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INFLUENCE OF ACTN3 GENE ON MUSCLE HEALTH AND PHYSICAL FITNESS TO INFORM FUTURE INTERVENTIONS IN SPACEFLIGHT MISSIONS

INTRODUCTION: Exposure to reduced gravity environments leads to diminished muscle size, strength, and endurance. Preservation of physical fitness is critical for mission essential tasks such as extravehicular activities or adaptation to changes in gravity loads. Current countermeasures to maintain ISS astronauts’ muscle mass and fitness include dedicated time for a combination of cardiovascular exercise and resistance training. Countermeasure effectiveness is monitored through VO2 max and isometric mid-thigh pulls. It is important to understand both environmental and genetic contributors to astronaut physical fitness. Multiple genes, including ACTN3, are known to correlate with exercise phenotypes and have the potential to help personalize countermeasures based on an astronaut’s genotypic makeup. TOPIC: The ACTN3 gene encodes a protein expressed only in fast-twitch muscles and correlates with sprint and power phenotypes. A common polymorphism in ACTN3 gene is R577X (rs1815739), produced by a C−to−T base substitution resulting in a nonsense mutation from arginine (R) to a premature stop codon (X) present in approximately 18% of the population. This polymorphism causes an absence of α−actinin−3 in type II muscle fibers but does not lead to a disease phenotype. The RR genotype is associated with elite athletes, especially in sprint and power sports. The XX genotype is believed to be more common in endurance athletes. The ACTN3 gene also has potential associations with training adaptation, post-exercise recovery, and exercise-associated injuries. APPLICATION: Understanding how ACTN3 and other genetic determinates of fitness phenotypes affect astronaut physical performance can inform personalized exercise and recovery prescriptions. For example, individuals with the RR or RX genotype may respond better to high-load and low repetition exercise, while XX may benefit from high repetition with low weight exercise. Since the wild-type protein may confer more resistance to muscle damage, those individuals with the RR or RX genotype may benefit from high intensity interval training for improved VO2 max, whereas those with an XX genotype may benefit from low intensity, high volume endurance activity. Additionally, omics data related to health and performance could be used as biomarkers to monitor astronaut fitness and the effectiveness of training regimens during a mission. Learning objectives: • Learn about the phenotypic effects on muscle function and fitness secondary to R577X mutation in the ACTN3 gene • Learn how mutations in the ACTN3 gene may inform future countermeasures for future spaceflight missions

Lynn K Stanwyck↗

DOE OSTI2023

PhytoOracle: Scalable, modular phenomics data processing pipelines

As phenomics data volume and dimensionality increase due to advancements in sensor technology, there is an urgent need to develop and implement scalable data processing pipelines. Current phenomics data processing pipelines lack modularity, extensibility, and processing distribution across sensor modalities and phenotyping platforms. To address these challenges, we developed PhytoOracle (PO), a suite of modular, scalable pipelines for processing large volumes of field phenomics RGB, thermal, PSII chlorophyll fluorescence 2D images, and 3D point clouds. PhytoOracle aims to ( i ) improve data processing efficiency; ( ii ) provide an extensible, reproducible computing framework; and ( iii ) enable data fusion of multi-modal phenomics data. PhytoOracle integrates open-source distributed computing frameworks for parallel processing on high-performance computing, cloud, and local computing environments. Each pipeline component is available as a standalone container, providing transferability, extensibility, and reproducibility. The PO pipeline extracts and associates individual plant traits across sensor modalities and collection time points, representing a unique multi-system approach to addressing the genotype-phenotype gap. To date, PO supports lettuce and sorghum phenotypic trait extraction, with a goal of widening the range of supported species in the future. At the maximum number of cores tested in this study (1,024 cores), PO processing times were: 235 minutes for 9,270 RGB images (140.7 GB), 235 minutes for 9,270 thermal images (5.4 GB), and 13 minutes for 39,678 PSII images (86.2 GB). These processing times represent end-to-end processing, from raw data to fully processed numerical phenotypic trait data. Repeatability values of 0.39-0.95 (bounding area), 0.81-0.95 (axis-aligned bounding volume), 0.79-0.94 (oriented bounding volume), 0.83-0.95 (plant height), and 0.81-0.95 (number of points) were observed in Field Scanalyzer data. We also show the ability of PO to process drone data with a repeatability of 0.55-0.95 (bounding area).

