Biology subjects

Kuenzel, S.

Publications and source records attributed to Kuenzel, S..

16 recordsLinked to original sources

bioRxiv2026

Preconception e-nicotine impairs airway development and progenitor proliferation across generations in Drosophila Melanogaster

Electronic nicotine delivery devices are increasingly used worldwide, raising concern about the potential effects of nicotine exposure during fetal and early postnatal development. However, evidence regarding the effects of vaping during pregnancy remains limited, and the consequences of exposure before conception are largely unknown. Here, we investigated whether maternal nicotine vaping prior to conception alters airway development using the fruit fly Drosophila melanogaster. Offspring of nicotine-exposed mothers exhibited abnormal airway architecture, epithelial remodelling, and impaired terminal branching. These defects were accompanied by reduced proliferation of airway progenitor cells without increased apoptosis, resulting in decreased hypoxia tolerance, altered activity patterns, and reduced lifespan. Transcriptomic and functional analyses revealed suppression of innate immune signalling mediated by nuclear factor kappa-B (NF-{kappa}B). Notably, knockdown of its regulator Relish reproduced key phenotypes. Developmental abnormalities persisted across generations, with their severity progressively declining. Together, these findings identify maternal preconception nicotine exposure as a previously unrecognized determinant of airway development and provide insight into early origins of chronic airway disease. TeaserPreconception e-nicotine exposure shapes airway development, structural and physiological abnormalities across generations in Drosophila.

Developmental Biology↗

bioRxiv2026

A reassessment of positive growth effects of expressed random sequence clones in E. coli

De novo gene emergence from non-coding sequences is increasingly recognized as an important evolutionary mechanism, yet the functional potential of random sequences remains debated. Previous experiments suggested that expression of random sequence clones in Escherichia coli can enhance growth of the cells bearing them, i.e. they provide a fitness advantage. However, these findings have been questioned, regarding potential confounding effects of the clone mixtures and a possibly negatively acting peptide expressed from the cloning vector. Here we performed controlled competitive growth assays using a defined subset of 64 random sequence clones representing a spectrum of fitness effects. Experiments across multiple conditions, including two different growth cycle durations, induction states, and replicate sets, showed high technical reproducibility and consistent clone-specific growth trajectories for the majority of the clones, but for some also influences of genomic background and experimental conditions. While vector-derived constructs that inhibit the vector-coded peptide expression showed the same fitness improvements relative to the parental vector that were previously shown, several random sequence clones exhibited higher positive selection coefficients under conditions of exponential growth. These effects persisted even when negative clones were excluded, indicating that they are not driven by competition dynamics with negative clones. Our results demonstrate that positive growth effects of random sequence clones cannot be explained by clone mixture and vector artifacts alone. Instead, a subset of random sequences confers genuine fitness advantages comparable to beneficial mutations observed in experimental evolution studies. These findings provide strong experimental support for the capacity of random sequences to generate adaptive functions and underscore their role in de novo gene evolution. Significance statementThis study provides robust experimental evidence that a subset of random DNA sequences can confer genuine fitness advantages in Escherichia coli, independent of previously proposed artifacts such as vector effects or clone competition. Based on controlled competitive assays across multiple conditions, the results show that these adaptive effects are reproducible and comparable to beneficial mutations observed in experimental evolution. These findings strengthen the case that random sequences can serve as a meaningful source of functional innovation, supporting their role in de novo gene evolution.

evolutionary biology↗

bioRxiv2025

Long-Term Intestinal Epithelial Remodeling Induced by Acute Protein-Energy Malnutrition

Protein-energy malnutrition (PEM) is a global health burden with lasting effects that extend well beyond the initial nutrient deficiency. To systematically investigate the long-term effects of a single episode of PEM on the structure and function of the intestinal epithelium and its associated microbiota, we employed a comprehensive multi-omics approach, including (spatial) transcriptomics, DNA methylation analysis, fecal metagenomics, and metabolomics. Our findings show that PEM persistently alters the intestinal epithelium by depleting Paneth cells and suppressing antimicrobial gene expression - changes linked to DNA methylation that persist despite dietary recovery. In germ-free mice, the sustained epithelial phenotype after was absent. We identified the microbial lipid metabolite 9-HODE and epigenetically deregulated PPAR-driven GDF15 expression as key molecular drivers of the persistent PEM-induced Paneth cell dysfunction. Targeting microbial lipid production and its link to the host GDF15 pathway could offer novel therapeutic strategies for long-term consequences of malnutrition and other Paneth cell-associated diseases.

