Biology subjects

Rodrigues, F.

Publications and source records attributed to Rodrigues, F..

15 recordsLinked to original sources

bioRxiv2025

From smartphones to satellites: Uniting crowdsourced biodiversity monitoring and Earth observation to fill the gaps in global plant trait mapping

Plant functional traits are fundamental to ecosystem dynamics and Earth system processes, but their global characterization is limited by the availability of field surveys and trait measurements. Recent expansions in biodiversity data aggregation, including large collections of vegetation surveys, citizen science observations, and trait measurements, offer new opportunities to overcome these constraints. Here we demonstrate that combining these diverse data sources with high-resolution Earth observation data enables accurate modeling of key plant traits at up to 1 km resolution. Our approach achieves high predictive power, reaching correlations up to 0.63 (15 of 31 traits exceeding 0.50) and improved spatial transferability, effectively bridging gaps in under-sampled regions. By capturing a broad range of traits with high spatial coverage, these maps can enhance our understanding of plant community properties and ecosystem functioning globally, and can serve as useful tools in modeling global biogeochemical processes and informing worldwide conservation efforts. Ultimately, our framework highlights the power and necessity of crowdsourced biodiversity data in high-resolution plant trait modeling. We anticipate that advancements in biodiversity data collection and remote sensing capabilities will further refine global trait mapping, fostering a dynamic trait-based understanding of the biosphere.

ecology↗

bioRxiv2024

Type I interferons induced upon respiratory viral infection impair lung metastatic initiation

Invasive breast cancer accounts for 7% of all cancer-related deaths, with the lungs being a common site of metastases. At the same time, lower respiratory tract infections are a common cause of morbidity and mortality worldwide. Acute viral respiratory infections induce transitional changes in the lung; however, the impact of these changes on metastasis initiation and cancer progression remains unclear. Using primary murine MMTV-PyMT breast cancer cells in an experimental lung metastasis model, we show that changes induced by respiratory syncytial virus (RSV) infection impair tumor cell seeding and early establishment in the lung, resulting in lower number of metastatic nodules. Furthermore, we demonstrate that this reduction of metastases is due to alterations in the lung environment mediated by type I interferons (IFNs) that are produced in response to RSV infection. Consistent with that notion, intranasal administration of recombinant IFN- recapitulates the anti-tumor effect of RSV infection. Type I IFNs change the lung cellular composition and induce an Interferon Stimulated Gene (ISG) driven response, creating an alveolar environment that is less supportive of tumor cell growth. Indeed, epithelial cells from mice infected with RSV or intranasally exposed to IFN-, are less supportive of tumor cell growth ex vivo. Altogether, our results suggest that type I IFNs induced by infection with some respiratory viruses perturb the lungs and consequently interfere with the ability of tumor cells to successfully initiate metastatic colonization. SignificanceWomen diagnosed with metastatic breast cancer have a low survival rate. The lungs are a common metastatic site and are constantly exposed to viral pathogens, such as coronavirus, RSV and influenza virus. Thus, breast cancer and respiratory virus infection are likely to co-occur, but their interplay remains unclear. We show that type I interferons (IFNs), induced upon viral infection impair metastatic cancer cell seeding of mouse lungs. This is potentially via an effect of IFNs on lung epithelial cells, which become less supportive of early tumor cell proliferation. These findings indicate that viral infections and type I IFNs can alter the lung environment and impair implantation of metastatic cells, which could be explored to improve future cancer treatments.

immunology↗

bioRxiv2024

VEXAS anemia is a mosaic erythroblastopenia

VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is a recently discovered autoinflammatory disorder linked to somatic mutations in the UBA1 gene, resulting in a profound cytoplasm-restricted defect in ubiquitylation. The disease is characterized by a macrocytic anemia that remains poorly understood. To investigate the erythroid lineage in VEXAS, we conducted a comprehensive study combining in vivo assessments of patients mature red cells and marrow erythroblasts, alongside in vitro base-editing models of erythropoiesis. Here we show that mature red cells do not exhibit ubiquitylation defects, and patient-derived bone marrow erythroblasts lack UBA1 mutations beyond the basophilic stage of erythroid differentiation. In vitro base editing of UBA1 variants in CD34+ primary cells resulted in high mortality during early erythroid differentiation, but not during monocytic differentiation. Edited erythroid precursors displayed TP53 overexpression linked to defective ubiquitylation and anomalies in ribosome biogenesis, reminiscent of Diamond-Blackfan anemia. We propose that VEXAS-associated anemia should be considered as a mosaic erythroblastopenia, where the severity of anemia is influenced by the quality and quantity of the UBA1-WT compartment. These insights may aid clinicians in tailoring treatment strategies.

