Biology subjects

Gerber, D.

Publications and source records attributed to Gerber, D..

17 recordsLinked to original sources

bioRxiv2026

DPP9-mediated inflammasome repression protects against checkpoint inhibitor lung toxicity

Over one million patients receive cancer immunotherapy annually, yet the mechanisms underlying life-threatening immune-mediated toxicities remain poorly understood. Checkpoint inhibitor pneumonitis (CIP) is the leading cause of immunotherapy-related mortality, with a case fatality rate approaching 10%, and no genetic risk factors have been described to date. We identified Dipeptidyl-peptidase 9 (DPP9) as the first genetic susceptibility gene for CIP in a clinico-genomics cohort of 4,397 patients treated with immune checkpoint inhibitors. Mechanistically, DPP9 suppresses CARD8 inflammasome activation and IL-18 secretion in human monocytes, a pathway which is engaged prior to CIP onset, with IL-18 selectively elevated in the plasma of patients who subsequently develop CIP. Myeloid-restricted ablation of Dpp8 and Dpp9 in mice recapitulated the pulmonary histopathological and immunological hallmarks of CIP, including granuloma formation, accumulation of IFN{gamma}-producing T cells and monocyte-derived macrophages. Each of these phenotypes were driven by excessive IL-18 secretion. Together, these findings establish DPP9 as a genetic determinant of CIP and nominate IL-18 blockade as a mechanistically rational therapeutic strategy.

immunology↗

bioRxiv2026

Freshwater input and tidal position regulate species turnover and interaction rewiring in intertidal ecological networks

The effect that environmental conditions have on community and network assembly processes remains unclear, in part because these processes operate at multiple scales. Because marine primary producers and microinvertebrates have limited mobility, are susceptible to multiple stressors, and can be observed interacting in situ, their habitat-based interactions provide an informative system for disentangling network organising processes. We sampled 646 habitat-use networks, quantifying interactions involving habitat-users and biogenic habitat-formers over 12 months at 9 sites within Te Ihutai/Avon-Heathcote estuary in Christchurch, Aotearoa New Zealand. Using generalised dissimilarity mixed-effect models, we examined whether changes to species interactions - deconstructed into species turnover and interaction rewiring - were modulated by environmental covariates, including freshwater discharge, elevation, temperature, spatial location and season. We found that with increasing dissimilarity in sites proximity to freshwater, interaction change was more driven by rewiring, whereas differences in elevation (i.e., between channels and non-channel habitats) were driven by species turnover, with more sessile species inhabiting tidal channels. The proximity of habitats also played a strong role, with nearby networks comprising more similar interactions, and species turnover becoming more prevalent with increasing distance. Our results highlight that the relative influence and magnitude of rewiring and species turnover in controlling estuarine interaction networks was affected by the individual species distributions across the estuary and their responses to separate, but co-occurring, environmental factors. Quantification of habitat-former/user interaction networks offers robust, albeit understudied, measures of processes that can underpin community assembly, highlighting their potential importance in research, management and conservation. Open research statementData are provided for peer review. The code for produced from the project analysis and used to draft this manuscript is shared via a public GitHub repository hosted by the Tonkin Research group (repo name: EstInteractTurn). The data used in the formal analysis is hosted on Zenodo, under the corresponding authors profile (doi: 10.5281/zenodo.20619091). The data and code was prepared following strict adherence to the FAIR principles, meaning all data was saved as comma-separated values (.csv) or native R data structures (.rds).

ecology↗

bioRxiv2025

Evolutionary history and recurrent host adaptation in ancient Salmonella enterica

