TY - JOUR A1 - Cheng, Feng A1 - Dennis, Alice B. A1 - Osuoha, Josephine Ijeoma A1 - Canitz, Julia A1 - Kirschbaum, Frank A1 - Tiedemann, Ralph T1 - A new genome assembly of an African weakly electric fish (Campylomormyrus compressirostris, Mormyridae) indicates rapid gene family evolution in Osteoglossomorpha JF - BMC genomics N2 - Background Teleost fishes comprise more than half of the vertebrate species. Within teleosts, most phylogenies consider the split between Osteoglossomorpha and Euteleosteomorpha/Otomorpha as basal, preceded only by the derivation of the most primitive group of teleosts, the Elopomorpha. While Osteoglossomorpha are generally species poor, the taxon contains the African weakly electric fish (Mormyroidei), which have radiated into numerous species. Within the mormyrids, the genus Campylomormyrus is mostly endemic to the Congo Basin. Campylomormyrus serves as a model to understand mechanisms of adaptive radiation and ecological speciation, especially with regard to its highly diverse species-specific electric organ discharges (EOD). Currently, there are few well-annotated genomes available for electric fish in general and mormyrids in particular. Our study aims at producing a high-quality genome assembly and to use this to examine genome evolution in relation to other teleosts. This will facilitate further understanding of the evolution of the osteoglossomorpha fish in general and of electric fish in particular. Results A high-quality weakly electric fish (C. compressirostris) genome was produced from a single individual with a genome size of 862 Mb, consisting of 1,497 contigs with an N50 of 1,399 kb and a GC-content of 43.69%. Gene predictions identified 34,492 protein-coding genes, which is a higher number than in the two other available Osteoglossomorpha genomes of Paramormyrops kingsleyae and Scleropages formosus. A Computational Analysis of gene Family Evolution (CAFE5) comparing 33 teleost fish genomes suggests an overall faster gene family turnover rate in Osteoglossomorpha than in Otomorpha and Euteleosteomorpha. Moreover, the ratios of expanded/contracted gene family numbers in Osteoglossomorpha are significantly higher than in the other two taxa, except for species that had undergone an additional genome duplication (Cyprinus carpio and Oncorhynchus mykiss). As potassium channel proteins are hypothesized to play a key role in EOD diversity among species, we put a special focus on them, and manually curated 16 Kv1 genes. We identified a tandem duplication in the KCNA7a gene in the genome of C. compressirostris. Conclusions We present the fourth genome of an electric fish and the third well-annotated genome for Osteoglossomorpha, enabling us to compare gene family evolution among major teleost lineages. Osteoglossomorpha appear to exhibit rapid gene family evolution, with more gene family expansions than contractions. The curated Kv1 gene family showed seven gene clusters, which is more than in other analyzed fish genomes outside Osteoglossomorpha. The KCNA7a, encoding for a potassium channel central for EOD production and modulation, is tandemly duplicated which may related to the diverse EOD observed among Campylomormyrus species. KW - Campylomormyrus KW - Pacbio sequencing KW - Gene family KW - Osteoglossomorpha KW - Kv1 Y1 - 2023 U6 - https://doi.org/10.1186/s12864-023-09196-6 SN - 1471-2164 VL - 24 IS - 1 PB - BMC CY - London ER - TY - JOUR A1 - Córdoba, Sandra Correa A1 - Tong, Hao A1 - Burgos, Asdrubal A1 - Zhu, Feng A1 - Alseekh, Saleh A1 - Fernie, Alisdair R. A1 - Nikoloski, Zoran T1 - Identification of gene function based on models capturing natural variability of Arabidopsis thaliana lipid metabolism JF - Nature Communications N2 - The use of automated tools to reconstruct lipid metabolic pathways is not warranted in plants. Here, the authors construct Plant Lipid Module for Arabidopsis rosette using constraint-based modeling, demonstrate its integration in other plant metabolic models, and use it to dissect the genetic architecture of lipid metabolism. Lipids play fundamental roles in regulating agronomically important traits. Advances in plant lipid metabolism have until recently largely been