Insight
is our reward

Publications in Biology by NOMIS researchers

NOMIS Researcher(s)

Published in

January 30, 2025

Human accelerated regions (HARs) have been implicated in human brain evolution. However, insight into the genes and pathways they control is lacking, hindering the understanding of their function. Here, we identify 2,963 conserved gene targets for 1,590 HARs and their orthologs in human and chimpanzee neural stem cells (NSCs). Conserved gene targets are enriched for neurodevelopmental functions and are overrepresented among differentially expressed genes (DEGs) identified in human NSCs (hNSCs) and chimpanzee NSCs (cNSCs) as well as in human versus non-human primate brains. Species-specific gene targets do not converge on any function and are not enriched among DEGs. HAR targets also show cell-type-specific expression in the human fetal brain, including in outer radial glia, which are linked to cortical expansion. Our findings support that HARs influence brain evolution by altering the expression of ancestral gene targets shared between human and chimpanzee rather than by gaining new targets in human and facilitate hypothesis-directed studies of HAR biology.

Research field(s)
Bioinformatics, Developmental Biology, Evolutionary Biology

NOMIS Researcher(s)

Published in

January 9, 2025

The impacts of degradation and deforestation on tropical forests are poorly understood, particularly at landscape scales. We present an extensive ecosystem analysis of the impacts of logging and conversion of tropical forest to oil palm from a large-scale study in Borneo, synthesizing responses from 82 variables categorized into four ecological levels spanning a broad suite of ecosystem properties: (i) structure and environment, (ii) species traits, (iii) biodiversity, and (iv) ecosystem functions. Responses were highly heterogeneous and often complex and nonlinear. Variables that were directly impacted by the physical process of timber extraction, such as soil structure, were sensitive to even moderate amounts of logging, whereas measures of biodiversity and ecosystem functioning were generally resilient to logging but more affected by conversion to oil palm plantation.

Research field(s)
Conservation Biology, Forestry, Ecology, Environmental Sciences

NOMIS Researcher(s)

Published in

January 2, 2025

Glacier-fed streams (GFS) feature among Earth’s most extreme aquatic ecosystems marked by pronounced oligotrophy and environmental fluctuations. Microorganisms mainly organize in biofilms within them, but how they cope with such conditions is unknown. Here, leveraging 156 metagenomes from the Vanishing Glaciers project obtained from sediment samples in GFS from 9 mountains ranges, we report thousands of metagenome-assembled genomes (MAGs) encompassing prokaryotes, algae, fungi and viruses, that shed light on biotic interactions within glacier-fed stream biofilms. A total of 2,855 bacterial MAGs were characterized by diverse strategies to exploit inorganic and organic energy sources, in part via functional redundancy and mixotrophy. We show that biofilms probably become more complex and switch from chemoautotrophy to heterotrophy as algal biomass increases in GFS owing to glacier shrinkage. Our MAG compendium sheds light on the success of microbial life in GFS and provides a resource for future research on a microbiome potentially impacted by climate change.

Research field(s)
Biology, Evolutionary Biology

NOMIS Researcher(s)

Published in

January 1, 2025

The rapid melting of mountain glaciers and the vanishing of their streams is emblematic of climate change1,2. Glacier-fed streams (GFSs) are cold, oligotrophic and unstable ecosystems in which life is dominated by microbial biofilms2,3. However, current knowledge on the GFS microbiome is scarce4,5, precluding an understanding of its response to glacier shrinkage. Here, by leveraging metabarcoding and metagenomics, we provide a comprehensive survey of bacteria in the benthic microbiome across 152 GFSs draining the Earth’s major mountain ranges. We find that the GFS bacterial microbiome is taxonomically and functionally distinct from other cryospheric microbiomes. GFS bacteria are diverse, with more than half being specific to a given mountain range, some unique to single GFSs and a few cosmopolitan and abundant. We show how geographic isolation and environmental selection shape their biogeography, which is characterized by distinct compositional patterns between mountain ranges and hemispheres. Phylogenetic analyses furthermore uncovered microdiverse clades resulting from environmental selection, probably promoting functional resilience and contributing to GFS bacterial biodiversity and biogeography. Climate-induced glacier shrinkage puts this unique microbiome at risk. Our study provides a global reference for future climate-change microbiology studies on the vanishing GFS ecosystem.