Salmonella enterica subsp. enterica is an extremely diverse bacterial pathogen causing frequent infections and foodborne disease among human populations. More than 1500 different bacterial strains (serovars) have been described, many with a wide host range. A small number of serovars are adapted to infect specific hosts: of these, serovars Typhi and Paratyphi A, B, and C cause primate-specific systemic infections (typhoid and paratyphoid fever). Although Paratyphi C is one of the rarest human-specific serovars today, it was once widespread, and all ancient Salmonella genomes published to date belong to or are ancestral to this lineage. Here, we present 53 new ancient Salmonella genomes spanning Eurasia and dating between 3500 BCE and 1300 CE. This rich genomic dataset allows us to reconstruct the evolutionary history of this pathogen in unprecedented detail. We identify multiple extinct prehistoric lineages that caused infections throughout Eurasia. Multiple lineage replacement events are observed throughout prehistoric and historic times, and Bayesian phylogenetic analysis is used to date and identify host adaptation events within this lineage. We find that host-adapted sublineages Paratyphi C, Choleraesuis, and Typhisuis continued to evolve host specificity independently from each other. We reconstruct signals of convergent host adaptation in the studied lineages and other host-adapted strains by analysing shared pseudogenes and recurrent gene gain and loss events. This analysis demonstrates a role for host interactions as a particular target of selection, highlighting the gradual adaptation of this S. enterica lineage to humans that coincides with the intensification of animal husbandry in pastoralist and sedentary farming societies.

genetics↗

bioRxiv2024

Ice and air: Visualisation of freeze-thaw embolism and freezing spread in young L. tulipifera leaves

Spring freezing is an unforgiving stress for young leaves, often leading to death, with consequences for tree productivity and survival. While both the plant water transport system and living tissues are vulnerable to freezing, we do not know whether damage to one or both of these systems causes death in leaves exposed to freezing. Whole saplings of Liriodendron tulipifera were exposed to freezing and thawing trajectories designed to mimic natural spring freezes. We monitored the formation of freeze-thaw xylem embolism and damage to photosynthetic tissues to reveal a predictable progression of ice formation across the leaf surface that is strongly influenced by leaf vein architecture, notably the presence or absence of bundle sheath extensions. Our data also show that freeze-thaw embolism occurs only in the largest vein orders where mean vessel diameter exceeds 30{micro}m. With evidence of both freeze-thaw embolism and damage to photosynthetic tissue, we conclude that this dual-mode lethality may be common among other wide-vesseled angiosperm-leaves, potentially playing a role in limiting geographic distributions, and show that bundle sheath extensions may stall or even prevent freezing spread. HighlightBoth ice and air lead likely lead to death in young L.tulipfera leaves exposed to freezing, with the spread of both governed by physical characteristics of these leaves.

physiology↗

bioRxiv2024

Ancient genomes reveal Avar-Hungarian transformations in the 9-10th centuries CE in the Carpathian Basin

During the Early Medieval period, the Carpathian Basin witnessed significant demographic shifts, notably under the Avar dominance for approximately 250 years, followed by the settlement of early Hungarians in the region during the late 9th century CE. This study presents the genetic analysis of 296 ancient samples, including 103 shotgun-sequenced genomes, from present-day Western Hungary. By employing identity-by-descent (IBD) segment sharing networks, this research offers detailed insights into the population structure and dynamics of the region from the 5th to the 11th centuries CE, with specific focus on certain microregions. Our evaluations reveal spatially different histories in Transdanubia even between communities in close geographical proximity, highlighting the importance of dense sampling and analyses. Our findings highlight extensive homogenisation and reorganization processes, discontinuities between Hun, Avar, and Conquest period immigrant groups, alongside the spread and integration of ancestry related to the Hungarian conquerors. TeaserGenetic formation of medieval Hungary, discontinuity between immigrant groups in the first millennium CE

genomics↗

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↗

bioRxiv2022

High Coverage Mitogenomes and Y-Chromosomal Typing Reveal Ancient Lineages in the Modern-day Szekely Population in Romania

Here we present 115 whole mitogenomes and 92 Y-chromosomal STR and SNP profiles from a Hungarian ethnic group, the Szekelys (in Romanian: Secuii, in German: Sekler) living in southeast Transylvania (Romania). The Szekelys can be traced back to the 12th century in the region, and numerous scientific theories exist as to their origin. We carefully selected sample providers that had local ancestors inhabiting small villages in the area of Odorheiu Secuiesc/Szekelyudvarhely in Romania. The results of our research and the reported data signify a qualitative leap compared to previous studies, since complete mitochondrial DNA sequences and Y-chromosomal data containing 23 STRs have not been available from the region until now. We evaluated the results with population genetic and phylogenetic methods, in the context of the modern and ancient populations that are either geographically or historically related to the Szekelys. Our results demonstrate a predominantly local uniparental make-up of the population that also indicates limited admixture with neighbouring populations. Phylogenetic analyses confirmed the presumed eastern origin of certain maternal (A, C, D) and paternal (Q, R1a) lineages and, in some cases, they could also be linked to ancient DNA data from Migration Period (5th-9th centuries AD) and Hungarian Conquest Period (10th century AD) populations.