based on reductionist approaches, although modulation of its components can have system-wide effects. However, existing models of plant lipid metabolism provide lumped representations, hindering detailed study of component modulation. Here, we present the Plant Lipid Module (PLM) which provides a mechanistic description of lipid metabolism in the Arabidopsis thaliana rosette. We demonstrate that the PLM can be readily integrated in models of A. thaliana Col-0 metabolism, yielding accurate predictions (83%) of single lethal knock-outs and 75% concordance between measured transcript and predicted flux changes under extended darkness. Genome-wide associations with fluxes obtained by integrating the PLM in diel condition- and accession-specific models identify up to 65 candidate genes modulating A. thaliana lipid metabolism. Using mutant lines, we validate up to 40% of the candidates, paving the way for identification of metabolic gene function based on models capturing natural variability in metabolism. KW - Biochemical networks KW - Biochemical reaction networks KW - Genetic models KW - Plant molecular biology Y1 - 2023 U6 - https://doi.org/10.1038/s41467-023-40644-9 SN - 2041-1723 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Tomowski, Maxi A1 - Lozada-Gobilard, Sissi Donna A1 - Jeltsch, Florian A1 - Tiedemann, Ralph T1 - Recruitment and migration patterns reveal a key role for seed banks in the meta-population dynamics of an aquatic plant JF - Scientific reports N2 - Progressive habitat fragmentation threatens plant species with narrow habitat requirements. While local environmental conditions define population growth rates and recruitment success at the patch level, dispersal is critical for population viability at the landscape scale. Identifying the dynamics of plant meta-populations is often confounded by the uncertainty about soil-stored population compartments. We combined a landscape-scale assessment of an amphibious plant's population structure with measurements of dispersal complexity in time to track dispersal and putative shifts in functional connectivity. Using 13 microsatellite markers, we analyzed the genetic structure of extant Oenanthe aquatica populations and their soil seed banks in a kettle hole system to uncover hidden connectivity among populations in time and space. Considerable spatial genetic structure and isolation-by-distance suggest limited gene flow between sites. Spatial isolation and patch size showed minor effects on genetic diversity. Genetic similarity found among extant populations and their seed banks suggests increased local recruitment, despite some evidence of migration and recent colonization. Results indicate stepping-stone dispersal across adjacent populations. Among permanent and ephemeral demes the resulting meta-population demography could be determined by source-sink dynamics. Overall, these spatiotemporal connectivity patterns support mainland-island dynamics in our system, highlighting the importance of persistent seed banks as enduring sources of genetic diversity. Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-37974-5 SN - 2045-2322 VL - 13 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Arend, Marius A1 - Zimmer, David A1 - Xu, Rudan A1 - Sommer, Frederik A1 - Mühlhaus, Timo A1 - Nikoloski, Zoran T1 - Proteomics and constraint-based modelling reveal enzyme kinetic properties of Chlamydomonas reinhardtii on a genome scale JF - Nature Communications N2 - Metabolic engineering of microalgae offers a promising solution for sustainable biofuel production, and rational design of engineering strategies can be improved by employing metabolic models that integrate enzyme turnover numbers. However, the coverage of turnover numbers for Chlamydomonas reinhardtii, a model eukaryotic microalga accessible to metabolic engineering, is 17-fold smaller compared to the heterotrophic cell factory Saccharomyces cerevisiae. Here we generate quantitative protein abundance data of Chlamydomonas covering 2337 to 3708 proteins in various growth conditions to estimate in vivo maximum apparent turnover numbers. Using constrained-based modeling we provide proxies for in vivo turnover numbers of 568 