Research field(s)
Biology, Evolutionary Biology

INTRODUCTION: While there may be microbial contributions to Alzheimer’s disease (AD), findings have been inconclusive. We recently reported an AD-associated CD83(+)microglia subtype associated with increased immunoglobulinG4(IgG4) in the transverse colon (TC).

METHODS: We used immunohistochemistry (IHC), IgG4 repertoire profiling, and brain organoid experiments to explore this association.

RESULTS: CD83(+) microglia in the superior frontal gyrus (SFG) are associated with elevated IgG4 and human cytomegalovirus (HCMV) in the TC, anti-HCMV IgG4 in cerebrospinal fluid, and both HCMV and IgG4 in the SFG and vagal nerve. This association was replicated in an independent AD cohort. HCMV-infected cerebral organoids showed accelerated AD pathophysiological features (Aβ42 and pTau-212) and neuronal death.

DISCUSSION: Findings indicate complex, cross-tissue interactions between HCMV and the adaptive immune response associated with CD83(+)microglia in persons with AD. This may indicate an opportunity for antiviral therapy in persons with AD and biomarker evidence of HCMV, IgG4, or CD83(+)microglia.

Research field(s)
Genetics & Heredity, Neurology & Neurosurgery, Biology

NOMIS Researcher(s)

October 1, 2024

Animal speciation often involves novel behavioral features that rely on nervous system evolution. Human-specific brain features have been proposed to underlie specialized cognitive functions and to be linked, at least in part, to the evolution of synapses, neurons, and circuits of the cerebral cortex. Here, we review recent results showing that, while the human cortex is composed of a repertoire of cells that appears to be largely similar to the one found in other mammals, human cortical neurons do display specialized features at many levels, from gene expression to intrinsic physiological properties. The molecular mechanisms underlying human species-specific neuronal features remain largely unknown but implicate hominid-specific gene duplicates that encode novel molecular modifiers of neuronal function. The identification of human-specific genetic modifiers of neuronal function brings novel insights on brain evolution and function and, could also provide new insights on human species-specific vulnerabilities to brain disorders.

Research field(s)
Genetics & Heredity, Evolutionary Biology

NOMIS Researcher(s)

September 19, 2024

Runoff from rapidly melting mountain glaciers is a dominant source of riverine organic carbon in many high-latitude and high-elevation regions. Glacier dissolved organic carbon is highly bioavailable, and its composition likely reflects internal (e.g., autotrophic production) and external (i.e., atmospheric deposition) sources. However, the balance of these sources across Earth’s glaciers is poorly understood, despite implications for the mineralization and assimilation of glacier organic carbon within recipient ecosystems. We assessed the molecular-level composition of dissolved organic matter from 136 mountain glacier outflows from 11 regions covering six continents using ultrahigh resolution 21 T mass spectrometry. We found substantial diversity in organic matter composition with coherent and predictable (80% accuracy) regional patterns. Employing stable and radiocarbon isotopic analyses, we demonstrate that these patterns are inherently linked to atmospheric deposition and in situ production. In remote regions like Greenland and New Zealand, the glacier organic matter pool appears to be dominated by in situ production. However, downwind of industrial centers (e.g., Alaska and Nepal), fossil fuel combustion byproducts likely underpin organic matter composition, resulting in older and more aromatic material being exported downstream. These findings highlight that the glacier carbon cycle is spatially distinct, with ramifications for predicting the dynamics and fate of glacier organic carbon concurrent with continued retreat and anthropogenic perturbation.