immunology↗

bioRxiv2024

Greater host influence and promiscuity: How an invasive seaweed host has advantages over co-occurring natives

The surface microbiome of seaweed hosts is a multi-domain biofilm regulated by host-microbe and microbe-microbe interactions. The extent to which hosts influence these interactions, and potentially affect their resilience and invasion success, remains unclear. We experimentally tested whether hosts with invasion history exert more influence over their biofilms than native hosts. Biofilm formation on proxy surfaces adjacent to one invasive (Gracilaria vermiculophylla) and two native (Fucus serratus, Fucus vesiculosus) co-occurring hosts was monitored and compared to mature epiphytic biofilms of the same hosts. Only Gracilarias proxy biofilms were significantly different in community composition compared to control surfaces. Gracilarias proxy biofilms also showed the highest similarity to their adjacent algae sharing certain bacterial taxa that were absent in control treatments, indicating that colonization of the proxy surface was influenced by the host. Gracilaria and its proxy biofilm showed highest similarity in microbial network variables, suggesting a higher ability of the invader to influence connectivity and microbial associations within its biofilm. Meanwhile Gracilarias mature biofilm also showed higher variability in its prokaryotic composition over experiments, which was also reflected in a less robust microbial network in both Gracilaria and its proxy biofilms. This suggests that in addition to stronger influence in the invasive host, it was also more promiscuous towards potential symbionts from the environment. Ultimately, through examining microbial interactions, in line with previous research we found that host influence and promiscuity may play an important role in seaweed hosts to acclimate to different environmental condition and successfully thrive in new ecosystems.

molecular biology↗

bioRxiv2024

Seasonal cycles in a seaweed holobiont: A multiyear time series reveals repetitive microbial shifts and core taxa

Seasonality is an important natural feature that drives cyclic environmental changes. Seaweed holobionts, inhabiting shallow waters such as rocky shores and mud flats, are subject to seasonal changes in particular, but little is known on the influence of seasonality on their microbial communities. In this study, we conducted a bi-monthly, three-year time series to assess the seasonality of microbial epibiota in the seaweed holobiont Gracilaria vermiculophylla. Our results reveal pronounced seasonal shifts that are both taxonomic and functional, oscillating between late winter and early summer across consecutive years. While epibiota varied taxonomically between populations, they were functionally similar, indicating that seasonal variability drives functional changes, while spatial variability is more redundant. We also identified seasonal core microbiota that consistently (re)associated with the host at specific times, alongside a permanent core that is present year-round, independent of season or geography. These findings highlight the dynamic yet resilient nature of seaweed holobionts and demonstrate that their epibiota undergo predictable changes. Therewith, the research offers important insights into the temporal dynamics of seaweed-associated microbiota, and demonstrates that the relationship between seaweed host and its epibiota is not static, but naturally subject to an ongoing seasonal succession process.

ecology↗

bioRxiv2024

Patterns of extreme outlier RNA expression in population data reveal sporadic over-activation of genes with co-regulated modules in subsets of individuals

BackgroundMost RNA-Seq datasets harbor genes with extreme expression levels in some samples. Such extreme outliers are usually treated as technical errors and are removed from the data before further statistical analysis. Here we focus on the patterns of such outlier expression. ResultsOur study is based on multiple datasets, including outbred and inbred mice, humans from the GTEx dataset, different Drosophila species and single-nuclei sequencing experiments from human brain tissues. All show comparable general patterns of outlier expression. Different individuals can harbor very different numbers of outliers, with some individuals showing extreme numbers in only one out of several organs of the respective individual. A three-generation family analysis in mice was generated and analyzed for the inheritance of outlier patterns. We find that most extreme over-expressions are not inherited, i.e., appear to be sporadically generated in individuals. Still, co-regulated outlier expressions are identifiable in various gene groups, and some correspond with known pathways. Among the co-regulated genes with extreme outlier expression are also the hormone genes prolactin and growth hormone, both in mice and humans, for which we include also protein level data from human cohorts. ConclusionsWe show that outlier patterns of gene expression are a biological reality occurring universally across tissues and species. Most of the outlier expressions are spontaneous and not inherited. We discuss the possibility that the outlier patterns reflect edge of chaos effects that are expected for systems of non-linear interactions and feedback loops, such as gene regulatory networks.

genomics↗

bioRxiv2024

Between a Warm Winter and a Cold Spell: Physiological Responses to Changing Winter Climate in Amphibians