59 BASIC BIOLOGICAL SCIENCES↗

NASA NTRS2002

Abundant raw material for cis-regulatory evolution in humans

Changes in gene expression and regulation--due in particular to the evolution of cis-regulatory DNA sequences--may underlie many evolutionary changes in phenotypes, yet little is known about the distribution of such variation in populations. We present in this study the first survey of experimentally validated functional cis-regulatory polymorphism. These data are derived from more than 140 polymorphisms involved in the regulation of 107 genes in Homo sapiens, the eukaryote species with the most available data. We find that functional cis-regulatory variation is widespread in the human genome and that the consequent variation in gene expression is twofold or greater for 63% of the genes surveyed. Transcription factor-DNA interactions are highly polymorphic, and regulatory interactions have been gained and lost within human populations. On average, humans are heterozygous at more functional cis-regulatory sites (>16,000) than at amino acid positions (<13,000), in part because of an overrepresentation among the former in multiallelic tandem repeat variation, especially (AC)(n) dinucleotide microsatellites. The role of microsatellites in gene expression variation may provide a larger store of heritable phenotypic variation, and a more rapid mutational input of such variation, than has been realized. Finally, we outline the distinctive consequences of cis-regulatory variation for the genotype-phenotype relationship, including ubiquitous epistasis and genotype-by-environment interactions, as well as underappreciated modes of pleiotropy and overdominance. Ordinary small-scale mutations contribute to pervasive variation in transcription rates and consequently to patterns of human phenotypic variation.

NASA Discipline Evolutionary Biology↗

NASA NTRS1999

Non-unity molecular heritability demonstrated by continuous evolution in vitro

INTRODUCTION: When catalytic RNA is evolved in vitro, the molecule's chemical reactivity is usually the desired selection target. Sometimes the phenotype of a particular RNA molecule cannot be unambiguously determined from its genotype, however. This can occur if a nucleotide sequence can adopt multiple folded states, an example of non-unity heritability (i.e. one genotype gives rise to more than one phenotype). In these cases, more rounds of selection are required to achieve a phenotypic shift. We tested the influence of non-unity heritability at the molecular level by selecting for variants of a ligase ribozyme via continuous evolution. RESULTS: During 20 bursts of continuous evolution of a 152-nucleotide ligase ribozyme in which the Mg2+ concentration was periodically lowered, a nine-error variant of the starting 'wild-type' molecule became dominant in the last eight bursts. This variant appears to be more active than the wild type. Kinetic analyses of the mutant suggest that it may not possess a higher first-order catalytic rate constant, however. Examination of the multiple RNA conformations present under the continuous evolution conditions suggests that the mutant is superior to the wild type because it is less likely to misfold into inactive conformers. CONCLUSIONS: The evolution of genotypes that are more likely to exhibit a particular phenotype is an epiphenomenon usually ascribed only to complex living systems. We show that this can occur at the molecular level, demonstrating that in vitro systems may have more life-like characteristics than previously thought, and providing additional support for an RNA world.