Research field(s)
Conservation Biology, Biology

NOMIS Researcher(s)

Published in

August 13, 2024

The nuclear basket attaches to the nucleoplasmic side of the nuclear pore complex (NPC), coupling transcription to mRNA quality control and export. The basket expands the functional repertoire of a subset of NPCs in Saccharomyces cerevisiae by drawing a unique RNA/protein interactome. Yet, how the basket docks onto the NPC core remains unknown. By integrating AlphaFold-based interaction screens, electron microscopy and membrane-templated reconstitution, we uncovered a membrane-anchored tripartite junction between basket and NPC core. The basket subunit Nup60 harbours three adjacent short linear motifs, which connect Mlp1, a parallel homodimer consisting of coiled-coil segments interrupted by flexible hinges, and the Nup85 subunit of the Y-complex. We reconstituted the Y-complex•Nup60•Mlp1 assembly on a synthetic membrane and validated the protein interfaces in vivo. Here we explain how a short linear motif-based protein junction can substantially reshape NPC structure and function, advancing our understanding of compositional and conformational NPC heterogeneity.

Research field(s)
Biochemistry & Molecular Biology, Biology

NOMIS Researcher(s)

Published in

July 17, 2024

Logged and disturbed forests are often viewed as degraded and depauperate environments compared with primary forest. However, they are dynamic ecosystems1 that provide refugia for large amounts of biodiversity2,3, so we cannot afford to underestimate their conservation value4. Here we present empirically defined thresholds for categorizing the conservation value of logged forests, using one of the most comprehensive assessments of taxon responses to habitat degradation in any tropical forest environment. We analysed the impact of logging intensity on the individual occurrence patterns of 1,681 taxa belonging to 86 taxonomic orders and 126 functional groups in Sabah, Malaysia. Our results demonstrate the existence of two conservation-relevant thresholds. First, lightly logged forests (<29% biomass removal) retain high conservation value and a largely intact functional composition, and are therefore likely to recover their pre-logging values if allowed to undergo natural regeneration. Second, the most extreme impacts occur in heavily degraded forests with more than two-thirds (>68%) of their biomass removed, and these are likely to require more expensive measures to recover their biodiversity value. Overall, our data confirm that primary forests are irreplaceable5, but they also reinforce the message that logged forests retain considerable conservation value that should not be overlooked.

Research field(s)
Conservation Biology, Forestry, Ecology, Environmental Sciences

NOMIS Researcher(s)

Published in

July 10, 2024

The emergence of single nucleus RNA sequencing (snRNA-seq) offers to revolutionize the study of Alzheimer’s disease (AD). Integration with complementary multiomics data such as genetics, proteomics and clinical data provides powerful opportunities to link cell subpopulations and molecular networks with a broader disease-relevant context. We report snRNA-seq profiles from superior frontal gyrus samples from 101 well characterized subjects from the Banner Brain and Body Donation Program in combination with whole genome sequences. We report findings that link common AD risk variants with CR1 expression in oligodendrocytes as well as alterations in hematological parameters. We observed an AD-associated CD83(+) microglial subtype with unique molecular networks and which is associated with immunoglobulin IgG4 production in the transverse colon. Our major observations were replicated in two additional, independent snRNA-seq data sets. These findings illustrate the power of multi-tissue molecular profiling to contextualize snRNA-seq brain transcriptomics and reveal disease biology.

Research field(s)
Genetics & Heredity, Biology

NOMIS Researcher(s)

Published in

June 20, 2024

Gamete formation and subsequent offspring development often involve extended phases of suspended cellular development or even dormancy. How cells adapt to recover and resume growth remains poorly understood. Here, we visualized budding yeast cells undergoing meiosis by cryo-electron tomography (cryoET) and discovered elaborate filamentous assemblies decorating the nucleus, cytoplasm, and mitochondria. To determine filament composition, we developed a “filament identification” (FilamentID) workflow that combines multiscale cryoET/cryo-electron microscopy (cryoEM) analyses of partially lysed cells or organelles. FilamentID identified the mitochondrial filaments as being composed of the conserved aldehyde dehydrogenase Ald4ALDH2 and the nucleoplasmic/cytoplasmic filaments as consisting of acetyl-coenzyme A (CoA) synthetase Acs1ACSS2. Structural characterization further revealed the mechanism underlying polymerization and enabled us to genetically perturb filament formation. Acs1 polymerization facilitates the recovery of chronologically aged spores and, more generally, the cell cycle re-entry of starved cells. FilamentID is broadly applicable to characterize filaments of unknown identity in diverse cellular contexts.

