Biology subjects

Hubner, S.

Publications and source records attributed to Hubner, S..

13 recordsLinked to original sources

bioRxiv2026

The transposable elements syndrome of wheat domestication

Domestication marks a turning point in human history, driving substantial genomic modifications in cultivated plants. Tetraploid wheat was one of the Neolithic founder crops and remains a major cultivated species today. We investigated how domestication altered the abundance and distribution of transposable elements (TEs) and structural variation (SV) in wheat, revealing genomic changes associated with key domestication traits. Our results demonstrate that extensive TE proliferation before and during the Pleistocene-Holocene transition expanded standing genetic variation and phenotypic diversity. This expansion has provided the raw material for selection by the early farmers including a Gypsy insertion in the BTR1-3B gene causing a loss of function and contributing to the establishment of the non-shattering phenotype. We further show that purifying selection was more efficient in purging TEs among wild populations, whereas domesticated wheat has maintained TE clusters around genes that are under selection. We propose a model in which climatic instability triggered genome-wide TE bursts, expanding genetic variation including at domestication traits. As climate stabilized, purifying selection gradually removed deleterious TEs insertions, while early farmers selectively preserved advantageous phenotypes, thus maintaining TE-rich regions around key domestication genes. This model provides an integrative framework linking climate driven genomic changes, selection, divergence and domestication.

evolutionary biology↗

bioRxiv2025

Wild genes to the rescue: High-throughput genomics uncovers the wild source of broomrape resistance in sunflower

O_LIThe ongoing evolutionary arms race between crop plants and their parasites necessitates a constant exploration of new genetic resistance. Broomrape (Orobanche cumana), a devastating parasitic plant, presents a formidable challenge to sunflower production, yet the genetic mechanisms underlying host resistance are still largely unknown. C_LIO_LITo address this gap, we developed a high-throughput phenotyping platform to quantify root infestation in a highly diverse sunflower association mapping (SAM) population. Using a dual GWAS approach with both SNPs and k-mers, we were able to pinpoint the genetic basis of resistance. C_LIO_LIOur findings validate previously identified QTLs with greater resolution and reveal several novel candidate genes conferring resistance, including putative leucine-rich repeat receptor kinases. Critically, the k-mer mapping approach circumvented reference genome bias, highlighting key introgressions from wild Helianthus species that have contributed to broomrape resistance. C_LIO_LIThis research provides a powerful methodology for gene discovery and demonstrates that wild relatives remain a vital source of genetic material, offering breeders a significant advantage in the ongoing battle against rapidly evolving parasites. C_LI

plant biology↗

bioRxiv2024

Back to the Future: Environmental genomic selection to take advantage of polygenic local adaptation

The genetic basis of adaptation is a fundamental question in evolutionary genetics. Environmental association analysis (EAA) and various allele frequency comparisons in genomic environmental association (GEA) have become standard approaches for investigating the genetic basis of adaptation to natural environments. While these analyses provide insight into local adaptation, they have not been widely adopted in breeding or conservation programs. This may be attributable to the difficulty in identifying the best individuals for transplantation/relocation in conservation efforts or identification of the best parents in breeding programs. To explore the use of EAA and GEA for future breeding programs, we used a cereal crop - barley (Hordeum vulgare L.) as our case-study species due to its wide adaptability to different environments and agro-ecologies, ranging from marginal and low input fields to high-productive farms. Here, we use publicly available data to conduct environmental genomic selection (EGS) on 753 landrace barley accessions using a mini-core of 31 landrace accessions and a de-novo core of 100 as the training populations. Environmental genomic selection is to environmental association analysis (EAA) what genomic selection is to genome-wide association studies (GWAS). Since local adaptation to the environment is polygenic, a whole-genome approach is likely to be more accurate for selecting for environmental adaptation. Here we show distinct genetic background and population differences and how an integrative approach coupling environmental genomic selection and species distribution modelling can help identify key parents for breeding for adaptation to specific environmental variables and geographies to minimize linkage drag.

plant biology↗

bioRxiv2024

Shared selection and genetic architecture drive strikingly repeatable evolution in long-term experimental hybrid populations

The degree to which evolution repeats itself has implications regarding the major forces driving evolution and the potential for evolutionary biology to be a predictive (versus solely historical) science. To understand the factors that control evolutionary repeatability, we experimentally evolved four replicate hybrid populations of sunflowers at natural sites for up to 14 years and tracked ancestry across the genome. We found that there was very strong negative selection against introgressed ancestry in several chromosomes, but positive selection for introgressed ancestry in one chromosome. Further, the strength of selection was influenced by recombination rate. High recombination regions had lower selection against introgressed ancestry due to more frequent recombination away from incompatible backgrounds. Strikingly, evolution was highly parallel across replicates, with shared selection driving 88% of variance in introgressed allele frequency change. Parallel evolution was driven by both high levels of sustained linkage in introgressed alleles and strong selection on large-effect quantitative trait loci. This work highlights the repeatability of evolution through hybridization and confirms the central roles that natural selection, genomic architecture, and recombination play in the process.