Climate change is swiftly altering environmental winter conditions, leading to significant ecological impacts such as phenological shifts in many species. As a result, animals might face physiological mismatches due to longer or earlier activity periods and are at risk of being exposed to late spring freezes. Our study points for the first time to the complex physiological challenges that amphibians face as a result of changing thermal conditions due to winter climate change. We investigated the physiological responses to a period of warmer winter days and sudden spring freeze in the common toad (Bufo bufo) by acclimating them to 4{degrees}C or 8{degrees}C for 48 h or exposing them to 4{degrees}C or -2{degrees}C for 6 h, respectively. We assessed the daily energy demands, determined body condition and cold tolerance, explored the molecular responses to freezing through hepatic tissue transcriptome analysis, and measured blood glucose levels. Toads acclimated to higher temperatures showed a higher daily energy expenditure and a reduced cold tolerance suggesting faster depletion of energy stores and the loss of winter acclimation during warmer winters. Blood sugar levels were higher in frozen toads indicating the mobilization of cryoprotective glucose with freezing which was further supported by changed patterns in proteins related to glucose metabolism. Overall, our results emphasize that increased thermal variability incurs physiological costs that may reduce energy reserves and thus affect amphibian health and survival. This might pose a serious threat to breeding adults and may have subsequent effects at the population level.

ecology↗

bioRxiv2023

Gut-associated functions are favored during microbiome assembly across C. elegans life

The microbiome expresses a variety of functions that influence host biology. The range of functions depends on composition of the microbiome, which itself can change during the lifetime of the host as a consequence of neutral assembly processes, host-mediated selection, and/or environmental conditions. To date, the exact dynamics of microbiome assembly, the underlying determinants as well as the resulting effects on host-associated functions are not always well understood. Here, we used the nematode Caenorhabditis elegans and a defined community of fully sequenced, naturally associated bacteria to study microbiome dynamics and functions across the lifetime of individual hosts under controlled experimental conditions. By applying the neutral and null models, we demonstrate that bacterial community composition initially shows strongly declining levels of stochasticity, which, however, increase during late worm life, suggesting the action of random assembly processes in aged hosts following first colonization of C. elegans. The adult microbiome is enriched in strains of the genera Ochrobactrum and Enterobacter in comparison to the direct substrate and a host-free control environment. Using pathway analysis, metabolic, and ecological modelling, we further found that the lifetime assembly dynamics lead to an increase in gut-associated functions in the host-associated microbiome, possibly indicating that the initially colonizing bacteria are beneficial for the worm. Overall, our study introduces a framework for studying microbiome assembly dynamics based on the stochastic models and inference of functions, yielding new insights into the processes determining host-associated microbiome composition and function. ImportanceThe microbiome plays a crucial role in host biology, with its functions depending on microbiome composition that can change during a hosts lifetime. To date, the dynamics of microbiome assembly and the resulting functions are not well understood. This study introduces a new approach to characterize the functional consequences of microbiome assembly by modelling both, the relevance of stochastic processes and metabolic characteristics of microbial community changes. The approach was applied to experimental time series data, obtained for the microbiome of the nematode Caenorhabditis elegans. The results revealed significant differences in host-associated and environmental microbiomes. Stochastic processes only played a minor role, and the host showed an increase in beneficial bacteria and an enrichment of gut-associated functions, possibly indicating that the host actively shapes composition of its microbiome. Overall, this study provides a framework for studying microbiome assembly dynamics and yields new insights into C. elegans microbiome functions.

evolutionary biology↗

bioRxiv2021

Evolution of a new testis-specific functional promotor within the highly conserved Map2k7 gene of the mouse

Map2k7 (synonym Mkk7) is a conserved regulatory kinase gene and a central component of the JNK signaling cascade with key functions during cellular differentiation. It shows complex transcription patterns and different transcript isoforms are known in the mouse (Mus musculus). We have previously identified a newly evolved testis specific transcript for the Map2k7 gene in the subspecies M. m. domesticus. Here, we identify the new promotor that drives this transcript and find that its transcript codes for an open reading frame (ORF) of 50 amino acids. The new promotor was gained in the stem lineage of closely related mouse species, but was secondarily lost in the subspecies M. m. musculus and M. m. castaneus. A single mutation can be correlated with its transcriptional activity in M. m. domesticus and cell culture assays demonstrate the capability of this mutation to drive expression. A mouse knock-out line in which the promotor region of the new transcript is deleted reveals a functional contribution of the newly evolved promotor to sperm motility and to the spermatid transcriptome. Our data show that a new functional transcript (and possibly protein) can evolve within an otherwise highly conserved gene, supporting the notion of regulatory changes contributing to the emergence of evolutionary novelties.

