Biology subjects

Szabo, G.

Publications and source records attributed to Szabo, G..

At least 19 recordsLinked to original sources

bioRxiv2026

Multiomic and Spatial Profiling of Colorectal Tissue Reveals Viral Persistence and Immune Dysregulation in Long COVID

Long COVID (LC) - a chronic condition characterized by persistent, debilitating symptoms following SARS-CoV-2 infection - has emerged as a major public health challenge. Although many interrelated mechanisms have been proposed as drivers of LC, the root causes have yet to be identified, posing significant challenges for therapeutic development. While many blood-based studies have been conducted, they have not yielded conclusive mechanistic insights into LC pathogenesis. Attention has therefore turned toward direct tissue investigation, with the gastrointestinal (GI) tract becoming a major focus due to evidence that virus or viral components can persist at this site for months to years following an episode of COVID-19. Here, we performed a high-dimensional characterization of colorectal tissue and peripheral blood in a highly characterized cohort of 44 people with LC and 13 recovered controls. We profiled SARS-CoV-2 persistence, host immune responses, and tissue inflammation using bulk and single-cell RNA sequencing, nCounter RNA probe hybridization, quantitative PCR, metagenomic next-generation sequencing, plasma proteomics, high-dimensional spectral flow cytometry, in situ-hybridization/immunohistochemistry, and single-cell digital spatial omics. Our results support a model in which LC is driven by long-term immune dysregulation and perturbations of the regulatory gut immune environment which imply ongoing viral persistence, although direct viral detection was only observed in a subset of participants. Specifically, we identify a tissue-based transcriptional environment in which SARS-CoV-2 activates innate myeloid immune signaling, driving chronic inflammation while simultaneously downregulating pathways responsible for immune-mediated clearance of infected cells, including antigen presentation, phagocytosis, cytotoxic immune cell trafficking, and granzyme production. Importantly, signatures in peripheral blood are considerably weaker than those observed in tissue. Together, these findings provide a direct biological rationale for therapeutic strategies in LC aimed at enhancing or redirecting cytotoxic immune function to overcome immune dysregulation and clear persistent viral reservoirs.

immunology↗

bioRxiv2025

Deficient processing of regularity violations during visuospatial neglect: a visual mismatch negativity study

Visuospatial neglect (VSN) after right-hemisphere stroke causes reduced engagement with left-sided stimuli, but how VSN affects automatic processes, i.e. the registration of regularities and regularity violations is still equivocal. This study investigated these processes using event-related potential components C1, C2/N1, and the visual mismatch negativity (vMMN), and how they differ in VSN compared to stroke and healthy controls, and their changes with time and rehabilitation. We applied a passive oddball paradigm, where diamond patterns periodically disappeared (OFF events) and reappeared (ON events) on the lower left and right sides, creating two simultaneous but independent sequences with standard and deviant events. The study included a VSN group (N=17, M=53.88{+/-}0.28 yrs); stroke patients (N=16, M = 56.81 {+/-} 13.26 yrs); and healthy participants (N=17, M=53.89{+/-}10.79 yrs). The VSN group underwent measurements three times: pre- and post-rehabilitation, and at a 4-month follow-up. Our results show that the C1 component emerged reliably in healthy participants and as a tendency in stroke controls, but not in VSN at any measurement point. The C2/N1 component emerged for all events without group differences. VSN patients showed no reliable vMMN, while it emerged in stroke patients for left-sided OFF events. Healthy controls showed vMMN in every condition. Our results suggest that both stroke and VSN impair the automatic detection of regularity violations, but VSN does so in a more substantial way, and this deficit does not improve with time or rehabilitation. Furthermore, the missing C1 component in VSN may indicate an early-stage deficiency even in visual processing.

neuroscience↗

bioRxiv2025

Digital Twin Approaches for Interpretable Side Effect Prediction in Drug Discovery

