Publikationen

The transition from an autotrophic to a heterotrophic lifestyle is associated with numerous genomic changes. These often involve large genomic alterations, potentially driven by repetitive DNAs. Despite their recognized role in shaping plant genomes, the contribution of repetitive DNAs to parasitic plant genome evolution remains largely unexplored. This study presents the first analysis of repetitive DNAs in Hydnoraceae genomes, a plant family whose members are holoparasitic. Repetitive DNAs were identified and annotated de novo. Abundant transposable elements and 35S ribosomal DNA in the Hydnora visseri genome were reconstructed in silico. Their patterns of abundance and presence-absence were individually and comparatively analyzed. Both Hydnoraceae genera, Hydnora and Prosopanche, exhibit distinct repeatome profiles which challenge our current understanding of repeatome and rDNA evolution. The Hydnora genomes are dominated by long terminal repeat retrotransposons, while the Prosopanche genomes vary greatly in their repeat composition: Prosopanche bonacinae with a highly abundant single DNA transposon and Prosopanche panguanensis with over 15% 5S rDNA, compared to ≤ 0.1% in the Hydnora genomes. The repeat profiles align with the phylogeny, geographical distribution, and host shifts of the Hydnoraceae, indicating a potential role of repetitive DNAs in shaping Hydnoraceae genomes to adapt to the parasitic lifestyle.

Macromolecular assembly between biomolecules dictates the material state of chemically complex aqueous dispersions such as the cytoplasm. The formation of protein precipitates, fibers, or liquid droplets have been associated with metabolic regulation and disease. However, the effect of metabolic flux on the material properties of aqueous dispersions remains underexplored. Here, we use the protometabolic reduction of NAD+ to NADH by pyruvate to study the effect of NADH production on the phase separation properties of polyarginine. We show that reduction of NAD+ in the presence of polyarginine can tune the material properties of the dispersion between precipitates, homogeneous solution, and liquid droplets depending on the buffer concentration. In situ droplet formation results in 2-3 times higher reaction rate and NADH yield, compared to homogeneous solution. Our study provides a setting for coupling protometabolism to active protocell environments in the absence of enzymes and sheds light on the self-regulation of metabolic flux on mediating biomolecular phase separation.

Does an ecological community allow stable species coexistence? Identifying the general effects of competitive, mutualistic, and predator-prey interactions on stability remains a central problem of systems ecology because established approaches cannot account for the full network arrangement of these interactions. Here, we therefore analyze all interaction networks of N≤5 species with Lotka-Volterra dynamics by combining exact results and numerical exploration. We find that a very small subset of these networks is "impossible ecologies," in which stable coexistence is non-trivially impossible. We prove that the possibility of stable coexistence is determined by similarly rare "irreducible ecologies." Statistical sampling shows that this probability varies over orders of magnitude even in ecologies that differ only in the network arrangement of identical interactions. Thus, our approach reveals that the full network structure of interactions can influence stability of coexistence more than the established effect of interaction-type proportions. A record of this paper's transparent peer review process is included in the supplemental information.

The marine annelid Platynereis dumerilii is a model organism used in many research areas including evolution and development, neurobiology, ecology and regeneration. Here we present the genomes of P. dumerilii (laboratory culture reference and a single individual assembly) and of the closely related P. massiliensis and P. megalops (single individual assembly) to facilitate comparative genomic approaches and help explore Platynereis biology. We used long-read sequencing technology and chromosomal-conformation capture along with extensive transcriptomic resources to obtain and annotate a draft genome assembly of ~ 1.47 Gbp for P. dumerilii, of which more than half represent repeat elements. We predict around 29,000 protein-coding genes, with relatively large intron sizes, over 38,000 non-coding genes, and 105 miRNA loci. We further explore the high genetic variation (~ 3% heterozygosity) within the Platynereis species complex. Gene ontology reveals the most variable loci to be associated with pigmentation, development and immunity. The current work sets the stage for further development of Platynereis genomic resources.

Folding of the neocortex is a fundamental feature of brain development in many mammalian species, notably in most non-human primates and in particular in human. Cortical folding is thought to allow fitting a larger cortical surface area, with a greater number of neurons, into the limited size of the cranial cavity. Here, we review the following key topics related to cortical folding. We first discuss principles of cortical folding and dissect the factors contributing to the mechanical asymmetry that is thought to have a key role in folding. We then address the evolution of cortical folding and discuss the two principal types of folding, the conserved folding and the evolved folding, and the roles of neuron production vs. neuron migration in these two types. We then sequentially review human models, animal models and computational models of cortical folding. This includes a discussion of human malformations of cortical folding, the potential of cerebral organoids to study folding, the power of the ferret model to dissect mechanisms of cortical folding, and the use of computational models to make predictions about cortical folding. Finally, we address future perspectives of folding research and outline directions that research may take.