cell biology↗

bioRxiv2024

Electrical stimulation of grape berries as new alternative for post-harvest infection management

Viticulture stands out as a primary agricultural sector in the EU. However, an intensive regime of chemical pesticides is used to meet production standards. Consequently, the EU has taken measures to encourage the promotion of sustainable agrochemical practices. It has recently been demonstrated that low voltage and electrical current can also successfully destroy different type of microorganisms such as bacteria and fungi. However, the application of electric current has not been much explored for preventing early stages of fresh fruit rotting. As a result, an innovative setup was developed to study the effect of an alternating current (50 mA) on grapes previously contaminated with E. coli. A visual analysis of the state of degradation of the grapes 12 days after the electrical treatment allowed us to conclude that the contaminated grapes subjected to electrical treatment (at day 1) did not show visual contamination, when compared to the contaminated grapes without electrical treatment, presenting a similar appearance to the grapes used as control. The quantitative assay also confirmed this result since on the NB agar plates it was possible to visualize a significant reduction in colonies, corresponding to 2 log10 CFU/mL, indicating that approximately 99% of the E. coli previously attached to the berry surface was eradicated. This environmentally sustainable solution aims to reduce dependence on pesticides. Still, other studies will focus on validating its effectiveness against target microorganisms and optimizing a conductive network for applying electrical stimuli to a bunch of grapes.

microbiology↗

bioRxiv2023

Evolutionary origin, population diversity, and diagnostics for a cryptic hybrid pathogen

Cryptic fungal pathogens pose significant identification and disease management challenges due to their morphological resemblance to known pathogenic species while harboring genetic and (often) infection-relevant trait differences. The cryptic fungal pathogen Aspergillus latus, an allodiploid hybrid originating from Aspergillus spinulosporus and an unknown close relative of Aspergillus quadrilineatus within section Nidulantes, remains poorly understood. The absence of accurate diagnostics for A. latus has led to misidentifications, hindering epidemiological studies and the design of effective treatment plans. We conducted an in-depth investigation of the genomes and phenotypes of 44 globally distributed isolates (41 clinical isolates and three type strains) from Aspergillus section Nidulantes. We found that 21 clinical isolates were A. latus; notably, standard methods of pathogen identification misidentified all A. latus isolates. The remaining isolates were identified as A. spinulosporus (8), A. quadrilineatus (1), or A. nidulans (11). Phylogenomic analyses shed light on the origin of A. latus, indicating one or two hybridization events gave rise to the species during the Miocene, approximately 15.4 to 8.8 million years ago. Characterizing the A. latus pangenome uncovered substantial genetic diversity within gene families and biosynthetic gene clusters. Transcriptomic analysis revealed that both parental genomes are actively expressed in nearly equal proportions and respond to environmental stimuli. Further investigation into infection-relevant chemical and physiological traits, including drug resistance profiles, growth under oxidative stress conditions, and secondary metabolite biosynthesis, highlight distinct phenotypic profiles of the hybrid A. latus compared to its parental and closely related species. Leveraging our comprehensive genomic and phenotypic analyses, we propose five genomic and phenotypic markers as diagnostics for A. latus species identification. These findings provide valuable insights into the evolutionary origin, genomic outcome, and phenotypic implications of hybridization in a cryptic fungal pathogen, thus enhancing our understanding of the underlying processes contributing to fungal pathogenesis. Furthermore, our study underscores the effectiveness of extensive genomic and phenotypic analyses as a promising approach for developing diagnostics applicable to future investigations of cryptic and emerging pathogens.

