transcriptome data to record conservation and change in protein functional domains, cell-type specificity and developmental regulation of these genes across Dictyostelid evolution (Forbes GBE 2019; Forbes SmallGTPases 2022; Hall Open ResEur 2023; Kin CellSignal 2023). This work yielded many clues for changes that might have caused cell-type innovations.
3. A novel cell type by gene duplication: We noticed a group 4 specific gene duplication in the transcription factor cdl1. Gene knock-out of 1 copy cdl1A showed that this gene was essential for the evolution of cup cells. Cdl1 initial function was in stalk formation (Kin CurrBiol 2022).
4. Novel gene functions: Many genes, such as gskA, dgcA, stlB, acaA, acrA, acgA, atg7 that are essential for group 4 development were deleted in P. pallidum (Ppal) and P.violaceum (Pvio) which reside in group 2 and just outside to group 4, respectively. Loss of dgcA, acaA, acrA, acgA produced less severe effects in Ppal and Pvio than in group 4, loss of stlB had the opposite effect. Loss of gskA, which in group 4 promotes spore over disc differentiation has no role in Ppal spore formation, but causes cells to aggregate when starved rather than encyst individually (Kawabe EvoDevo 2018; Narita GenomeBiolEvol 2020; Kawabe EvoDevo 2022). The essential role of the autophagy gene atg7 in spore gene expression was conserved (Du OpenResEur 2022).
5. Ultimate cause: To understand if and why spores formed multicellularly are better than individually formed cysts, we recorded their long-term survival under climate mimicking conditions It appeared that spores were frost resistant while cysts were not, due to greater state of compaction and thicker more structured wall of the spores. Dictyostelia evolved from unicellular amoebas just after the neoproterozoid glaciations (snowball earth) and group 4 with the most frost resistant spores still uniquely colonizes arctic regions. Dictyostelid multicellular sporulation was therefore likely caused by a cooling climate (Lawal, SciRep 2020).
6. Autophagy of soma feeds the spores. We found early spore gene expression requires autophagy (self-digestion) and that unlike cysts, spores formed from single cells are not viable.
Because autophagy mostly occurs in stalk cells, which self-digest before dying, spores likely build up their thicker walls and food stores from nutrients produced by stalk autophagy.

Progrès au-delà de l’état des connaissances et impact potentiel prévu (y compris l’impact socio-économique et les conséquences sociétales plus larges du projet jusqu’à présent)

1. Identification of gene duplication as the molecular cause for novel cell type evolution. While such a mechanism was proposed, we provided the first evidence that it actually occurs
2. Identification of climate change as the ultimate cause for multicellular sporulation
3. The realization that stalk cells do not just lift the spores but feed them through autophagy puts a new perspective on the evolution of multicellularity.

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