Research field(s)
Microbiology, Biology

NOMIS Researcher(s)

Published in

June 20, 2024

Sexually reproducing eukaryotes employ a developmentally regulated cell division program—meiosis—to generate haploid gametes from diploid germ cells. To understand how gametes arise, we generated a proteomic census encompassing the entire meiotic program of budding yeast. We found that concerted waves of protein expression and phosphorylation modify nearly all cellular pathways to support meiotic entry, meiotic progression, and gamete morphogenesis. Leveraging this comprehensive resource, we pinpointed dynamic changes in mitochondrial components and showed that phosphorylation of the FoF1-ATP synthase complex is required for efficient gametogenesis. Furthermore, using cryoET as an orthogonal approach to visualize mitochondria, we uncovered highly ordered filament arrays of Ald4ALDH2, a conserved aldehyde dehydrogenase that is highly expressed and phosphorylated during meiosis. Notably, phosphorylation-resistant mutants failed to accumulate filaments, suggesting that phosphorylation regulates context-specific Ald4ALDH2 polymerization. Overall, this proteomic census constitutes a broad resource to guide the exploration of the unique sequence of events underpinning gametogenesis.

Research field(s)
Biology

A key feature of many developmental systems is their ability to self-organize spatial patterns of functionally distinct cell fates. To ensure proper biological function, such patterns must be established reproducibly, by controlling and even harnessing intrinsic and extrinsic fluctuations. While the relevant molecular processes are increasingly well understood, we lack a principled framework to quantify the performance of such stochastic self-organizing systems. To that end, we introduce an information-theoretic measure for self-organized fate specification during embryonic development. We show that the proposed measure assesses the total information content of fate patterns and decomposes it into interpretable contributions corresponding to the positional and correlational information. By optimizing the proposed measure, our framework provides a normative theory for developmental circuits, which we demonstrate on lateral inhibition, cell type proportioning, and reaction–diffusion models of self-organization. This paves a way toward a classification of developmental systems based on a common information-theoretic language, thereby organizing the zoo of implicated chemical and mechanical signaling processes.

Research field(s)
Biology

NOMIS Researcher(s)

Published in

May 28, 2024

Suspended animation states allow organisms to survive extreme environments. The African turquoise killifish has evolved diapause as a form of suspended development to survive a complete drought. However, the mechanisms underlying the evolution of extreme survival states are unknown. To understand diapause evolution, we performed integrative multi-omics (gene expression, chromatin accessibility, and lipidomics) in the embryos of multiple killifish species. We find that diapause evolved by a recent remodeling of regulatory elements at very ancient gene duplicates (paralogs) present in all vertebrates. CRISPR-Cas9-based perturbations identify the transcription factors REST/NRSF and FOXOs as critical for the diapause gene expression program, including genes involved in lipid metabolism. Indeed, diapause shows a distinct lipid profile, with an increase in triglycerides with very-long-chain fatty acids. Our work suggests a mechanism for the evolution of complex adaptations and offers strategies to promote long-term survival by activating suspended animation programs in other species.

Research field(s)
Molecular Biology, Biochemistry & Molecular Biology, Developmental Biology, Genetics & Heredity

NOMIS Researcher(s)

Published in

May 13, 2024

Retrospective lineage reconstruction of humans predicts that dramatic clonal imbalances in the body can be traced to the 2-cell stage embryo. However, whether and how such clonal asymmetries arise in the embryo is unclear. Here, we performed prospective lineage tracing of human embryos using live imaging, non-invasive cell labeling, and computational predictions to determine the contribution of each 2-cell stage blastomere to the epiblast (body), hypoblast (yolk sac), and trophectoderm (placenta). We show that the majority of epiblast cells originate from only one blastomere of the 2-cell stage embryo. We observe that only one to three cells become internalized at the 8-to-16-cell stage transition. Moreover, these internalized cells are more frequently derived from the first cell to divide at the 2-cell stage. We propose that cell division dynamics and a cell internalization bottleneck in the early embryo establish asymmetry in the clonal composition of the future human body.