evolutionary biology↗

bioRxiv2024

Transposable elements are entangled in rapid adaptation to climate change

Biodiversity conservation is urged at biodiversity hotspots that are under constant threat from anthropogenic development, yet a careful examination of the adaptive potential is a prerequisite for action. The Levant is considered a biodiversity hotspot and the distribution edge for many species, including important crop wild relatives. This region is under accelerated desertification and constantly disturbed by human activities, thus urging intervenient action. We collected and sequenced 300 wild barley plants along an eco-geographic gradient following a unique ecological-genetic sampling design. This scheme enabled to overcome the tight correlation between environmental and geographic distances. Phenotypic data was collected from 3600 progeny plants over three years and enabled to identify adaptive haplotype blocks comprised of phenological regulating genes tightly linked to drought and heat responsive genes. These haplotype blocks were highly enriched for transposable elements insertions, likely regulating genetic variation around adaptive genes, especially in stressed populations. Ecological and evolutionary models using over 2600 observations were combined to predict maladaptive risk, indicating that populations will be funneled into higher water availability refugia habitats while increasing isolation. Our findings highlight the main factors affecting rapid local adaptation and provide important recommendations for biodiversity management and conservation.

plant biology↗

bioRxiv2024

A STAT3 Degrader Demonstrates Pre-clinical Efficacy in Venetoclax resistant Acute Myeloid Leukemia

Acute myeloid leukemia (AML) is an aggressive hematologic malignancy that continues to have poor prognosis despite recent therapeutic advances. Venetoclax (Ven), a BCL2-inhibitor has shown a high response rate in AML; however, relapse is invariable due to mitochondrial dysregulation that includes upregulation of the antiapoptotic protein MCL1, a central mechanism of Ven resistance (Ven-res). We have previously demonstrated that the transcription factor STAT3 is upregulated in AML hematopoietic stem and progenitor cells (HSPCs) and can be effectively targeted to induce apoptosis of these aberrant cells. We now show that overexpression of STAT3 alone is sufficient to initiate a strong AML phenotype in a transgenic murine model. Phospho-proteomic data from Ven treated AML patients show a strong correlation of high total STAT3 and phospho-STAT3 [both p-STAT3(Y705) and p-STAT3(S727)] expression with worse survival and reduced remission duration. Additionally, significant upregulation of STAT3 was observed in Ven-res cell lines, in vivo models and primary patient samples. A novel and specific degrader of STAT3 demonstrated targeted reduction of total STAT3 and resulting inhibition of its active p-STAT3(Y705) and p-STAT3(S727) forms. Treatment with the STAT3 degrader induced apoptosis in parental and Ven-res AML cell lines and decreased mitochondrial depolarisation, and thereby dependency on MCL1 in Ven-res AML cell line, as observed by BH3 profiling assay. STAT3 degrader treatment also enhanced differentiation of myeloid and erythroid colonies in Ven-res peripheral blood mononuclear cells (PBMNCs). Upregulation of p-STAT3(S727) was also associated with pronounced mitochondrial structural and functional dysfunction in Ven-res cell lines, that were restored by STAT3 degradation. Treatment with a clinical-stage STAT3 degrader, KT-333 resulted in a significant reduction in STAT3 and MCL1 protein levels within two weeks of treatment in a cell derived xenograft model of Ven-res AML. Additionally, this treatment significant improvement in the survival of a Ven-res patient-derived xenograft in-vivo study. Degradation of STAT3 resulting in downregulation of MCL1 and improvements in global mitochondrial dysfunction suggests a novel mechanism of overcoming Ven-res in AML. Statement of PurposeFive-year survival from AML is dismal at 30%. Our prior research demonstrated STAT3 over-expression in AML HSPCs to be associated with inferior survival. We now explore STAT3 over-expression in Ven-res AML, explain STAT3 mediated mitochondrial perturbations and describe a novel therapeutic strategy, STAT3 degradation to overcome Ven-res.

cancer biology↗

bioRxiv2024

Advancing Thalamic Nuclei Segmentation: The Impact of Compressed Sensing and FastSurfer on MRI Processing