Non-NASA Center↗

DOE OSTI2022

Registration of the sorghum carbon–partitioning nested association mapping (CP–NAM) population

The sorghum [ Sorghum bicolor (L.) Moench] carbon-partitioning nested association mapping (CP_NAM) (Reg. no. MP-4, NSL 542189 MAP) population was developed at Clemson University, SC, using 11 diverse, male founder accessions, each crossed with a recurrent female parent ‘Grassl’. The male parents represent all five major botanical races and the four major agronomic types: cellulosic (5), sweet (3), grain (2) and forage (1). A set of 11 recombinant inbred line (RIL) families CP_NAM01 to CP_NAM011 were maintained, which consisted of 2,484 (F 6 ) individuals. Each RIL family contained a minimum of 193 individuals (CP_NAM01) and a maximum of 287 individuals (CP_NAM06). For the development of this population, the founder lines were judiciously selected from the sorghum Bioenergy Association Panel based on carbon-partitioning phenotypes that make this population an ideal genetic resource for dissecting a wide range of agronomic and compositional traits for basic and applied research. The founder accessions of the CP_NAM were phenotypically characterized for various traits, including agronomic, biomass and related components, and additional compositional components. Each of the 11 F 6 RIL families of the CP_NAM were genotyped using genotyping-by-sequencing analysis, and 144,087 single nucleotide polymorphisms were generated for each individual. Genotypic information along with phenotypic data were used for the characterization of this population and to explore the range of phenotypes that permits the understanding of carbon-partitioning dynamics. This population is a unique resource for researchers to study a wide range of contrasting carbon-partitioning characteristics in sorghum to understand the genetic architecture underlying whole-plant carbon partitioning and allocation.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2022

Design and demonstration of a low‐field magnetic resonance imaging rhizotron for in‐field imaging of energy sorghum roots

Abstract Root phenotyping provides critical information to plant breeders for developing varieties with improved drought tolerance, greater root biomass, and greater nutrient use efficiency. Phenotyping roots in the natural environment is important for understanding the effect of the soil environment on root genotypic expressions. The goal of this work was to design and test a field‐scale mobile low‐field magnetic resonance imaging (LF‐MRI) Rhizotron that produces actionable root phenotyping data. We demonstrated this novel technology for root visualization and quantification using a LF‐MRI Rhizotron operating at 47 mT with two soil types. The LF‐MRI Rhizotron weights 453 kg, with a height of 90 cm, a diameter of 28 cm and an imaging field of view of 28 cm × 28 cm. The unit was operated in a Belk clay (Entic Hapluderts) and Weswood silt loam (Udifluventic Halustepts) generating 2‐D and 3‐D image data sets. The 2‐D image data had a collection time of 16.5 min per image at an image resolution of 2.2 mm per pixel. The 3‐D data had a collection time of 13 h per image with a 2.2 × 2.2 × 2.2 mm voxel resolution. Low‐field magnetic resonance imaging worked well for visualizing roots in moderate to high clay soils, demonstrating the potential for this technology; however, the broad application of this platform is hampered due to the prohibitively long scanning time to obtain 3‐D images. By increasing the field strength, and therefore the signal‐to‐noise ratio, faster scan times can enable a more useful system for root phenotyping.

Bagnall, G. Cody↗

DOE OSTI2020

Genetic control of root anatomical plasticity in maize

Root anatomical phenes have important roles in soil resource capture and plant performance; however, their phenotypic plasticity and genetic architecture is poorly understood. We hypothesized that (a) the responses of root anatomical phenes to water deficit (stress plasticity) and different environmental conditions (environmental plasticity) are genetically controlled and (b) stress and environmental plasticity are associated with different genetic loci than those controlling the expression of phenes under water-stress and well-watered conditions. Root anatomy was phenotyped in a large maize (Zea mays L.) association panel in the field with and without water deficit stress in Arizona and without water deficit stress in South Africa. Anatomical phenes displayed stress and environmental plasticity; many phenotypic responses to water deficit were adaptive, and the magnitude of response varied by genotype. We identified 57 candidate genes associated with stress and environmental plasticity and 64 candidate genes associated with phenes under well-watered and water-stress conditions in Arizona and under well-watered conditions in South Africa. Four candidate genes co-localized between plasticity groups or for phenes expressed under each condition. The genetic architecture of phenotypic plasticity is highly quantitative, and many distinct genes control plasticity in response to water deficit and different environments, which poses a challenge for breeding programs.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Assembly and comparative genome analysis of a Patagonian Aureobasidium pullulans isolate reveals unexpected intraspecific variation