Many internal organs in the body harbor a fluid-filled lumen. Lumen nucleation and fusion have been reported as dependent on organ-type during organogenesis. In contrast, the physics of lumen suggests that force balance between luminal pressure and cell mechanics leads to generic rules. However, this hypothesis lacks experimental evidence. Here we compare lumen dynamics for three different systems (MDCK cysts, pancreatic spheres, and epiblast model) by using quantitative cell biology, microfabrication, and theory. We report that the initial cell number determines the maximum number of lumens but does not impact the steady state, which is a final single lumen. We show that lumen dynamics is determined by luminal hydrostatic pressure. We also use MDCK cysts to manipulate cell adhesion and lumen volume to successfully reproduce the fusion dynamics of pancreatic spheres and epiblasts. Our results reveal self-organisation rules of lumens with relevance for morphogenesis and tissue engineering.

Whereas alignment has been fundamental to sequence-based assessments of protein homology, it is ineffective for intrinsically disordered regions (IDRs) due to their lowered sequence conservation and unique sequence properties. Here, we present a web server implementation of SHARK (bio-shark.org), an alignment-free algorithm for homology classification that compares the overall amino acid composition and short regions (k-mers) shared between sequences (SHARK-scores). The output of such k-mer-based comparisons is used by SHARK-dive, a machine learning classifier to detect homology between unalignable, disordered sequences. SHARK-web provides sequence-versus-database assessment of protein sequence homology akin to conventional tools such as BLAST and HMMER. Additionally, we provide precomputed sets of IDR sequences from 16 model organism proteomes facilitating searches against species-specific IDR-omes. SHARK-dive offers superior overall homology detection performance to BLAST and HMMER, driven by a large increase in sensitivity to low sequence identity homologs, and can be used to facilitate the study of sequence-function relationships in disordered, difficult-to-align regions.

The formation of complex tissues during embryonic development requires an intricate spatiotemporal coordination of local mechanical processes regulating global tissue morphogenesis. Here, we uncover a novel mechanism that mechanically regulates the shape of the anterior neural plate (ANP), a vital forebrain precursor, during zebrafish gastrulation. Combining in vivo and in silico approaches we reveal that the ANP is shaped by global tissue flows regulated by distinct force-generating processes. We show that mesendoderm migration and E-cadherin-dependent differential tissue interactions control distinct flow regimes in the neuroectoderm. Initial opposing flows lead to neuroectoderm cell internalisation and progressive multilayer tissue folding which in turn provide forces driving ANP tissue reshaping. We find that convergent extension is dispensable for internalisation but required for ANP tissue extension. Our results highlight how spatiotemporal regulation and coupling of different mechanical processes between tissues in the embryo control the first internalisation and folding events of the developing brain.

Upregulation of insulin mRNA translation upon hyperglycemia in pancreatic islet β-cells involves several RNA-binding proteins. Here, we found that G3BP1, a stress granule marker downregulated in islets of subjects with type 2 diabetes, binds to insulin mRNA in glucose concentration-dependent manner. We show in mouse insulinoma MIN6-K8 cells exposed to fasting glucose levels that G3BP1 and its paralog G3BP2 colocalize to cytosolic condensates with eIF3b, phospho-AMPKαThr172 and Ins1/2 mRNA. Glucose stimulation dissolves G3BP1+/2+ condensates with cytosolic redistribution of their components. The aldolase inhibitor aldometanib prevents the glucose- and pyruvate-induced dissolution of G3BP1+/2+ condensates, increases phospho-AMPKαThr172 levels and reduces those of phospho-mTORSer2448. G3BP1 or G3BP2 depletion precludes condensate assembly. KO of G3BP1 decreases Ins1/2 mRNA abundance and translation as well as proinsulin levels, and impaires glucose-stimulated insulin secretion. Further, other insulin secretagogues such as exendin-4 and palmitate, but not high KCl, prompts the dissolution of G3BP1+/2+ condensates. G3BP1+/2+/Ins mRNA+ condensates are also found in primary mouse and human β-cells. Hence, G3BP1+/2+ condensates represent a conserved glycolysis/aldolase-regulated compartment for the physiological storage and protection of insulin mRNA in resting β-cells.

Aptamers, nucleic acid ligands targeting specific molecules, have emerged as drug candidates, sensors, imaging tools and nanotechnology building blocks. The predominant method for their discovery, systematic evolution of ligands by exponential enrichment, while successful, is laborious, time-consuming and often results in candidates enriched for unintended criteria. Here we present UltraSelex, a noniterative method that combines biochemical partitioning, high-throughput sequencing and computational signal-to-background rank modeling for discovering RNA aptamers in about 1 day. UltraSelex identified high-affinity RNA aptamers capable of binding a fluorogenic silicon rhodamine dye and two protein targets, the SARS-CoV-2 RNA-dependent RNA polymerase and HIV reverse transcriptase, enabling live-cell RNA imaging and efficient enzyme inhibition, respectively. From the ranked sequences, minimal aptamer motifs could be easily inferred. UltraSelex provides a rapid route to reveal new drug candidates and diagnostic tools.