reactions, representing a 10-fold increase over the in vitro data for Chlamydomonas. Integration of the in vivo estimates instead of in vitro values in a metabolic model of Chlamydomonas improved the accuracy of enzyme usage predictions. Our results help in extending the knowledge on uncharacterized enzymes and improve biotechnological applications of Chlamydomonas. KW - Computational models KW - Enzymes KW - Proteomics Y1 - 2023 U6 - https://doi.org/10.1038/s41467-023-40498-1 SN - 2041-1723 VL - 14 IS - 1 PB - Springer Nature CY - London ER - TY - JOUR A1 - Zavorka, Libor A1 - Blanco, Andreu A1 - Chaguaceda, Fernando A1 - Cucherousset, Julien A1 - Killen, Shaun S. A1 - Lienart, Camilla A1 - Mathieu-Resuge, Margaux A1 - Nemec, Pavel A1 - Pilecky, Matthias A1 - Scharnweber, Inga Kristin A1 - Twining, Cornelia W. A1 - Kainz, Martin J. T1 - The role of vital dietary biomolecules in eco-evo-devo dynamics JF - Trends in ecology and evolution N2 - The physiological dependence of animals on dietary intake of vitamins, amino acids, and fatty acids is ubiquitous. Sharp differences in the availability of these vital dietary biomolecules among different resources mean that consumers must adopt a range of strategies to meet their physiological needs. We review the emerging work on omega-3 long-chain polyunsaturated fatty acids, focusing predominantly on predator-prey interactions, to illustrate that trade-off between capacities to consume resources rich in vital biomolecules and internal synthesis capacity drives differences in phenotype and fitness of consumers. This can then feedback to impact ecosystem functioning. We outline how focus on vital dietary biomolecules in eco-eco-devo dynamics can improve our understanding of anthropogenic changes across multiple levels of biological organization. Y1 - 2023 U6 - https://doi.org/10.1016/j.tree.2022.08.010 SN - 0169-5347 SN - 1872-8383 VL - 38 IS - 1 SP - 72 EP - 84 PB - Cell Press CY - Cambridge ER - TY - JOUR A1 - Grdseloff, Nastasja A1 - Boulday, Gwenola A1 - Roedel, Claudia J. A1 - Otten, Cecile A1 - Vannier, Daphne Raphaelle A1 - Cardoso, Cecile A1 - Faurobert, Eva A1 - Dogra, Deepika A1 - Tournier-Lasserve, Elisabeth A1 - Abdelilah-Seyfried, Salim T1 - Impaired retinoic acid signaling in cerebral cavernous malformations JF - Scientific reports N2 - The capillary-venous pathology cerebral cavernous malformation (CCM) is caused by loss of CCM1/Krev interaction trapped protein 1 (KRIT1), CCM2/MGC4607, or CCM3/PDCD10 in some endothelial cells. Mutations of CCM genes within the brain vasculature can lead to recurrent cerebral hemorrhages. Pharmacological treatment options are urgently needed when lesions are located in deeply-seated and in-operable regions of the central nervous system. Previous pharmacological suppression screens in disease models of CCM led to the discovery that treatment with retinoic acid improved CCM phenotypes. This finding raised a need to investigate the involvement of retinoic acid in CCM and test whether it has a curative effect in preclinical mouse models. Here, we show that components of the retinoic acid synthesis and degradation pathway are transcriptionally misregulated across disease models of CCM. We complemented this analysis by pharmacologically modifying retinoic acid levels in zebrafish and human endothelial cell models of CCM, and in acute and chronic mouse models of CCM. Our pharmacological intervention studies in CCM2-depleted human umbilical vein endothelial cells (HUVECs) and krit1 mutant zebrafish showed positive effects when retinoic acid levels were increased. However, therapeutic approaches to prevent the development of vascular lesions in adult chronic murine models of CCM were drug regiment-sensitive, possibly due to adverse developmental effects of this hormone. A treatment with high doses of retinoic acid even worsened CCM lesions in an adult chronic murine model of CCM. This study provides evidence that retinoic acid signaling is impaired in the CCM pathophysiology and suggests that modification of retinoic acid levels can alleviate CCM phenotypes. KW - Developmental biology KW - Molecular medicine Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-31905-0 