Research field(s)
Biology

NOMIS Researcher(s)

Published in

April 4, 2024

Genomic DNA that resides in the nuclei of mammalian neurons can be as old as the organism itself. The life span of nuclear RNAs, which are critical for proper chromatin architecture and transcription regulation, has not been determined in adult tissues. In this work, we identified and characterized nuclear RNAs that do not turn over for at least 2 years in a subset of postnatally born cells in the mouse brain. These long-lived RNAs were stably retained in nuclei in a neural cell type–specific manner and were required for the maintenance of heterochromatin. Thus, the life span of neural cells may depend on both the molecular longevity of DNA for the storage of genetic information and also the extreme stability of RNA for the functional organization of chromatin.

Research field(s)
Genetics & Heredity, Biology

NOMIS Researcher(s)

Published in

March 14, 2024

Genome-wide association studies (GWAS) identified thousands of genetic variants linked to phenotypic traits and disease risk. However, mechanistic understanding of how GWAS variants influence complex morphological traits and can, in certain cases, simultaneously confer normal-range phenotypic variation and disease predisposition, is still largely lacking. Here, we focus on rs6740960, a single nucleotide polymorphism (SNP) at the 2p21 locus, which in GWAS studies has been associated both with normal-range variation in jaw shape and with an increased risk of non-syndromic orofacial clefting. Using in vitro derived embryonic cell types relevant for human facial morphogenesis, we show that this SNP resides in an enhancer that regulates chondrocytic expression of PKDCC – a gene encoding a tyrosine kinase involved in chondrogenesis and skeletal development. In agreement, we demonstrate that the rs6740960 SNP is sufficient to confer chondrocyte-specific differences in PKDCC expression. By deploying dense landmark morphometric analysis of skull elements in mice, we show that changes in Pkdcc dosage are associated with quantitative changes in the maxilla, mandible, and palatine bone shape that are concordant with the facial phenotypes and disease predisposition seen in humans. We further demonstrate that the frequency of the rs6740960 variant strongly deviated among different human populations, and that the activity of its cognate enhancer diverged in hominids. Our study provides a mechanistic explanation of how a common SNP can mediate normal-range and disease-associated morphological variation, with implications for the evolution of human facial features.

Research field(s)
Developmental Biology, Genetics & Heredity, Evolutionary Biology

NOMIS Researcher(s)

Published in

March 1, 2024

Most cryospheric ecosystems are energy limited. How their energetics will respond to climate change remains largely unknown. This is particularly true for glacier-fed streams, which interface with the cryosphere and initiate some of Earth’s largest river systems. Here, by studying resource stoichiometry and microbial energetics in 154 glacier-fed streams sampled by the Vanishing Glaciers project across Earth’s major mountain ranges, we show that these ecosystems and their benthic microbiome are overall carbon and phosphorus limited. Threshold elemental ratios and low carbon use efficiencies (median: 0.15) modelled from extracellular enzymatic activities corroborate resource limitation in agreement with maintenance metabolism of benthic microorganisms. Space-for-time substitution analyses suggest that glacier shrinkage will stimulate benthic primary production in glacier-fed streams, thereby relieving microbial metabolism from carbon limitation. Concomitantly, we find that increasing streamwater temperature will probably stimulate microbial growth (temperature sensitivity: 0.62 eV). Consequently, elevated microbial demands for phosphorus, but diminishing inputs from subglacial sources, may intensify phosphorus limitation as glaciers shrink. Our study thus unveils a ‘green transition’ towards autotrophy in the world’s glacier-fed streams, entailing shifts in the energetics of their microorganisms.