Artificial intelligence plays an ever-greater role in preclinical drug development, ranging from target identification and molecule design to ADME-Tox prediction; however, predicting side effects before performing clinical trials is still lagging behind. The best performing side effect predictors in the literature use either ATC codes, which are expert-derived features not even available at early stages, or graph neural networks based on chemical similarity, which - although use readily available features - are "black boxes" that do not deliver actionable insights. We argue that a paradigm shift is needed. Instead of using the latest neural network architectures that have proved worthy in other domains with a plethora of available data, one could use the off-targets of the compounds and build simple and interpretable predictors of side effects. To add another layer of biological realism, intricate biophysical mechanisms within the cells could also be simulated and used as features for training. Although not outperforming the current methods by a great margin, this digital twin-based model has the benefit of being interpretable, i.e., it puts biology behind the predictions. We showcase, with real-world examples, how the side effects predicted by this model can be interpreted and traced back to off-target proteins, and the complexes and signaling pathways in which they partake. In this way, the proposed model not only provides actionable insights, but in the future, may contribute to the amendment of secondary pharmacology assays. HighlightsO_LINo standard tool is available to predict side effects in early-phase drug discovery. C_LIO_LIAs publicly available side effect data is scarce, only simple models should be trained. C_LIO_LISimple models trained on biorealistic features, such as off-target proteins, are interpretable. C_LIO_LIInterpreting predictions can highlight critical off-targets and are therefore actionable. C_LI

pharmacology and toxicology↗

bioRxiv2025

A genomic catalog of Earth's bacterial and archaeal symbionts

1Microbial symbiosis drives the functional and phylogenomic diversification of life on Earth, yet remains underexplored due to culturing challenges. This study employed machine learning (ML) to predict symbiotic lifestyles in hundreds of thousands of microbial genomes from diverse environmental metagenome samples and reference genomes. Predictions were performed using symclatron, a novel ML framework developed here to identify genomic signatures of symbionts. Predictions were deposited in a novel Symbiont Genomes catalog (SymGs). The results indicated that 15-23% of uncultivated microbes likely engage in symbiotic relationships with other organisms and are present in half of all known bacterial and archaeal phyla. We also identified genomic signatures of symbiotic lifestyles, including the loss of certain metabolic functions and the differential presence of others that may enable host-dependent living. The symclatron software and the SymGs catalog represent valuable resources for studying symbioses, facilitating future mechanistic investigations of host-microbe associations.

genomics↗

bioRxiv2025

Phase transitions and symmetry breaking of cooperation on lattices

The donation game is an instance of a social dilemma with a single parameter given by the cost-to-benefit ratio of cooperation, r. In spatial settings limited local interactions and clustering are capable of supporting cooperation by reducing exploitation from defectors. Traditionally the interaction and competition neighbourhoods are identical. Here we discuss intriguing differences in the dynamics that arise when separating the neighbourhoods. On the square lattice disjoint interaction and competition neighbourhoods are easily realized by considering nearest neighbour interactions and second nearest neighbour competition. Incidentally, the number of first and second neighbours is the same. More importantly, this separates the population into two competing sub-populations, with interactions solely between sub-populations but competition within sub-populations. For negative cost-to-benefit ratios, r, the donation game turns into a harmony game and defection becomes an act of spite. In the traditional setup the extinction of cooperators under harsh conditions, large r, and that of spiteful defectors, r < 0, exhibits critical phase transitions with characteristics of directed percolation. In contrast, with two sub-populations spiteful behaviour cannot persist, while the extinction of cooperators exhibits the same characteristics. Most intriguingly, however, for smaller r spontaneous symmetry breaking in the levels of cooperation between the two sub-populations is observed. The symmetry breaking resembles the sub-lattice ordering occurring in the anti-ferromagnetic Ising model. Within the twofold degenerated phases, decreasing the cost-to-benefit ratio induces extremely large fluctuations (bursts) in the frequencies of cooperation. These bursts eventually drive the system into one of the absorbing states: occasionally homogeneous defection in both sub-lattices but usually only in one and homogeneous cooperation in the other, achieving perfect asymmetry. PACS numbers89.65.-s, 89.75.Fb, 87.23.Kg

evolutionary biology↗

bioRxiv2025

Tetranucleotide frequencies differentiate genomic boundaries and metabolic strategies across environmental microbiomes