Aureobasidium pullulans is a yeast-like fungus with remarkable phenotypic plasticity widely studied for its importance for the pharmaceutical and food industries. So far, genomic studies with strains from all over the world suggest they constitute a genetically unstructured population, with no association by habitat. However, the mechanisms by which this genome supports so many phenotypic permutations are still poorly understood. Recent works have shown the importance of sequencing yeast genomes from extreme environments to increase the repertoire of phenotypic diversity of unconventional yeasts. In this study, we present the genomic draft of A. pullulans strain from a Patagonian yeast diversity hotspot, re-evaluate its taxonomic classification based on taxogenomic approaches, and annotate its genome with high-depth transcriptomic data. Here, our analysis suggests this isolate could be considered a novel variant at an early stage of the speciation process. The discovery of divergent strains in a genomically homogeneous group, such as A. pullulans, can be valuable in understanding the evolution of the species. The identification and characterization of new variants will not only allow finding unique traits of biotechnological importance, but also optimize the choice of strains whose phenotypes will be characterized, providing new elements to explore questions about plasticity and adaptation.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2020

Stress-tolerant non-conventional microbes enable next-generation chemical biosynthesis

Microbial chemical production is a rapidly growing industry, with much of the growth fueled by advances in synthetic biology. New approaches have enabled rapid strain engineering for the production of various compounds; however, translation to industry is often problematic because native phenotypes of model hosts prevent the design of new low-cost bioprocesses. Here, in this work, we argue for a new approach that leverages the native stress-tolerant phenotypes of non-conventional microbes that directly address design challenges from the outset. Growth at high temperature, high salt and solvent concentrations, and low pH can enable cost savings by reducing the energy required for product separation, bioreactor cooling, and maintaining sterile conditions. These phenotypes have the added benefit of allowing for the use of low-cost sugar and water resources. Non-conventional hosts are needed because these phenotypes are polygenic and thus far have proven difficult to recapitulate in the common hosts Escherichia coli and Saccharomyces cerevisiae.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗

DOE OSTI2024

Stochastic journeys of cell progenies through compartments and the role of self-renewal, symmetric and asymmetric division

Abstract Division and differentiation events by which cell populations with specific functions are generated often take place as part of a developmental programme, which can be represented by a sequence of compartments. A compartment is the set of cells with common characteristics; sharing, for instance, a spatial location or a phenotype. Differentiation events are transitions from one compartment to the next. Cells may also die or divide. We consider three different types of division events: (i) where both daughter cells inherit the mother’s phenotype (self-renewal), (ii) where only one of the daughters changes phenotype (asymmetric division), and (iii) where both daughters change phenotype (symmetric division). The self-renewal probability in each compartment determines whether the progeny of a single cell, moving through the sequence of compartments, is finite or grows without bound. We analyse the progeny stochastic dynamics with probability generating functions. In the case of self-renewal, by following one of the daughters after any division event, we may construct lifelines containing only one cell at any time. We analyse the number of divisions along such lines, and the compartment where lines terminate with a death event. Analysis and numerical simulations are applied to a five-compartment model of the gradual differentiation of hematopoietic stem cells and to a model of thymocyte development: from pre-double positive to single positive (SP) cells with a bifurcation to either SP4 or SP8 in the last compartment of the sequence.