SN - 2045-2322 VL - 13 IS - 1 PB - Nature Portfolio CY - Berlin ER - TY - JOUR A1 - Stübler, Sabine A1 - Kloft, Charlotte A1 - Huisinga, Wilhelm T1 - Cell-level systems biology model to study inflammatory bowel diseases and their treatment options JF - CPT: pharmacometrics & systems pharmacology N2 - To help understand the complex and therapeutically challenging inflammatory bowel diseases (IBDs), we developed a systems biology model of the intestinal immune system that is able to describe main aspects of IBD and different treatment modalities thereof. The model, including key cell types and processes of the mucosal immune response, compiles a large amount of isolated experimental findings from literature into a larger context and allows for simulations of different inflammation scenarios based on the underlying data and assumptions. In the context of a large and diverse virtual IBD population, we characterized the patients based on their phenotype (in contrast to healthy individuals, they developed persistent inflammation after a trigger event) rather than on a priori assumptions on parameter differences to a healthy individual. This allowed to reproduce the enormous diversity of predispositions known to lead to IBD. Analyzing different treatment effects, the model provides insight into characteristics of individual drug therapy. We illustrate for anti-TNF-alpha therapy, how the model can be used (i) to decide for alternative treatments with best prospects in the case of nonresponse, and (ii) to identify promising combination therapies with other available treatment options. Y1 - 2023 U6 - https://doi.org/10.1002/psp4.12932 SN - 2163-8306 VL - 12 IS - 5 SP - 690 EP - 705 PB - Nature Publ. Group CY - London ER - TY - JOUR A1 - Nendel, Claas A1 - Reckling, Moritz A1 - Debaeke, Philippe A1 - Schulz, Susanne A1 - Berg-Mohnicke, Michael A1 - Constantin, Julie A1 - Fronzek, Stefan A1 - Hoffmann, Munir A1 - Jakšić, Snežana A1 - Kersebaum, Kurt-Christian A1 - Klimek-Kopyra, Agnieszka A1 - Raynal, Hélène A1 - Schoving, Céline A1 - Stella, Tommaso A1 - Battisti, Rafael T1 - Future area expansion outweighs increasing drought risk for soybean in Europe JF - Global change biology N2 - The European Union is highly dependent on soybean imports from overseas to meet its protein demands. Individual Member States have been quick to declare self-sufficiency targets for plant-based proteins, but detailed strategies are still lacking. Rising global temperatures have painted an image of a bright future for soybean production in Europe, but emerging climatic risks such as drought have so far not been included in any of those outlooks. Here, we present simulations of future soybean production and the most prominent risk factors across Europe using an ensemble of climate and soybean growth models. Projections suggest a substantial increase in potential soybean production area and productivity in Central Europe, while southern European production would become increasingly dependent on supplementary irrigation. Average productivity would rise by 8.3% (RCP 4.5) to 8.7% (RCP 8.5) as a result of improved growing conditions (plant physiology benefiting from rising temperature and CO2 levels) and farmers adapting to them by using cultivars with longer phenological cycles. Suitable production area would rise by 31.4% (RCP 4.5) to 37.7% (RCP 8.5) by the mid-century, contributing considerably more than productivity increase to the production potential for closing the protein gap in Europe. While wet conditions at harvest and incidental cold spells are the current key challenges for extending soybean production, the models and climate data analysis anticipate that drought and heat will become the dominant limitations in the future. Breeding for heat-tolerant and water-efficient genotypes is needed to further improve soybean adaptation to changing climatic conditions. KW - genotypes KW - legumes KW - maturity groups KW - protein crops KW - protein transition KW - resilience Y1 - 2022 U6 - https://doi.org/10.1111/gcb.16562 SN - 1354-1013 SN - 1365-2486 VL - 29 IS - 5 SP - 1340 EP - 1358 PB - Wiley-Blackwell CY - Ocford [u.a] ER - TY - JOUR A1 - Küken, Anika A1 - Treves, Haim A1 - Nikoloski, Zoran T1 - A simulation-free constrained regression approach for flux estimation in isotopically nonstationary metabolic flux analysis with applications in microalgae JF - Frontiers in plant science : FPLS N2 - Introduction Flux phenotypes from different organisms and growth conditions allow better understanding of differential metabolic networks functions. Fluxes of metabolic reactions represent the integrated outcome of transcription, translation, and post-translational modifications, and directly affect growth and fitness. However, fluxes of intracellular metabolic reactions cannot be directly measured, but are estimated via metabolic flux analysis (MFA) that integrates data on isotope labeling patterns of metabolites with metabolic models. While the application of metabolomics technologies in photosynthetic organisms have resulted in unprecedented data from 13CO2-labeling experiments, the bottleneck in flux estimation remains the application of isotopically nonstationary MFA (INST-MFA). INST-MFA entails fitting a (large) system of coupled ordinary differential equations, with metabolite pools and reaction fluxes as parameters. Here, we focus on the Calvin-Benson cycle (CBC) as a key pathway for carbon fixation in photosynthesizing organisms and ask if approaches other than classical INST-MFA can provide reliable estimation of fluxes for reactions comprising this pathway. Methods First, we show that flux estimation with the labeling patterns of all CBC intermediates can be formulated as a single constrained regression problem, avoiding the need for repeated simulation of time-resolved labeling patterns. Results We then compare the flux estimates of the simulation-free constrained regression approach with those obtained from the classical INST-MFA based on labeling patterns of metabolites from the microalgae Chlamydomonas reinhardtii, Chlorella sorokiniana and Chlorella ohadii under different growth conditions. Discussion Our findings indicate that, in data-rich scenarios, simulation-free regression-based approaches provide a suitable alternative for flux estimation from classical INST-MFA since we observe a high qualitative agreement (rs=0.89) to predictions obtained from INCA, a state-of-the-art tool for INST-MFA. KW - metabolic flux analysis KW - INST-MFA KW - regression KW - 13C labeling KW - algae Y1 - 2023 U6 - https://doi.org/10.3389/fpls.2023.1140829 SN - 1664-462X VL - 14 PB - Frontiers Media CY - Lausanne ER - TY - JOUR A1 - Langary, Damoun A1 - Küken, Anika A1 - Nikoloski, Zoran T1 - The effective deficiency of biochemical networks JF - Scientific reports N2 - The deficiency of a (bio)chemical reaction network can be conceptually interpreted as a measure of its ability to support exotic dynamical behavior and/or multistationarity. The classical definition of deficiency relates to the capacity of a network to permit variations of the complex formation rate vector at steady state, irrespective of the network kinetics. However, the deficiency is by definition completely insensitive to the fine details of the directionality of reactions as well as bounds on reaction fluxes. While the classical definition of deficiency can be readily applied in the analysis of unconstrained, weakly reversible networks, it only provides an upper bound in the cases where relevant constraints on reaction fluxes are imposed. Here we propose the concept of effective deficiency, which provides a more accurate assessment of the network’s capacity to permit steady state variations at the complex level for constrained networks of any reversibility patterns. The effective deficiency relies on the concept of nonstoichiometric balanced complexes, which we have already shown to be present in real-world biochemical networks operating under flux constraints. Our results demonstrate that the effective deficiency of real-world biochemical networks is smaller than the classical deficiency, indicating the effects of reaction directionality and flux bounds on the variation of the complex formation rate vector at steady state. Y1 - 2023 U6 - https://doi.org/10.1038/s41598-023-41767-1 SN - 2045-2322 VL - 13 PB - Springer Nature CY - London ER -