Microbiomes are constrained by physicochemical conditions, nutrient regimes, and community interactions across diverse environments, yet genomic signatures of this adaptation remain unclear. Metagenome sequencing is a powerful technique to analyze genomic content in the context of natural environments, establishing concepts of microbial ecological trends. Here, we developed a data discovery tool - a tetranucleotide-informed metagenome stability diagram - that is publicly available in the Integrated Microbial Genomes and Microbiomes (IMG/M) platform for metagenome-ecosystem analyses. We analyzed the tetranucleotide frequencies from quality-filtered and unassembled sequence data of over 12,000 metagenomes to assess ecosystem-specific microbial community composition and function. We found that tetranucleotide frequencies can differentiate communities across various natural environments, and that specific functional and metabolic trends can be observed in this structuring. Our tool places metagenomes sampled from diverse environments into clusters and along gradients of tetranucleotide frequency similarity, suggesting microbiome community compositions specific to gradient conditions. Within the resulting metagenome clusters, we identify protein-coding gene identifiers that are most differentiated between ecosystem classifications. We plan for annual updates to the metagenome stability diagram in IMG/M with new data, allowing for refinement of the ecosystem classifications delineated here. This framework has the potential to inform future studies on microbiome engineering, bioremediation, and the prediction of microbial community responses to environmental change. ImportanceMicrobes adapt to diverse environments influenced by factors like temperature, acidity, and nutrient availability. We developed a new tool to analyze and visualize the genetic makeup of over 12,000 microbial communities, revealing patterns linked to specific functions and metabolic processes. This tool groups similar microbial communities and identifies characteristic genes within environments. By continually updating this tool, we aim to advance our understanding of microbial ecology, enabling applications like microbial engineering, bioremediation, and predicting responses to environmental change.

ecology↗

bioRxiv2024

miR-21: A therapeutic target for delaying severe liver disease and hepatocellular carcinoma in high-fat-diet-fed mice

Liver disease, including hepatocellular carcinoma (HCC), is a major global health concern, claiming approximately 2 million lives worldwide annually, yet curative treatments remain elusive. In this study, we aimed to investigate the role of microRNA-21-5p (miR-21) in metabolic dysfunction-associated steatotic liver disease (previously NAFLD), metabolic-associated steatohepatitis (previously NASH), and HCC within the context of a Western high-fat diet, without additional choline (HFD) and offering potential therapeutic insights. We found that reduced miR-21 levels correlated with liver disease progression in WT mice fed on HFD, while miR-21 knockout mice showed exacerbated metabolic dysfunction, including obesity, hepatomegaly, hyperglycemia, insulin resistance, steatosis, fibrosis, and HCC. Our study reveals that miR-21 plays a protective role in metabolic syndrome and in the progression of liver disease to cancer. MiR-21 directly targets Transforming growth factor beta-induced (Tgfbi), a gene also known to be significantly upregulated and a potential oncogene in HCC. Further, our study showed that intervention with the administration of a miR-21 mimic in WT livers effectively improves insulin sensitivity, steatosis, fibrosis, Tgfbi expression and tumor burden in HFD conditions. These findings indicate that miR-21 could serve as an effective strategy to delay or prevent liver disease in high-fat-diet environments. SignificanceOur study demonstrates in vivo that miR-21 has protective functions in the broad spectrum of high-fat diet-based, progressive liver disease and cancer, and we show potential therapeutic value of a microRNA-21 mimic. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=137 SRC="FIGDIR/small/613915v2_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@1915cd8org.highwire.dtl.DTLVardef@66887corg.highwire.dtl.DTLVardef@18a8e54org.highwire.dtl.DTLVardef@18631b0_HPS_FORMAT_FIGEXP M_FIG C_FIG

cancer biology↗

bioRxiv2024

Spontaneous symmetry breaking of cooperation between species

In mutualistic associations two species cooperate by exchanging goods or services with members of another species for their mutual benefit. At the same time competition for reproduction primarily continues with members of their own species. In intra-species interactions the prisoners dilemma is the leading mathematical metaphor to study the evolution of cooperation. Here we consider inter -species interactions in the spatial prisoners dilemma, where members of each species reside on one lattice layer. Cooperators provide benefits to neighbouring members of the other species at a cost to themselves. Hence, interactions occur across layers but competition remains within layers. We show that rich and complex dynamics unfold when varying the cost-to-benefit ratio of cooperation, r. Four distinct dynamical domains emerge that are separated by critical phase transitions, each characterized by diverging fluctuations in the frequency of cooperation: (i) for large r cooperation is too costly and defection dominates; (ii) for lower r cooperators survive at equal frequencies in both species; (iii) lowering r further results in an intriguing, spontaneous symmetry breaking of cooperation between species with increasing asymmetry for decreasing r; (iv) finally, for small r, bursts of mutual defection appear that increase in size with decreasing r and eventually drive the populations into absorbing states. Typically one species is cooperating and the other defecting and hence establish perfect asymmetry. Intriguingly and despite the symmetrical model setup, natural selection can nevertheless favour the spontaneous emergence of asymmetric evolutionary outcomes where, on average, one species exploits the other in a dynamical equilibrium.