evolutionary biology↗

bioRxiv2022

Hemisynthetic derivatives of the natural alkaloid trilobine are fast-acting antimalarial compounds with sustained activity in multi-drug resistant P. falciparum isolates

Malaria eradication requires the development of new drugs to combat drug-resistant parasites. The search for new chemical scaffolds that target novel pathways of the human malaria parasite Plasmodium falciparum is of highest priority. We identified bisbenzylisoquinoline alkaloids isolated from Cocculus hirsutus. (trilobine derivatives) as active in the nanomolar range against P. falciparum blood stages. Synthesis of a library of 94 hemi-synthetic derivatives allowed us to identify compound 84 that kills multi-drug resistant clinical isolates in the nanomolar range (median IC50 ranging from 35-88nM). Efforts were made to obtain compounds with significantly improved preclinical properties. Out of those, compound 125 delays the onset of parasitemia in P. berghei infected mice and inhibits P. falciparum transmission stages in vitro (culture assays) and in vivo using membrane feeding assay in the Anopheles stephensi vector. Compound 125 also impairs P. falciparum development in sporozoite-infected hepatocytes, in the low micromolar range. Finally, we used a chemical pull-down strategy to identify potential protein targets of this chemical family. Mass spectrometry analysis identified the parasite interactome with trilobine derivatives, identifying protein partners belonging to metabolic pathways that have not been previously targeted by antimalarial drugs or implicated in drug-resistance mechanisms.

pathology↗

bioRxiv2021

Aspergillus fumigatus acetate utilisation impacts virulence traits and pathogenicity

Aspergillus fumigatus is a major opportunistic fungal pathogen of immunocompromised and immunocompetent hosts. To successfully establish an infection, A. fumigatus needs to use host carbon sources, such as acetate, present in the body fluids and peripheral tissues. However, utilisation of acetate as a carbon source by fungi in the context of infection has not been investigated. This work shows that acetate is metabolised via different pathways in A. fumigatus and that acetate utilisation is under the regulatory control of a transcription factor (TF), FacB. A. fumigatus acetate utilisation is subject to carbon catabolite repression (CCR), although this is only partially dependent on the TF and main regulator of CCR CreA. The available extracellular carbon source, in this case glucose and acetate, significantly affected A. fumigatus virulence traits such as secondary metabolite secretion and cell wall composition, with the latter having consequences for resistance to oxidative stress, to anti-fungal drugs and to human neutrophil-mediated killing. Furthermore, deletion of facB significantly impaired the in vivo virulence of A. fumigatus in both insect and mammalian models of invasive aspergillosis. This is the first report on acetate utilisation in A. fumigatus and this work further highlights the importance of available host-specific carbon sources in shaping fungal virulence traits and subsequent disease outcome, and a potential target for the development of anti-fungal strategies. ImportanceAspergillus fumigatus is an opportunistic fungal pathogen in humans. During infection, A. fumigatus is predicted to use host carbon sources, such as acetate, present in body fluids and peripheral tissues, to sustain growth and promote colonisation and invasion. This work shows that A. fumigatus metabolises acetate via different pathways, a process that is dependent on the transcription factor FacB. Furthermore, the type and concentration of the extracellular available carbon source were determined to shape A. fumigatus virulence determinants such as secondary metabolite secretion and cell wall composition. Subsequently, interactions with immune cells are altered in a carbon source-specific manner. FacB is required for A. fumigatus in vivo virulence in both insect and mammalian models of invasive aspergillosis. This is the first report that characterises acetate utilisation in A. fumigatus and highlights the importance of available host-specific carbon sources in shaping virulence traits and potentially subsequent disease outcome.

microbiology↗

bioRxiv2020

Metagenome-assembled genomes from Monte Cristo Cave (Diamantina, Brazil) reveal prokaryotic lineages as functional models for life on Mars