The thalamus is a collection of gray matter nuclei that play a crucial role in sensorimotor processing and modulation of cortical activity. Characterizing thalamic nuclei non-invasively with structural MRI is particularly relevant for patient populations with Parkinsons disease, epilepsy, dementia, and schizophrenia. However, severe head motion in these populations poses a significant challenge for in vivo mapping of thalamic nuclei. Recent advancements have leveraged the compressed sensing (CS) framework to accelerate structural MRI acquisition times in MPRAGE sequence variants, while fast segmentation tools like FastSurfer have reduced processing times in neuroimaging research. In this study, we evaluated thalamic nuclei segmentations derived from six different MPRAGE variants with varying degrees of CS acceleration (from about 9 to about 1 minute acquisitions), using both FreeSurfer and FastSurfer for segmentation. Our findings show minimal sequence effects with no systematic bias, and low volume variability across sequences for the whole thalamus and major thalamic nuclei. Notably, CS-accelerated sequences produced less variable volumes compared to non-CS sequences. Additionally, segmentations of thalamic nuclei by FreeSurfer and FastSurfer were highly comparable. We provide first evidence supporting that a good segmentation quality of thalamic nuclei with compressed sensing T1-weighted image acceleration in a clinical 3T MRI system is possible. Our findings encourage future applications of fast T1-weighted MRI to study deep gray matter. CS-accelerated sequences and rapid segmentation methods are promising tools for future studies aiming to characterize thalamic nuclei in vivo at 3T in both healthy individuals and clinical populations.

neuroscience↗

bioRxiv2024

Climate resilience conserved in global germplasm repositories: Picking the most promising parents for agile plant breeding

Crop diversity is an essential resource for national and international breeding programs aimed at preparing global agriculture for a changing climate to ensure global food security. To do this there are related risks that need to be evaluated (1) does the genetic diversity needed for climate adaptation exist somewhere? And (2) is such genetic diversity accessible? To evaluate these risks, we consider the test case of publicly available genotyped and georeferenced sorghum landraces (n = 1,937) to ask if diversity is sufficient to support breeding for climate change adaptation. Answering these questions allows for characterization of the best potential parents and the geographies that harbor the most potentially promising genetypes for crop improvement. We subset this data into national, regional, and global geographic regions, and complete/mini core collections to understand the potential for climate adaptation in regional germplasm. Study accessions were given a future climate resilience score based on future climatic projections and a genomic adaptive capacity score using genomic estimated adaptive values (GEAVs) generated from environmental genomic selection - EGS) to ask whether this accessible diversity stored in germplasm repositories is potentially sufficient to meet forecasted changes in growing environments under climate change. We find that genomic resilience capacity is highly variable among countries and regions. High geographical variability was also found for climate resilience. To equitably adapt agriculture to future climate conditions, increased accessibility to plant genetic resources is essential.

genomics↗

bioRxiv2022

The genomics of linkage drag in sunflower

Crop wild relatives represent valuable sources of alleles for crop improvement, including adaptation to climate change and emerging diseases. However, introgressions from wild relatives might have deleterious effects on desirable traits, including yield, due to linkage drag. Here we comprehensively analyzed the genomic and phenotypic impacts of wild introgressions into cultivated sunflower to estimate the impacts of linkage drag. First, we generated new reference sequences for seven cultivated and one wild sunflower genotype, as well as improved assemblies for two additional cultivars. Next, relying on previously generated sequences from wild donor species, we identified introgressions in the cultivated reference sequences, as well as the sequence and structural variants they contain. We then used a ridge regression model to test the effects of the introgressions on phenotypic traits in the cultivated sunflower association mapping population. We found that introgression has introduced substantial sequence and structural variation into the cultivated sunflower gene pool, including > 3,000 new genes. While introgressions reduced genetic load at protein-coding sequences and positively affected traits associated with abiotic stress resistance, they mostly had negative impacts on yield and quality traits. Introgressions found at high frequency in the cultivated gene pool had larger effects than low frequency introgressions, suggesting that the former likely were targeted by artificial selection. Also, introgressions from more distantly related species were more likely to be maladaptive than those from the wild progenitor of cultivated sunflower. Thus, pre-breeding efforts should focus, as far as possible, on closely related and fully compatible wild relatives.