Research field(s)
Ecology, Environmental Sciences

NOMIS Researcher(s)

November 16, 2023

Biological conservation practices and approaches take many forms. Conservation projects do not only differ in their aims and methods, but also concerning their conceptual and normative background assumptions and their underlying motivations and objectives. We draw on philosophical distinctions from the ethics of conservation to explain variances of different positions on conservation projects along six dimensions: (1) conservation ideals, (2) intervention intuitions, (3) the moral considerability of nonhuman beings, (4) environmental values, (5) views on nature and (6) human roles in nature. The result is a map of the moral landscape of biological conservation, on which these six dimensions are layered. This map functions as a heuristic tool to understand conceptual and normative foundations of specific conservation projects, which we will illustrate with four paradigmatic examples: the Pisavaara Strict Nature Reserve, Predator Free New Zealand, the Oostvaardersplassen Nature Reserve and the Great Green Wall Project. With this map as a heuristic tool, we aim to conceptually illuminate disagreement and clarify misunderstandings between representatives of different environmental protection strategies and to show that the same project can be supported (or criticised) on different grounds.

Research field(s)
Biology, Environmental Sciences

NOMIS Researcher(s)

Published in

October 14, 2023

Remote sensing of vegetation by spectroscopy is increasingly used to characterize trait distributions in plant communities. How leaves interact with electromagnetic radiation is determined by their structure and contents of pigments, water, and abundant dry matter constituents like lignins, phenolics, and proteins. High-resolution (“hyperspectral”) spectroscopy can characterize trait variation at finer scales, and may help to reveal underlying genetic variation—information important for assessing the potential of populations to adapt to global change. Here, we use a set of 360 inbred genotypes of the wild coyote tobacco Nicotiana attenuata: wild accessions, recombinant inbred lines (RILs), and transgenic lines (TLs) with targeted changes to gene expression, to dissect genetic versus non-genetic influences on variation in leaf spectra across three experiments. We calculated leaf reflectance from hand-held field spectroradiometer measurements covering visible to short-wave infrared wavelengths of electromagnetic radiation (400–2500 nm) using a standard radiation source and backgrounds, resulting in a small and quantifiable measurement uncertainty. Plants were grown in more controlled (glasshouse) or more natural (field) environments, and leaves were measured both on- and off-plant with the measurement set-up thus also in more to less controlled environmental conditions. Entire spectra varied across genotypes and environments. We found that the greatest variance in leaf reflectance was explained by between-experiment and non-genetic between-sample differences, with subtler and more specific variation distinguishing groups of genotypes. The visible spectral region was most variable, distinguishing experimental settings as well as groups of genotypes within experiments, whereas parts of the short-wave infrared may vary more specifically with genotype. Overall, more genetically variable plant populations also showed more varied leaf spectra. We highlight key considerations for the application of field spectroscopy to assess genetic variation in plant populations. © 2023, BioMed Central Ltd., part of Springer Nature.

Research field(s)
Natural Sciences, Biology, Plant Biology & Botany

NOMIS Researcher(s)

May 16, 2023

Aim: Globally distributed plant trait data are increasingly used to understand relationships between biodiversity and ecosystem processes. However, global trait databases are sparse because they are compiled from many, mostly small databases. This sparsity in both trait space completeness and geographical distribution limits the potential for both multivariate and global analyses. Thus, ‘gap-filling’ approaches are often used to impute missing trait data. Recent methods, like Bayesian hierarchical probabilistic matrix factorization (BHPMF), can impute large and sparse data sets using side information. We investigate whether BHPMF imputation leads to biases in trait space and identify aspects influencing bias to provide guidance for its usage. Innovation: We use a fully observed trait data set from which entries are randomly removed, along with extensive but sparse additional data. We use BHPMF for imputation and evaluate bias by: (1) accuracy (residuals, RMSE, trait means), (2) correlations (bi- and multivariate) and (3) taxonomic and functional clustering (valuewise, uni- and multivariate). BHPMF preserves general patterns of trait distributions but induces taxonomic clustering. Data set–external trait data had little effect on induced taxonomic clustering and stabilized trait–trait correlations. Main Conclusions: Our study extends the criteria for the evaluation of gap-filling beyond RMSE, providing insight into statistical data structure and allowing better informed use of imputed trait data, with improved practice for imputation. We expect our findings to be valuable beyond applications in plant ecology, for any study using hierarchical side information for imputation. © 2023 The Authors. Global Ecology and Biogeography published by John Wiley & Sons Ltd.

Research field(s)
Natural Sciences, Biology, Ecology