evolutionary biology↗

bioRxiv2024

Effects of goldenrod (Solidago gigantea Aiton and S. canadensis L.) invasion on the wet meadow vegetation composition of Somogyfajsz wood pasture

In recent decades, restoring abandoned wood pastures are being rediscovered as an effective way to preserve biodiversity. Their restoration include the control of invasive plant species. In our study, we compared the vegetation composition of wet meadow patches uninvaded and invaded by giant and Canadian goldenrod in a wood pasture located in Somogyfajsz, Hungary. We sampled the vegetation of the wet meadows of the pasture in 16 pairs of 1 x 1 m invaded and uninvaded quadrats in June 2020. We studied the effect of goldenrod invasion on nature conservation value in terms of species diversity, origin of species, and Social Behaviour Types, and forage quality and quantity. The study revealed that goldenrod invasion had negative effects on species richness and community-level biomass in wet meadows, leading to a significant reduction in species diversity and total cover. Goldenrod invasion also impacted the richness and cover of both native and exotic species, with a decrease in richness but not cover, highlighting the competitive ability of goldenrods and their potential to alter vegetation composition.

ecology↗

bioRxiv2024

IRF3 regulates neuroinflammatory responses and the expression of genes associated with Alzheimer's disease.

The pathological role of interferon signaling is emerging in neuroinflammatory disorders, yet, the specific role of Interferon Regulatory Factor 3 (IRF3) in neuroinflammation remains poorly understood. Here, we show that global IRF3 deficiency delays TLR4-mediated signaling in microglia and attenuates the hallmark features of LPS-induced inflammation such as cytokine release, microglial reactivity, astrocyte activation, myeloid cell infiltration, and inflammasome activation. Moreover, expression of a constitutively active IRF3 (S388D/S390D:IRF3-2D) in microglia induces a transcriptional program reminiscent of the Activated Response Microglia and the expression of genes associated with Alzheimers Disease, notably apolipoprotein-e. Lastly, using bulk-RNAseq of IRF3-2D brain myeloid cells, we identified Z-DNA binding protein-1 as a target of IRF3 that is relevant across various neuroinflammatory disorders. Together, our results identify IRF3 as an important regulator of LPS-mediated neuroinflammatory responses and highlight IRF3 as a central regulator of disease-specific gene activation in different neuroinflammatory diseases.

neuroscience↗

bioRxiv2023

KDM4-dependent DNA breaks at active promoters facilitate +1 nucleosome eviction

When the effect of various posttranslational histone tail modifications (PTMs) on nucleosome stability was compared in an in situ assay involving agarose-embedded nuclei, the promoter proximal H3K4me3, H3K27ac and H4K8ac positive nucleosomes exhibited relative sensitivity to intercalators as compared to bulk H3-GFP or nucleosomes carrying any of the following marks: H3K27me1, H3K27me2, H3K27me3, H3K9me1, H3K9me2, H3K9me3, H3K36me3, H3K4me0, H3K4me1, H3K4me2, H3K9ac, and H3K14ac. Nickase or DNase I treatment of the nuclei, or bleomycin treatment of live cells, did not affect the stability of nucleosomes carrying H3K4me3 or H3K27ac, while those of the second group were all destabilized upon treatment with intercalators. These observations support the possibility that the promoter proximal marks specify dynamic nucleosomes accomodating relaxed DNA sequences due to DNA breaks generated in vivo. In line with this interpretation, endogeneous, 3OH nicks were mapped within the nucleosome free region of promoters controlling genes active in human mononuclear cells, a conclusion supported by superresolution colocalization studies. The +1 nucleosomes were stabilized and the incidence of nicks was decreased at the promoters upon KDM4a,b,c KO induction (Pedersen et al, EMBO J, 2016) in mouse embryonic stem cells (mES). While etoposide did not further destabilize +1 nucleosomes in control mES, their stabilized state in the KO state was reversed by the drug. A significant fraction of the DNA breaks comprises TOP2-generated nicks according to the results of molecular combing experiments. The chromatin regions harboring nicks are topologicaly separated from the domains containing superhelical chromatin. These observations lend support for a model where the role of DNA strand discontinuities in transcriptional regulation and in higher-order chromatin organization are integrated.

genetics↗

bioRxiv2023

Genomic refugium of pre-domestication lineages in the Bronze Age Carpathian Basin

