Dr Sam Von Der Dunk

Abstract:

The complex eukaryotic cell resulted from a merger between simpler prokaryotic cells, yet the role of the mitochondrial endosymbiosis with respect to other eukaryotic innovations has remained under dispute. To investigate how the regulatory challenges associated with the endosymbiotic state impacted genome and network evolution during eukaryogenesis, we study a constructive computational model where two simple cells are forced into an obligate endosymbiosis. Across multiple in silico evolutionary replicates, we observe the emergence of different mechanisms for the coordination of host and symbiont cell cycles, stabilizing the endosymbiotic relationship. In most cases, coordination is implicit, without signaling between host and symbiont. Signaling only evolves when there is leakage of regulatory products between host and symbiont. In the fittest evolutionary replicate, the host has taken full control of the symbiont cell cycle through signaling, mimicking the regulatory dominance of the nucleus over the mitochondrion that evolved during eukaryogenesis.

Abstract:

The endosymbiosis of an alpha-proteobacterium that gave rise to mitochondria was one of the key events in eukaryogenesis. One striking outcome of eukaryogenesis was a much more complex cell with a large genome. Despite the existence of many alternative hypotheses for this and other patterns potentially related to endosymbiosis, a constructive evolutionary model in which these hypotheses can be studied is still lacking. Here, we present a theoretical approach in which we focus on the consequences rather than the causes of mitochondrial endosymbiosis. Using a constructive evolutionary model of cell-cycle regulation, we find that genome expansion and genome size asymmetry arise from emergent host-symbiont cell-cycle coordination. We also find that holobionts with large host and small symbiont genomes perform best on long timescales and mimic the outcome of eukaryogenesis. By designing and studying a constructive evolutionary model of obligate endosymbiosis, we uncovered some of the forces that may drive the patterns observed in nature. Our results provide a theoretical foundation for patterns related to mitochondrial endosymbiosis, such as genome size asymmetry, and reveal evolutionary outcomes that have not been considered so far, such as cell-cycle coordination without direct communication.

Abstract:

Eukaryotic genes are characterized by the presence of introns that are removed from pre-mRNA by a spliceosome. This ribonucleoprotein complex is comprised of multiple RNA molecules and over a hundred proteins, which makes it one of the most complex molecular machines that originated during the prokaryote-to-eukaryote transition. Previous works have established that these introns and the spliceosomal core originated from self-splicing introns in prokaryotes. Yet, how the spliceosomal core expanded by recruiting many additional proteins remains largely elusive. In this study, we use phylogenetic analyses to infer the evolutionary history of 145 proteins that we could trace back to the spliceosome in the last eukaryotic common ancestor. We found that an overabundance of proteins derived from ribosome-related processes was added to the prokaryote-derived core. Extensive duplications of these proteins substantially increased the complexity of the emerging spliceosome. By comparing the intron positions between spliceosomal paralogs, we infer that most spliceosomal complexity postdates the spread of introns through the proto-eukaryotic genome. The reconstruction of early spliceosomal evolution provides insight into the driving forces behind the emergence of complexes with many proteins during eukaryogenesis.

Abstract:

Many questions remain about the interplay between adaptive and neutral processes leading to genome expansion and the evolution of cellular complexity. Genome size appears to be tightly linked to the size of the regulatory repertoire of cells (van Nimwegen E. 2003. Scaling laws in the functional content of genomes. Trends Gen. 19(9):479-484). In the context of gene regulation, we here study the interplay between adaptive and nonadaptive forces on genome and regulatory network in a computational model of cell-cycle adaptation to different environments. Starting from the well-known Caulobacter crescentus network, we report on ten replicate in silico evolution experiments where cells evolve cell-cycle control by adapting to increasingly harsh spatial habitats. We find adaptive expansion of the regulatory repertoire of cells. Having a large genome is inherently costly, but also allows for improved cell-cycle behavior. Replicates traverse different evolutionary trajectories leading to distinct eco-evolutionary strategies. In four replicates, cells evolve a generalist strategy to cope with a variety of nutrient levels; in two replicates, different specialist cells evolve for specific nutrient levels; in the remaining four replicates, an intermediate strategy evolves. These diverse evolutionary outcomes reveal the role of contingency in a system under strong selective forces. This study shows that functionality of cells depends on the combination of regulatory network topology and genome organization. For example, the positions of dosage-sensitive genes are exploited to signal to the regulatory network when replication is completed, forming a de novo evolved cell cycle checkpoint. Our results underline the importance of the integration of multiple organizational levels to understand complex gene regulation and the evolution thereof.