genetics↗

bioRxiv2022

Tracing genetic connections of ancient Hungarians to the 6-14th century populations of the Volga-Ural region

Most of the early Hungarian tribes originated from the Volga-Kama and South-Ural regions, where they were composed of a mixed population based on historical, philological, and archaeological data. We present here the uniparental genetic makeup of the medieval era of these regions that served as a melting pot for ethnic groups with different linguistic and historical backgrounds. Representing diverse cultural contexts, the new genetic data originates from ancient proto-Ob-Ugric people from Western Siberia (6th-13th century), the pre-Conquest period, and subsisting Hungarians from the Volga-Ural region (6th-14th century) and their neighbours. By examining the eastern archaeology traits of Hungarian prehistory, we also study their genetic composition and origin in an interdisciplinary framework. We analysed 110 deep-sequenced mitogenomes and 42 Y-chromosome haplotypes from 18 archaeological sites in Russia. The results support the studied groups genetic relationships regardless of geographical distances, suggesting large-scale mobility. We detected long-lasting genetic connections between the sites representing the Kushnarenkovo and Chiyalik cultures and the Carpathian Basin Hungarians and confirmed the Uralic transmission of several East-Eurasian uniparental lineages in their genepool. Based on phylogenetics, we demonstrate and model the connections and splits of the studied Volga-Ural and conqueror groups. Early Hungarians and their alliances conquered the Carpathian Basin around 890 AD. Re-analysis of the Hungarian conquerors maternal genepool reveals numerous surviving maternal relationships in both sexes; therefore, we conclude that men and women came to the Carpathian Basin together, and although they were subsequently genetically fused into the local population, certain eastern lineages survived for centuries.

genetics↗

bioRxiv2022

Interdisciplinary analyses of Bronze Age communities from Western Hungary reveal complex population histories

In this study we report 21 ancient shotgun genomes from present-day Western Hungary, from previously understudied Late Copper Age Baden, and Bronze Age Somogyvar-Vinkovci, Kisapostag, and Encrusted Pottery archaeological cultures (3530 - 1620 cal BCE). Our results indicate the presence of high steppe ancestry in the Somogyvar-Vinkovci culture. They were then replaced by the Kisapostag group, who exhibit an outstandingly high (up to [~]47%) Mesolithic hunter-gatherer ancestry, despite this component being thought to be highly diluted by the time of the Early Bronze Age. The Kisapostag population contributed the genetic basis for the succeeding community of the Encrusted pottery culture. We also found an elevated hunter-gatherer component in a local Baden culture associated individual, but no connections were proven to the Bronze Age individuals. The hunter-gatherer ancestry in Kisapostag is likely derived from two main sources, one from a Funnelbeaker or Globular Amphora culture related population and one from a previously unrecognised source in Eastern Europe. We show that this ancestry not only appeared in various groups in Bronze Age Central Europe, but also made contributions to Baltic populations. The social structure of Kisapostag and Encrusted pottery cultures is patrilocal, similarly to most contemporaneous groups. Furthermore, we developed new methods and method standards for computational analyses of ancient DNA, implemented to our newly developed and freely available bioinformatic package. By analysing clinical traits, we found carriers of aneuploidy and inheritable genetic diseases. Finally, based on genetic and anthropological data, we present here the first female facial reconstruction from the Bronze Age Carpathian Basin.

