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von der Dunk, S. H. A.

Publications and source records attributed to von der Dunk, S. H. A..

3 recordsLinked to original sources

Intracellular signaling in proto-eukaryotes evolves to alleviate regulatory conflicts of endosymbiosis

The complex eukaryotic cell resulted from a merger between simpler prokaryotic cells, yet the relative timing and the role of the mitochondrial endosymbiosis with respect to other eukaryotic innovations has remained under dispute. Although expansion of the regulatory repertoire has been inferred from phylogenetic studies, gene regulation has not been taken into account in current scenarios of the mitochondrial endosymbiosis which mostly focus on the complementary energetic and ecological perspectives. The endosymbiotic state introduced several unique challenges to cells such as coordination of host and symbiont cell cycles and its disruption by leaking gene products and DNA fragments between host and symbionts. To investigate how these unique challenges 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. The most commonly evolved mechanism, implicit control, works without signaling between host and symbiont. Signaling only evolves under the influence of leaking gene products, while such regulatory interference is inherently harmful. In the fittest evolutionary replicate, the host controls the symbiont cell cycle entirely through signaling, mimicking the regulatory dominance of the nucleus over the mitochondrion that evolved during eukaryogenesis.

evolutionary biology↗

Integrating phylogenetics with intron positions illuminates the origin of the complex spliceosome

Eukaryotic genes are characterised by the presence of introns that are removed from the pre-mRNA by the 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 work has established that these introns and the spliceosomal core originated from self-splicing introns in prokaryotes. Yet it remains largely elusive how the spliceosomal core expanded by recruiting many additional proteins. In this study we use phylogenetic analyses to infer the evolutionary history of the 145 proteins that we could trace back to the spliceosome in the last eukaryotic common ancestor (LECA). We found that an overabundance of proteins derived from ribosome-related processes were 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.

evolutionary biology↗

Evolution of Regulatory Complexity for Cell-Cycle Control

How complexity arises is a fundamental evolutionary question. Complex gene regulation is thought to arise by the interplay between adaptive and non-adaptive forces at multiple organizational levels. Using a computational model, we investigate how complexity arises in cell-cycle regulation. Starting from the well-known Caulobacter crescentus network, we study how cells adapt their cell-cycle behaviour to a gradient of limited nutrient conditions using 10 replicate in silico evolution experiments. We find adaptive expansion of the gene regulatory network: improvement of cell-cycle behaviour allows cells to overcome the inherent cost of complexity. 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. The generalist and specialist strategies are contingent on the regulatory mechanisms that arise early in evolution, but they are not directly linked to network expansion and overall fitness. This study shows that functionality of cells depends on the combination of gene regulatory network topology and genome structure. 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. Complex gene regulation can arise adaptively both from expansion of the regulatory network and from the genomic organization of the elements in this network, demonstrating that to understand complex gene regulation and its evolution, it is necessary to integrate systems that are often studied separately.

evolutionary biology↗