Science & Technology - Other Topics↗

DOE OSTI2024

Cryo-EM confirms a common fibril fold in the heart of four patients with ATTRwt amyloidosis

ATTR amyloidosis results from the conversion of transthyretin into amyloid fibrils that deposit in tissues causing organ failure and death. This conversion is facilitated by mutations in ATTRv amyloidosis, or aging in ATTRwt amyloidosis. ATTRv amyloidosis exhibits extreme phenotypic variability, whereas ATTRwt amyloidosis presentation is consistent and predictable. Previously, we found unique structural variabilities in cardiac amyloid fibrils from polyneuropathic ATTRv-I84S patients. In contrast, cardiac fibrils from five genotypically different patients with cardiomyopathy or mixed phenotypes are structurally homogeneous. To understand fibril structure’s impact on phenotype, it is necessary to study the fibrils from multiple patients sharing genotype and phenotype. Here we show the cryo-electron microscopy structures of fibrils extracted from four cardiomyopathic ATTRwt amyloidosis patients. Our study confirms that they share identical conformations with minimal structural variability, consistent with their homogenous clinical presentation. Our study contributes to the understanding of ATTR amyloidosis biopathology and calls for further studies.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

Transcription factor bHLH121 regulates root cortical aerenchyma formation in maize

Root anatomical phenotypes present a promising yet underexploited avenue to deliver major improvements in yield and climate resilience of crops by improving water and nutrient uptake. For instance, the formation of root cortical aerenchyma (RCA) significantly increases soil exploration and resource capture by reducing the metabolic costs of root tissue. A key bottleneck in studying such phenotypes has been the lack of robust high-throughput anatomical phenotyping platforms. We exploited a phenotyping approach based on laser ablation tomography, termed Anatomics , to quantify variation in RCA formation of 436 diverse maize lines in the field. Results revealed a significant and heritable variation for RCA formation. Genome-wide association studies identified a single-nucleotide polymorphism mapping to a root cortex-expressed gene-encoding transcription factor bHLH121. Functional studies identified that the bHLH121 Mu transposon mutant line and CRISPR/Cas9 loss-of-function mutant line showed reduced RCA formation, whereas an overexpression line exhibited significantly greater RCA formation when compared to the wild-type line. Characterization of these lines under suboptimal water and nitrogen availability in multiple soil environments revealed that bHLH121 is required for RCA formation developmentally as well as under studied abiotic stress. Overall functional validation of the bHLH121 gene’s importance in RCA formation provides a functional marker to select varieties with improved soil exploration and thus yield under suboptimal conditions.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2021

Genetic characterization of a Sorghum bicolor multiparent mapping population emphasizing carbon-partitioning dynamics

Sorghum bicolor, a photosynthetically efficient C4 grass, represents an important source of grain, forage, fermentable sugars, and cellulosic fibers that can be utilized in myriad applications ranging from bioenergy to bioindustrial feedstocks. Sorghum’s efficient fixation of carbon per unit time per unit area per unit input has led to its classification as a preferred biomass crop highlighted by its designation as an advanced biofuel by the U.S. Department of Energy. Due to its extensive genetic diversity and worldwide colonization, sorghum has considerable diversity for a range of phenotypes influencing productivity, composition, and sink/source dynamics. To dissect the genetic basis of these key traits, we present a sorghum carbon-partitioning nested association mapping (NAM) population generated by crossing 11 diverse founder lines with Grassl as the single recurrent female. By exploiting existing variation among cellulosic, forage, sweet, and grain sorghum carbon partitioning regimes, the sorghum carbon-partitioning NAM population will allow the identification of important biomass-associated traits, elucidate the genetic architecture underlying carbon partitioning and improve our understanding of the genetic determinants affecting unique phenotypes within Poaceae. We contrast this NAM population with an existing grain population generated using Tx430 as the recurrent female. Genotypic data are assessed for quality by examining variant density, nucleotide diversity, linkage decay, and are validated using pericarp and testa phenotypes to map known genes affecting these phenotypes. We release the 11-family NAM population along with corresponding genomic data for use in genetic, genomic, and agronomic studies with a focus on carbon-partitioning regimes.

multiparental populations↗

DOE OSTI2021

Integrating crop growth models with remote sensing for predicting biomass yield of sorghum