genomics↗

bioRxiv2021

Protein degradation analysis by affinity microfluidics

Protein degradation mediated by the ubiquitin-proteasome pathway regulates signaling events in all eukaryotic cells, with implications in pathological conditions such as cancer and neurodegenerative diseases. Detection of protein degradation is an elementary need in basic and translational research. In vitro degradation assays, in particular, have been instrumental in the understanding of how cell proliferation and other fundamental cellular processes are regulated. These assays are direct, quantitative and highly informative but also laborious, typically relying on low-throughput polyacrylamide gel-electrophoresis followed by autoradiography or immunoblotting. We present protein degradation on chip (pDOC), a MITOMI-based integrated microfluidic device for discovery and analysis of ubiquitin-mediated proteolysis. The platform accommodates microchambers on which protein degradation is assayed quickly and simultaneously in physiologically relevant environments, using minute amount of reagents. Essentially, pDOC provides a multiplexed, sensitive and colorimetric alternative to the conventional degradation assays, with relevance to biomedical and translational research.

bioengineering↗

bioRxiv2021

Targeting de novo lipogenesis and the Lands cycle induces ferroptosis in KRAS-mutant lung cancer

Mutant KRAS (KM) is the most common oncogene in lung cancer (LC). KM regulates several metabolic networks, but their role in tumorigenesis is still not sufficiently characterized to be exploited in cancer therapy. To identify metabolic networks specifically deregulated in KMLC, we characterized the lipidome of genetically engineered LC mice, cell lines, patient derived xenografts and primary human samples. We also determined that KMLC, but not EGFR-mutant (EGFR-MUT) LC, is enriched in triacylglycerides (TAG) and phosphatidylcholines (PC). We also found that KM upregulates fatty acid synthase (FASN), a rate-limiting enzyme in fatty acid (FA) synthesis promoting the synthesis of palmitate and PC. We determined that FASN is specifically required for the viability of KMLC, but not of LC harboring EGFR-MUT or wild type KRAS. Functional experiments revealed that FASN inhibition leads to ferroptosis, a reactive oxygen species (ROS)-and iron-dependent cell death. Consistently, lipidomic analysis demonstrated that FASN inhibition in KMLC leads to accumulation of PC with polyunsaturated FA (PUFA) chains, which are the substrate of ferroptosis. Integrating lipidomic, transcriptome and functional analyses, we demonstrated that FASN provides saturated (SFA) and monounsaturated FA (MUFA) that feed the Lands cycle, the main process remodeling oxidized phospholipids (PL), such as PC. Accordingly, either inhibition of FASN or suppression of the Lands cycle enzymes PLA2 and LPCAT3, promotes the intracellular accumulation of lipid peroxides and ferroptosis in KMLC both in vitro and in vivo. Our work supports a model whereby the high oxidative stress caused by KM dictates a dependency on newly synthesized FA to repair oxidated phospholipids, establishing a targetable vulnerability. These results connect KM oncogenic signaling, FASN induction and ferroptosis, indicating that FASN inhibitors already in clinical trial in KMLC patients (NCT03808558) may be rapidly deployed as therapy for KMLC.

cancer biology↗

bioRxiv2020

Seagrass beds provide habitat for crabs, shrimps and fish in two estuaries on the South Island of New Zealand

O_LISeagrasses are marine angiosperms that potentially provide habitat for crabs, shrimps and fish. However, these types of data are lacking for the seagrass species (Zostera muelleri/rimur[e]hia) that inhabit intertidal estuaries on the South Island of New Zealand. C_LIO_LIAbundances of crabs, shrimps and fish were therefore quantified from 361 non-destructive seine tows done in seagrass beds and bare mudflats in Duvauchelle bay and two sites in the Avon-Heathcote/Ihutai estuary between October 2019 and February 2020. C_LIO_LIA total of 2549 crabs, 5824 shrimps and 1149 fish (75% were juvenile flounders) were identified and counted in the seine-net and immediately released back in healthy condition to the exact location from where they were caught. C_LIO_LIOnly few seagrass leaves were caught in the net and these leaves may have been previously uprooted drift fragments. The instant catch-and-release methodology therefore leaves, literally, nothing but a footprint. C_LIO_LIMore fish taxa, including two species of pipefish, were found in seagrass beds in Duvauchelle bay than in the Avon-Heathcote estuary. Fish (minus juvenile flounders) were also more abundant in these seagrass beds. Furthermore, juvenile flounders and shrimps were more abundant in Duvauchelle bay compared to the Avon-Heathcote estuary, but were found in similar abundances in seagrass beds and on bare flats. C_LIO_LIIt is possible that more fish were found in Duvauchelle seagrass beds because these beds have adjacent deeper areas, and may have high connectivity to seagrass beds in nearby bays. This hypothesis should be tested by sampling more seagrass beds in different types of estuaries and bays. C_LIO_LIBy contrast, crabs were more abundant in the Avon-Heathcote estuary, where spider crabs were most abundant in the seagrass beds, but other crabs were found in similar abundances in seagrass beds and bare habitat. We hypothesize that crab abundances were higher in the Avon-Heathcote estuary because of lower fish predation pressure and/or larger populations of prey like mollusc and polychaetes. C_LIO_LIOur results suggests that (a) superficially similar Zostera beds in relatively close proximity can provide very different habitat values for fish and crustaceans, (b) seagrass beds with higher diversity and abundances of fish may be prioritized in conservation and management (assuming other important ecosystem functions are similar between beds), and (c) that pipefish may be useful indicator organisms, representing healthy, extensive, dense and connected seagrass beds. C_LI O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=177 SRC="FIGDIR/small/120055v1_ufig1.gif" ALT="Figure 1"> View larger version (111K): org.highwire.dtl.DTLVardef@1c21731org.highwire.dtl.DTLVardef@180c521org.highwire.dtl.DTLVardef@10e2875org.highwire.dtl.DTLVardef@824c21_HPS_FORMAT_FIGEXP M_FIG C_FIG