evolutionary biology↗

bioRxiv2021

Molecular diet analysis in zebra and quagga mussels (Dreissena spp.) and an assessment of the utility of aquatic filter feeders as biological eDNA filters

Molecular gut content analysis is a popular tool to study food web interactions and was recently also suggested as an alternative source for DNA based biomonitoring. However, the overabundant consumers DNA often outcompetes that of its diet during PCR. Blocking approaches are an efficient means to reduce consumer amplification while retaining broad specificity for dietary taxa. We here designed an assay to monitor the eukaryotic diet of mussels and test their utility as biological eDNA filters to monitor planktonic communities. We designed several rDNA primer sets with a broad taxonomic suitability for eukaryotes, which suppress the amplification of mussels. The primers were tested using mussel DNA extracts and the results were compared to eDNA water samples collected next to the mussel colonies. Taxonomic recovery, as well as patterns of alpha and beta diversity, were compared between mussels and water samples. In addition, we analyzed time series samples of mussel samples from different German rivers. Our primer sets efficiently block the amplification of various mussel genera. The recovered DNA reflects a broad dietary preference across the eukaryotic tree of life and considerable taxonomic overlap with filtered water samples. We also recover various taxa of possible commensals and parasites, associated with the mussels. Our protocol will enable large scale dietary analysis in mussels, facilitate aquatic food web analysis, elucidate the ecological impact of invasive bivalves and the rapid survey of mussel aquacultures for pathogens. Moreover, we show that mussels could serve as an interesting complementary DNA source for biomonitoring.

ecology↗

bioRxiv2020

Horizontal gene transfer-mediated bacterial strain variation affects host fitness

How microbes affect host fitness and environmental adaptation has become a fundamental research question in evolutionary biology. We tested for associations of bacterial genomic variation and Drosophila melanogaster offspring number in a microbial Genome Wide Association Study (GWAS). Leveraging strain variation in the genus Gluconobacter, a genus of bacteria that are commonly associated with Drosophila under natural conditions, we pinpoint the thiamine biosynthesis pathway (TBP) as contributing to differences in fitness conferred to the fly host. By tracing the evolutionary history of TBP genes in Gluconobacter, we find that TBP genes were most likely lost and reacquired by horizontal gene transfer (HGT). We suggest that HGT might contribute to microbiome flexibility and speculate that it can also more generally contribute to host adaptation.

evolutionary biology↗

bioRxiv2019

Higher stochasticity of microbiota composition in seedlings of domesticated wheat compared to wild wheat

Plants constitute an ecological niche for microbial communities that colonize different plant tissues and explore the plant habitat for reproduction and dispersal. The association of microbiota and plant may be altered by ecological and evolutionary changes in the host population. Seedborne microbiota, expected to be largely vertically-transferred, have the potential to co-adapt with their host over generations. Reduced host diversity because of strong directional selection and polyploidization during plant domestication and cultivation may have impacted the assembly and transmission of seed-associated microbiota. Nonetheless, the effect of plant domestication on the diversity of their associated microbes is poorly understood. Here we show that microbial communities in domesticated wheat, Triticum aestivum, are less diverse but more inconsistent among individual plants compared to the wild wheat species, T. dicoccoides. We found that diversity of microbes in seeds overall is low, but comparable in different wheat species, independent of their genetic and geographic origin. However, the diversity of seedborne microbiota that colonize the roots and leaves of the young seedling is significantly reduced in domesticated wheat genotypes. Moreover, we observe a higher variability between replicates of T. aestivum suggesting a stronger effect of chance events in microbial colonization and assembly. We also propagated wild and domesticated wheat in two different soils and found that different factors govern the assembly of soil-derived and seedborne microbial communities. Overall, our results demonstrate that the role of stochastic processes in seedborne microbial community assembly is larger in domesticated wheat compared to the wild wheat. We suggest that the directional selection on the plant host and polyploidization events during domestication may have decreased the degree of wheat-microbiota interactions and consequently led to a decreased stable core microbiota.

microbiology↗

bioRxiv2019

Microbiota differences of the comb jelly Mnemiopsis leidyi in native and invasive sub-populations