Abstract Plant phenotypes are often descriptive, rather than predictive of crop performance. As a result, extensive testing is required in plant breeding programmes to develop varieties aimed at performance in the target environments. Crop models can improve this testing regime by providing a predictive framework to (i) augment field phenotyping data and derive hard-to-measure phenotypes and (ii) estimate performance across geographical regions using historical weather data. The goal of this study was to parameterize the Agricultural Production Systems sIMulator (APSIM) crop growth models with remote-sensing and ground-reference data to predict variation in phenology and yield-related traits in 18 commercial grain and biomass sorghum hybrids. Genotype parameters for each hybrid were estimated using remote-sensing measurements combined with manual phenotyping in West Lafayette, IN, in 2018. The models were validated in hybrid performance trials in two additional seasons at that site and against yield trials conducted in Bushland, TX, between 2001 and 2018. These trials demonstrated that (i) maximum plant height, final dry biomass and radiation use efficiency (RUE) of photoperiod-sensitive and -insensitive forage sorghum hybrids tended to be higher than observed in grain sorghum, (ii) photoperiod-sensitive sorghum hybrids exhibited greater biomass production in longer growing environments and (iii) the parameterized and validated models perform well in above-ground biomass simulations across years and locations. Crop growth models that integrate remote-sensing data offer an efficient approach to parameterize larger plant breeding populations.

Yang, Kai-Wei↗

DOE OSTI2023

Promoter deletion in the soybean Compact mutant leads to overexpression of a gene with homology to the C 20 -gibberellin 2-oxidase family

Height is a critical component of plant architecture, significantly affecting crop yield. The genetic basis of this trait in soybean remains unclear. In this study, we report the characterization of the Compact mutant of soybean, which has short internodes. The candidate gene was mapped to chromosome 17, and the interval containing the causative mutation was further delineated using biparental mapping. Whole-genome sequencing of the mutant revealed an 8.7 kb deletion in the promoter of the Glyma.17g145200 gene, which encodes a member of the class III gibberellin (GA) 2-oxidases. The mutation has a dominant effect, likely via increased expression of the GA 2-oxidase transcript observed in green tissue, as a result of the deletion in the promoter of Glyma.17g145200. We further demonstrate that levels of GA precursors are altered in the Compact mutant, supporting a role in GA metabolism, and that the mutant phenotype can be rescued with exogenous GA3. We also determined that overexpression of Glyma.17g145200 in Arabidopsis results in dwarfed plants. Thus, gain of promoter activity in the Compact mutant leads to a short internode phenotype in soybean through altered metabolism of gibberellin precursors. Furthermore, these results provide an example of how structural variation can control an important crop trait and a role for Glyma.17g145200 in soybean architecture, with potential implications for increasing crop yield.

59 BASIC BIOLOGICAL SCIENCES↗

DOE OSTI2023

CRISPR/Cas9 mutants delineate roles of Populus FT and TFL1/CEN/BFT family members in growth, dormancy release and flowering

Abstract Vegetative and reproductive phase change and phenology are economically and ecologically important traits. Trees typically require several years of growth before flowering and, once mature, seasonal control of the transition to flowering and flower development is necessary to maintain vegetative meristems and for reproductive success. Members of two related gene subfamilies, FLOWERING LOCUST (FT) and TERMINAL FLOWER1 (TFL1)/CENTRORADIALIS (CEN)/BROTHER OF FT AND TFL1 (BFT), have antagonistic roles in flowering in diverse species and roles in vegetative phenology in trees, but many details of their functions in trees have yet to be resolved. Here, we used CRISPR/Cas9 to generate single and double mutants involving the five Populus FT and TFL1/CEN/BFT genes. The ft1 mutants exhibited wild-type-like phenotypes in long days and short days, but after chilling, to release dormancy, they showed delayed bud flush and GA3 could compensate for the ft1 mutation. After rooting and generating some phytomers in tissue culture, both cen1 and cen1ft1 mutants produced terminal as well as axillary flowers, indicating that the cen1 flowering phenotype is independent of FT1. The CEN1 showed distinct circannual expression patterns in vegetative and reproductive tissues and comparison with the expression patterns of FT1 and FT2 suggests that the relative levels of CEN1 compared with FT1 and FT2 regulate multiple phases of vegetative and reproductive seasonal development.