genomics↗

bioRxiv2022

GWANN: Implementing deep learning in genome wide association studies

MotivationGenome wide association studies (GWAS) are extensively used across species to identify genes that underlie important traits. Most GWAS methods apply modifications and extensions to a linear regression model in order to detect significant associations between genetic variation and a trait. Despite their popularity, these statistical models tend to suffer from high false positive rates, especially when utilized on large variant datasets or complex demographic scenarios. To overcome this, aggressive statistical corrections are applied which frequently diminish true associations. ResultsHere we consider a deep learning approach, and present an implementation of a convolutional neural network (CNN) to identify genetic variation that is associated with a trait of interest. To exploit the strength of CNNs in visual recognition, the genotype information is represented as an image, which enables the model to correctly classify genetic variants with respect to the trait, even when a population structure is present. Our proposed approach was implemented in a package called GWANN which exhibited solid performance. Overall, GWANN outperformed popular GWAS tools on both simulated and real datasets, and enabled the identification of association signals with increased sensitivity and speed. Availability and implementationThe package is available at: https://github.com/hubner-lab/GWANN

bioinformatics↗

bioRxiv2022

Novel diversity panel facilitates genomic dissection of lodging in tef (Eragrostis tef)

RationalUnderutilized species that are not widely cultivated (known as orphan crops) present opportunities to increase crop diversity and food security. Tef [Eragrostis tef (Zucc.) Trotter] is known for its high-quality grain and forage. Root-borne lodging is a major devastating problem in tef cultivation, leading to large economic losses and limiting its widespread adoption. ObjectiveThe aim of this study was to identify genomic regions that are associated with tef lodging. MethodsA tef diversity panel (TDP-300) comprised of 297 lines was assembled, genotyped, and phenotyped across 4 field environments. This unique panel, the first of its kind in tef, has the potential to facilitate tef research and breeding. ResultsGenome-wide association study identified 29 sites associated with lodging; in all cases with a minor allele conferring reduced lodging. The eleven sites of prime interest were located in or near genes, 5 of them with a putative role, of which 3 were found to be involved root development. ConclusionsThe identification of lodging-related sites in the current study may advance understanding of the mechanisms underlying tef lodging and crop improvement. The identification of genes related to root development support the importance of root traits in tef lodging, which should be targeted in future breeding.

plant biology↗

bioRxiv2021

Decoupling the molecular regulation of perenniality and flowering in bulbous barley (Hordeum bulbosum)

Global crop production is being challenged by rapid population growth, declining natural resources, and dramatic climatic turnovers. These challenges have prompted plant breeders to explore new ventures to enhance adaptation and sustainability in crops. One intriguing approach to make agriculture more sustainable is by turning annual systems into perennial which offers many economic and biodiversity-friendly benefits. Previous attempts to develop a perennial cereal crop employed a classical breeding approach and extended over a long period with limited success. Thus, elucidating the genetic basis of perenniality at the molecular level can accelerate the breeding process. Here, we investigated the genetic basis of bulb formation in the barley congener species Hordeum bulbosum by elucidating the transcripts presence/absence variation compared with other annual species in the Poaceae, and a differential expression analysis of meristem tissues. The PAV analysis recaptured the expected phylogeny and indicated that H. bulbosum is enriched with developmental and disease responsive genes that are absent among annual species. Next, the abundance of transcripts was quantified and allowed to identify differentially expressed genes that are associated with bulb formation pathways in addition to major circadian clock genes that regulate flowering. A first model for the bulb formation pathway is suggested and include developmental and starch biosynthesis genes. To the best of our knowledge this is the first transcriptome developed for H. bulbosum and the first attempt to describe the regulation of bulb initiation in cereals at the molecular level.

plant biology↗

bioRxiv2021

Image processing and genome-wide association studies in sunflower identify loci associated with seed-coat characteristics

Sunflower seeds (technically achenes) are characterized by a wide spectrum of sizes, shapes, and colors. These traits are genetically correlated with the branching plant architecture loci, which were introgressed into restorer lines to facilitate efficient hybrid production. To break this genetic correlation between branching and seed traits, high resolution mapping of the genes that regulate seed traits is necessary. Recent progress in genomics permits acquisition of comprehensive genotyping data for a large diversity panel, yet a major constraint for exploring the genetic basis of important phenotypes across large diversity panels is the ability to screen and characterize them efficiently. Here, we implement a cost-effective image analysis pipeline to phenotype seed characteristics in a large sunflower diversity panel comprised of 287 individuals that represents most of the genetic variation in cultivated sunflower. A genome-wide association analysis was performed for seed-coat size and shape traits and significant signals were identified around genes regulating phytohormone activity. In addition, significant seed-coat color QTLs were identified and candidate genes that effect pigmentation were detected including a phytomelanin regulating gene on chromosome 17. Finally, QTLs associated with the seed-coat striped pattern were identified and phytohormone regulating candidate genes were detected. The implementation of image analysis phenotyping for GWAS allowed efficient screening of a large diversity panel and identification of valuable genetic factors effecting seed characteristics at the finest resolution to date.

genetics↗