Horse domestication is a key element in history for its impact on human mobility and warfare. There is clear evidence for horse control from the beginning of the 2nd millennium BCE in the Carpathian Basin, when antler cheekpieces appear in the archaeological record mostly in the eastern areas. Previous archaeogenomic studies also revealed that the spread of the ancestors of modern day horses began at this time period, but the details of this event in Bronze Age Europe is yet to be uncovered. In this study we report a new shotgun genome ([~]0.9x coverage) of a Middle Bronze Age horse (radiocarbon dated to 1740-1630 cal. BCE) from Tompa site, southern Hungary, along with six mitochondrial genomes from various sites from Late Copper Age to Early Bronze Age Western Hungary. Our results reveal a strong bottleneck among pre-domestication Carpathian Basin horses and delayed DOM2 introduction into the region compared to the surrounding areas. The population size reduction was most probably due to human mediated loss of natural habitat, but the practice of horsekeeping after the turn of the 2nd millennium BCE can not be excluded based on the genomic data. Our results provide a complex history for horse domestication in the Central-European region, highlighting the need for further research to fully understand the extent and nature of human-horse interactions in this area throughout prehistory.

evolutionary biology↗

bioRxiv2023

Hungarian Grey cattle grazing outperforms mowing during wet meadow restoration following plantation forest clear-cut

Land-use change and ecological invasion are two main drivers of biodiversity loss, and the restoration of semi-natural wet grasslands is needed to tackle invasive species and re-establish grassland biodiversity on former forest plantations. This study tested the effectiveness of two widely used management techniques (grazing by traditional Hungarian Grey cattle and mowing once a year in August) as a restoration method of wet meadows in a former forest plantation invaded by goldenrod species in Central Hungary. We compared the vegetation composition of grazed, mowed, and reference areas with semi-natural wet meadow vegetation based on plant biomass, species richness and cover of species groups of species origin, life span, growth form, and social behaviour types of Borhidi determining the grazing value and the nature conservation value of the grasslands. We found that grazing by Hungarian Grey cattle resulted in a vegetation that was more similar to the reference wet meadows than mowing once a year in late summer. Grazing was superior to mowing in terms of goldenrod control, total species richness and cover, as well as the abundance of natives, perennials, herbs, and legumes. However, in the grazed area, we detected more disturbance-tolerant and annual species than in the mowed area. Despite the improved vegetation condition in the grazed area, we identified substantial disparities between the grazed and reference areas after three years of grazing. Based on our results, we advise using continuous extensive grazing to restore and maintain semi-natural wet meadows.

ecology↗

bioRxiv2022

Gut Microbial Trimethylamine is Elevated in Alcohol-Associated Hepatitis and Contributes to Ethanol-Induced Liver Injury in Mice

BACKGROUNDThere is mounting evidence that microbes resident in the human intestine contribute to diverse alcohol-associated liver diseases (ALD) including the most deadly form known as alcohol-associated hepatitis (AH). However, mechanisms by which gut microbes synergize with excessive alcohol intake to promote liver injury are poorly understood. Furthermore, whether drugs that selectively target gut microbial metabolism can improve ALD has never been tested. METHODSWe used liquid chromatography tandem mass spectrometry to quantify the levels of microbe and host choline co-metabolites in healthy controls and AH patients, finding elevated levels of the microbial metabolite trimethylamine (TMA) in AH. In subsequent studies, we treated mice with non-lethal bacterial choline TMA lyase (CutC/D) inhibitors to blunt gut microbe-dependent production of TMA in the context of chronic ethanol administration. Indices of liver injury were quantified by complementary RNA sequencing, biochemical, and histological approaches. In addition, we examined the impact of ethanol consumption and TMA lyase inhibition on gut microbiome structure via 16S rRNA sequencing. RESULTSWe show the gut microbial choline metabolite trimethylamine (TMA) is elevated in AH patients and correlates with reduced hepatic expression of the TMA oxygenase flavin-containing monooxygenase 3 (FMO3). Provocatively, we find that small molecule inhibition of gut microbial CutC/D activity protects mice from ethanol-induced liver injury. CutC/D inhibitor-driven improvement in ethanol-induced liver injury is associated with distinct reorganization of the gut microbiome and host liver transcriptome. CONCLUSIONSThe microbial metabolite TMA is elevated in patients with AH, and inhibition of TMA production from gut microbes can protect mice from ethanol-induced liver injury.

biochemistry↗

bioRxiv2021

Consistent predictors of microbial community composition across scales in grasslands reveal low context-dependency