The translocation of non-indigenous species around the world, especially in marine systems, is a matter of concern for biodiversity conservation and ecosystem functioning. While specific traits are often recognized to influence establishment success of non-indigenous species, the impact of the associated microbial community for the fitness, performance and invasion success of basal marine metazoans remains vastly unknown. In this study we compared the microbiota community composition of the invasive ctenophore Mnemiopsis leidyi in different native and invasive sub-populations along with characterization of the genetic structure of the host. By 16S rRNA gene amplicon sequencing we showed that the sister group to all metazoans, namely ctenophores, harbored a distinct microbiota on the animal host, which significantly differed across two major tissues, namely epidermis and gastrodermis. Additionally, we identified significant differences between native and invasive sub-populations of M. leidyi, which indicate, that the microbiota community is likely influenced by the genotypic background of the ctenophore. To test the hypothesis that the microbiota is genotypically selected for by the ctenophore host, experiments under controlled environments are required.

microbiology↗

bioRxiv2019

Continent-wide structure of bacterial microbiomes of European Drosophila melanogaster suggests host-control

The relative importance of host-control, environmental effects, and stochasticity in the assemblage of host-associated microbiomes has been much debated. With recent sampling efforts, the underpinnings of D. melanogasters microbiome structure have become tractable on larger spatial scales. We analyzed the microbiome among fly populations that were sampled across Europe by the European Drosophila Population Genomics Consortium (DrosEU). We combined environmental data on climate and food-substrate, dense genomic data on host population structure, and microbiome profiling. Food-substrate, temperature, and host population-structure correlated with microbiome-structure. The microbes, whose abundance was co-structured with host populations, also differed in abundance between flies and their substrate in an independent survey, suggesting host-control. Patterns of enrichment and depletion of microbes between host and substrate were consistent with a model of host-control, where the host manipulates its microbiome for its benefit. Putative host-control was bacterial strain specific, supporting recent evidence for high specificity of D. melanogaster-microbe interaction.

evolutionary biology↗

bioRxiv2018

Tarantula phylogenomics: A robust phylogeny of multiple tarantula lineages inferred from transcriptome data sheds light on the prickly issue of urticating setae evolution

Mygalomorph spiders of the family Theraphosidae, known to the broader public as tarantulas, are among the most recognizable arachnids on earth due to their large size and widespread distribution. Their use of urticating setae is a notable adaptation that has evolved exclusively in certain New World theraphosids. Thus far, the evolutionary history of Theraphosidae remains poorly understood; theraphosid systematics still largely relies on morphological datasets, which suffer from high degrees of homoplasy, and traditional targeted sequencing of preselected genes failed to provide strong support for supra-generic clades (i.e. particularly those broader than subfamilies). In this study, we provide the first robust phylogenetic hypothesis of theraphosid evolution inferred from transcriptome data. A core ortholog approach was used to generate a phylogeny from 2460 orthologous genes across 25 theraphosid genera, representing all of the major theraphosid subfamilies, except Selenogyrinae. For the first time our phylogeny recovers a monophyletic group that comprises the vast majority of New World theraphosid subfamilies including Aviculariinae and Theraphosinae. Concurrently, we provide additional evidence for the integrity of questionable subfamilies, such as Poecilotheriinae and Psalmopoeinae, and support the non-monophyly of Ischnocolinae. The deeper relationships between almost all subfamilies are confidently inferred for the first time. We also used our phylogeny in tandem with published morphological data to perform ancestral state analyses on urticating setae. This revealed that the evolution of this important defensive trait might be explained by three equally parsimonious scenarios.

evolutionary biology↗

bioRxiv2016

Bacterial but not protist gut microbiota align with ecological specialization in a set of lower termite species

The role of microbes in adaptation of higher organisms to the environment is becoming increasingly evident, but remains poorly understood. Protist and bacterial microbes facilitate that lower termites thrive on wood and are directly involved in substrate break down. During the course of evolution lower termites adapted to different diets and lifestyles. In order to test whether there are changes of the termite gut microbiota that co-occur and hence could be related to diet and lifestyle adaptation, we assessed the bacterial and protist communities in a multispecies framework profiling three wood-dwelling and two foraging lower termite species using 16S and 18S rRNA gene amplicon sequencing. Termites were kept under controlled conditions on the same diet to minimize environmental effects on their gut microbiota. We found that protist communities group according to host phylogeny while bacterial communities group according to lifestyle. The change from the ancestral wood-dwelling to a foraging lifestyle coincides with exposure to more diverse and higher concentrations of pathogens as well as a more diverse diet. Accordingly, we identified bacteria that are associated with foraging termites of the genus Reticulitermes and could function as probiotics or be metabolically important on a more diverse diet. Furthermore, protist and bacterial diversity are correlated, suggesting not only that many termite gut bacteria are associated with protists, but also suggesting a role of protist diversity in the evolution of bacterial diversity in the termite gut or vice versa.

evolutionary biology↗