ecology↗

bioRxiv2020

Early Medieval Genetic Data from Ural Region Evaluated in the Light of Archaeological Evidence of Ancient Hungarians

The ancient Hungarians originated from the Ural region of Russia, and migrated through the Middle-Volga region and the Eastern European steppe into the Carpathian Basin during the 9th century AD. Their Homeland was probably in the southern Trans-Ural region, where the Kushnarenkovo culture disseminated. In the Cis-Ural region Lomovatovo and Nevolino cultures are archaeologically related to ancient Hungarians. In this study we describe maternal and paternal lineages of 36 individuals from these regions and nine Hungarian Conquest period individuals from todays Hungary, as well as shallow shotgun genome data from the Trans-Uralic Uyelgi cemetery. We point out the genetic continuity between the three chronological horizons of Uyelgi cemetery, which was a burial place of a rather endogamous population. Using phylogenetic and population genetic analyses we demonstrate the genetic connection between Trans-, Cis-Ural and the Carpathian Basin on various levels. The analyses of this new Uralic dataset fill a gap of population genetic research of Eurasia, and reshape the conclusions previously drawn from 10-11th century ancient mitogenomes and Y-chromosomes from Hungary.

genetics↗

bioRxiv2019

Cell cycle oscillators underlying orderly proteolysis of E2F8

E2F8 is a transcriptional repressor that antagonizes the canonical cell cycle transcription factor E2F1. Despite the importance of this atypical E2F family member in cell cycle, apoptosis and cancer, we lack a complete description of the mechanisms that control its dynamics. To address this question, we developed a complementary set of static and dynamic cell-free systems of human origin, which recapitulate inter-mitotic and G1 phases, and a full transition from pro-metaphase to G1. This revealed an interlocking molecular switch controlling E2F8 degradation at mitotic exit, involving dephosphorylation of Cdk1 sites in E2F8 and the activation of APC/CCdh1, but not APC/CCdc20. Further, we revealed a differential stability of E2F8, accounting for its accumulation in late G1 while APC/CCdh1 is still active and suggesting a key role for APC/C in controlling G1-S transcription. Finally, we identified SCF-Cyclin F as the ubiquitin ligase controlling E2F8 in G2-phase. Altogether, our data provide new insights into the regulation of E2F8 throughout the cell cycle, illuminating an extensive coordination between phosphorylation, ubiquitination and transcription in promoting orderly cell cycle progression.

cell biology↗

bioRxiv2018

Inner Asian maternal genetic origin of the Avar period nomadic elite in the 7th century AD Carpathian Basin