Environmental circumstances shaping soil microbial communities have been studied extensively, but due to disparate study designs it has been difficult to resolve whether a globally consistent set of predictors exists, or context-dependency prevails. Here, we used a network of 18 grassland sites (11 sampled across regional plant productivity gradients) to examine i) if the same abiotic or biotic factors predict both large- and regional-scale patterns in bacterial and fungal community composition, and ii) if microbial community composition differs consistently with regional plant productivity (low vs high) across different sites. We found that there is high congruence between predictors of microbial community composition across spatial scales; bacteria were predominantly associated with soil properties and fungi with plant community composition. Moreover, there was a microbial community signal that clearly distinguished high and low productivity soils that was shared across worldwide distributed grasslands suggesting that microbial assemblages vary predictably depending on grassland productivity.

ecology↗

bioRxiv2021

The cryptic gonadotropin-releasing hormone neuronal system of human basal ganglia

Human reproduction is controlled by [~]2,000 hypothalamic gonadotropin-releasing hormone (GnRH) neurons. Here we report the discovery and characterization of additional 150-200,000 GnRH-synthesizing cells in the human basal ganglia and basal forebrain. Extrahypothalamic GnRH neurons were cholinergic. Though undetectable in adult rodents, the GnRH-GFP transgene was expressed transiently by caudate-putamen cholinergic interneurons in newborn transgenic mice. In slice electrophysiological studies, GnRH inhibited these interneurons via GnRHR1 autoreceptors. Whole-transcriptome analysis of cholinergic interneurons and medium spiny projection neurons laser-microdissected from the human putamen confirmed selective expression of GNRH1 and GNRHR1 autoreceptors in cholinergic cells and uncovered the detailed transcriptome profile and molecular connectome of these two cell types. Higher- order non-reproductive functions regulated by GnRH under physiological conditions in the human basal ganglia and basal forebrain require clarification. GnRH/GnRHR1 signaling as a potential therapeutic target in the treatment of neurodegenerative disorders affecting cholinergic neurocircuitries, including Parkinsons and Alzheimers diseases, needs to be explored.

cell biology↗

bioRxiv2021

Fundamental Role Of The H2A.Z C-Terminal Tail In The Formation Of Constitutive Heterochromatin

H2A.Z-nucleosomes are present in both euchromatin and heterochromatin and it has proven difficult to interpret their disparate roles in the context of their stability features. Using an in situ assay of nucleosome stability and DT40 cells expressing engineered forms of the histone variant we show that native H2A.Z, but not C-terminally truncated H2A.Z (H2A.Z{Delta}C), is released from nucleosomes of peripheral heterochromatin at unusually high salt concentrations. H2A.Z and H3K9me3 landscapes are reorganized in H2A.Z{Delta}C-nuclei and overall sensitivity of chromatin to nucleases is increased. These tail-dependent differences are recapitulated upon treatment of HeLa nuclei with the H2A.Z-tail-peptide (C9), with MNase sensitivity being increased at specific regions including promoters. Introduced into live cells C9 elicits down-regulation of [~]560 genes with nonrandom chromosomal band-localization and pathway-spectrum. Thus, tail-dependent heterogeneity of H2A.Z-nucleosomes is revealed at all organization levels of chromatin and epigenetic modulation can be achieved by targeting molecular interactions involving its C-terminal tail.

cell biology↗

bioRxiv2020

Evolutionary recent dual obligatory symbiosis among adelgids indicates a transition between fungus and insect associated lifestyles

Adelgids (Insecta: Hemiptera: Adelgidae) form a small group of insects but harbor a surprisingly diverse set of bacteriocyte-associated endosymbionts, which suggest multiple replacement and acquisition of symbionts over evolutionary time. Specific pairs of symbionts have been associated with adelgid lineages specialized on different secondary host conifers. Using a metagenomic approach, we investigated the symbiosis of the Adelges laricis/tardus species complex containing betaproteobacterial ( Candidatus Vallotia tarda) and gammaproteobacterial ( Candidatus Profftia tarda) symbionts. Genomic characteristics and metabolic pathway reconstructions revealed that Vallotia and Profftia are evolutionary young endosymbionts, which complement each others role in essential amino acid production. Phylogenomic analyses and a high level of genomic synteny indicate an origin of the betaproteobacterial symbiont from endosymbionts of Rhizopus fungi. This evolutionary transition was accompanied with substantial loss of functions related to transcription regulation, secondary metabolite production, bacterial defense mechanisms, host infection and manipulation. The transition from fungus to insect endosymbionts extends our current framework about evolutionary trajectories of host-associated microbes.

microbiology↗