Forestry↗

DOE OSTI2021

Topologically Associating Domain Boundaries are Commonly Required for Normal Genome Function

Topologically associating domain (TAD) boundaries are thought to partition the genome into distinct regulatory territories. Anecdotal evidence suggests that their disruption may interfere with normal gene expression and cause disease phenotype, but the overall extent to which this occurs remains unknown. Here we show that TAD boundary deletions commonly disrupt normal genome function in vivo . We used CRISPR genome editing in mice to individually delete eight TAD boundaries (11-80kb in size) from the genome in mice. All deletions examined resulted in at least one detectable molecular or organismal phenotype, which included altered chromatin interactions or gene expression, reduced viability, and anatomical phenotypes. For 5 of 8 (62%) loci examined, boundary deletions were associated with increased embryonic lethality or other developmental phenotypes. For example, a TAD boundary deletion near Smad3/Smad6 caused complete embryonic lethality, while a deletion near Tbx5/Lhx5 resulted in a severe lung malformation. Our findings demonstrate the importance of TAD boundary sequences for in vivo genome function and suggest that noncoding deletions affecting TAD boundaries should be carefully considered for potential pathogenicity in clinical genetics screening.

Rajderkar, Sudha↗

DOE OSTI2025

Host-specific adaptation in Fusarium oxysporum correlates with distinct accessory chromosome content in human and plant pathogenic strains

ABSTRACT Fusarium oxysporumis a cross-kingdom pathogen. While some strains cause disseminated fusariosis and blinding corneal infections in humans, others are responsible for devastating vascular wilt diseases in plants. To better understand the distinct adaptations ofF. oxysporumto animal or plant hosts, we conducted a comparative phenotypic and genetic analysis of two strains: MRL8996 (isolated from a keratitis patient) and Fol4287 (isolated from a wilted tomato [Solanum lycopersicum]). Infection of mouse corneas and tomato plants revealed that, while both strains cause symptoms in both hosts, MRL8996 caused more severe corneal disease in mice, whereas Fol4287 induced more pronounced wilting symptoms in tomato plants.In vitroassays using abiotic stress treatments revealed that the human pathogen MRL8996 was better adapted to elevated temperatures, whereas the plant pathogen Fol4287 was more tolerant to osmotic and cell wall stresses. Both strains displayed broad resistance to antifungal treatment, with MRL8996 exhibiting the paradoxical effect of increased tolerance to higher concentrations of the antifungal caspofungin. We identified a set of accessory chromosomes (ACs) that encode genes with different functions and have distinct transposon profiles between MRL8996 and Fol4287. Interestingly, ACs from both genomes also encode proteins with shared functions, such as chromatin remodeling and post-translational protein modifications. Our phenotypic assays and comparative genomics analyses lay the foundation for future studies correlating genotypes with phenotype and for developing targeted antifungals for agricultural and clinical uses. IMPORTANCE Fusarium oxysporumis a cross-kingdom fungal pathogen that infects both plants and animals. In addition to causing many devastating wilt diseases, this group of organisms was recently recognized by the World Health Organization as a high-priority threat to human health. Climate change has increased the risk ofFusariuminfections, asFusariumstrains are highly adaptable to changing environments. Deciphering fungal adaptation mechanisms is crucial to developing appropriate control strategies. We performed a comparative analysis ofFusariumstrains using an animal (mouse) and plant (tomato) host andin vitroconditions that mimic abiotic stress. We also performed comparative genomics analyses to highlight the genetic differences between human and plant pathogens and correlate their phenotypic and genotypic variations. We uncovered important functional hubs shared by plant and human pathogens, such as chromatin modification, transcriptional regulation, and signal transduction, which could be used to identify novel antifungal targets.

Microbiology↗