After 568 AD the nomadic Avars settled in the Carpathian Basin and founded their empire, which was an important force in Central Europe until the beginning of the 9th century AD. The Avar elite was probably of Inner Asian origin; its identification with the Rourans (who ruled the region of todays Mongolia and North China in the 4th-6th centuries AD) is widely accepted in the historical research.\n\nHere, we study the whole mitochondrial genomes of twenty-three 7th century and two 8th century AD individuals from a well-characterised Avar elite group of burials excavated in Hungary. Most of them were buried with high value prestige artefacts and their skulls showed Mongoloid morphological traits.\n\nThe majority (64%) of the studied samples mitochondrial DNA variability belongs to Asian haplogroups (C, D, F, M, R, Y and Z). This Avar elite group shows affinities to several ancient and modern Inner Asian populations.\n\nThe genetic results verify the historical thesis on the Inner Asian origin of the Avar elite, as not only a military retinue consisting of armed men, but an endogamous group of families migrated. This correlates well with records on historical nomadic societies where maternal lineages were as important as paternal descent.

genomics↗

bioRxiv2018

Development and Validation of a Nomogram Prognostic Model for Small-Cell Lung Cancer Patients

BackgroundSmall-cell lung cancer (SCLC) accounts for almost 15% of lung cancer cases in the United States. Nomogram prognostic models could greatly facilitate risk stratification and treatment planning, as well as more refined enrollment criteria for clinical trials. We developed and validated a new nomogram prognostic model for SCLC patients using a large SCLC patient cohort from the National Cancer Database (NCDB).\n\nMethodsClinical data of 24,680 SCLC patients diagnosed from 2004 to 2011 were used to develop the nomogram prognostic model. The model was then validated using an independent cohort of 9,700 SCLC patients diagnosed from 2012 to 2013. The prognostic performance was evaluated using p value, concordance index and integrated Area Under the (time dependent Receiver Operating Characteristic) Curve.\n\nResultsThe following variables were contained in the final prognostic model: age, gender, race, ethnicity, Charlson/Deyo Score, TNM Stage (assigned according to the AJCC 8th edition), treatment type (combination of surgery, radiation therapy and chemotherapy), and laterality. The model was validated in an independent testing group with a concordance index of 0.722 {+/-} 0.004 and an integrated AUC of 0.79. The nomogram model has a significantly higher prognostic accuracy than previously developed models, including the AJCC 8th edition TNM-staging system. We implemented the proposed nomogram and two previously published nomograms in an online webserver.\n\nConclusionsWe developed a nomogram prognostic model for SCLC patients, and validated the model using an independent patient cohort. The nomogram performs better than earlier models, including AJCC staging.

cancer biology↗

bioRxiv2017

Multiple hidden processes complicate phylogenomic inference of deep Basidiomycota relationships

Resolving deep divergences in the fungal tree of life remains a challenging task even for analyses of genome-scale phylogenetic datasets. Relationships between Basidiomycota subphyla, the rusts (Pucciniomycotina), smuts (Ustilaginomycotina) and mushroom forming fungi (Agaricomycotina) represent a particularly challenging situation that posed problems to both traditional multigene and genome-scale phylogenetic studies. Here, we address basal Basidiomycota relationships using three different phylogenomic datasets, concatenated and gene tree-based analyses and examine the contribution of several potential sources of uncertainty, including fast-evolving sites, putative long-branch taxa, model violation and missing data. We inferred conflicting results with different datasets and under different models. Fast-evolving sites and oversimplified models of amino acid substitution favored the grouping of smuts with mushroom-forming fungi, often leading to maximal bootstrap support in both concatenation and Astral analyses. The most conserved datasets grouped rusts with mushroom forming fungi, although this relationship proved labile, sensitive to model choice, different data subsets and missing data. Excluding putative long branch taxa, genes with the highest proportions of missing data and/or genes with strong signal failed to reveal a consistent trend toward one or the other topology, suggesting that additional sources of conflict are at play too. Our analyses suggest that topologies uniting smuts with mushroom forming fungi can arise as a result of inappropriate modeling of amino acid sites that might be prone to systematic bias. While concatenated analyses yielded strong but conflicting support, individual gene trees mostly provided poor support for rusts, smuts and mushroom-forming fungi, suggesting that the true Basidiomycota tree might be in a part of the tree space that is difficult to access using both concatenation and gene tree based approaches. Thus, basal Basidiomycota relationships remain unresolved and might represent a phylogenetic problem that remains contentious even in the genomic era.

evolutionary biology↗