Although several studies have explored microbial communities in different terrestrial subsurface ecosystems, little is known about the diversity of their metabolic processes and survival strategies. The advance of bioinformatic tools is allowing the description of novel and not-yet cultivated microbial lineages in different ecosystems, due to the genome reconstruction approach from metagenomic data. The recovery of genomes has the potential of revealing novel lifestyles, metabolic processes and ecological roles of microorganisms, mainly in ecosystems that are largely unknown, and in which cultivation could be not viable. In this study, through shotgun metagenomic data, it was possible to reconstruct several genomes of cultivated and not-yet cultivated prokaryotic lineages from a quartzite cave, located in Minas Gerais state, Brazil, which showed to possess a high diversity of genes involved with different biogeochemical cycles, including reductive and oxidative pathways related to carbon, sulfur, nitrogen and iron. Tree genomes were selected, assigned as Truepera sp., Ca. Methylomirabilis sp. and Ca. Koribacter sp. based on their lifestyles (radiation resistance, anaerobic methane oxidation and potential iron oxidation) for pangenomic analysis, which exhibited genes involved with different DNA repair strategies, starvation and stress response. Since these groups have few reference genomes deposited in databases, our study adds important genomic information about these lineages. The combination of techniques applied in this study allowed us to unveil the potential relationships between microbial genomes and their ecological processes with the cave mineralogy, as well as to discuss their implications for the search for extant lifeforms outside our planet, in silica- and iron-rich environments, especially on Mars.

microbiology↗

bioRxiv2020

Cerebrospinal fluid endo-lysosomal proteins as potential biomarkers for Huntingtons disease.

Molecular markers derived from cerebrospinal fluid (CSF) represent an accessible means of exploring the pathobiology of Huntingtons disease (HD) in vivo. The endo-lysosomal/autophagy system is dysfunctional in HD, potentially contributing to disease pathogenesis and representing a potential target for therapeutic intervention. Several endo-lysosomal proteins have shown promise as biomarkers in other neurodegenerative diseases; however, they have yet to be fully explored in HD. We performed parallel reaction monitoring mass spectrometry analysis (PRM-MS) of multiple endo-lysosomal proteins in the CSF of 60 HD mutation carriers and 20 healthy controls. Using generalised linear models controlling for age and CAG, none of the 18 proteins measured displayed significant differences in concentration between HD patients and controls. This was affirmed by principal component analysis, in which no significant difference across disease stage was found in any of the three components representing lysosomal hydrolases, binding/transfer proteins and innate immune system/peripheral proteins. However, several proteins were associated with measures of disease severity and cognition: most notably amyloid precursor protein, which displayed strong correlations with composite Unified Huntingtons Disease Rating Scale, UHDRS Total Functional Capacity, UHDRS Total Motor Score, Symbol Digit Modalities Test and Stroop Word Reading. We conclude that although endo-lysosomal proteins are unlikely to have value as disease state CSF biomarkers for Huntingtons disease, several proteins demonstrate associations with clinical severity, thus warranting further, targeted exploration and validation in larger, longitudinal samples.

neuroscience↗

bioRxiv2020

Functional characterization of clinical isolates of the opportunistic fungal pathogen Aspergillus nidulans

Aspergillus nidulans is an opportunistic fungal pathogen in patients with immunodeficiency and virulence of A. nidulans isolates has mainly been studied in the context of the chronic granulomatous disease (CGD), with characterization of clinical isolates obtained from non-CGD patients remaining elusive. This study therefore carried out a detailed biological characterization of two A. nidulans clinical isolates (CIs), obtained from a patient with breast carcinoma and pneumonia and from a patient with cystic fibrosis that underwent lung transplantation, and compared them to the reference, non-clinical A4 strain. Both CIs presented increased growth in comparison to the reference strain in the presence of physiologically-relevant carbon sources. Metabolomic analyses showed that the three strains are metabolically very different from each other in these carbon sources. Furthermore, the CIs were highly susceptible to cell wall perturbing agents but not to other physiologically-relevant stresses. Genome analyses identified several frame-shift variants in genes encoding cell wall integrity (CWI) signalling components. Significant differences in CWI signalling were confirmed by western blotting among the three strains. In vivo virulence studies using several different models revealed that strain MO80069 had significantly higher virulence in hosts with impaired neutrophil function when compared to the other strains. In summary, this study presents detailed biological characterization of two A. nidulans sensu stricto clinical isolates. Just like in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits. Further studies are required to fully characterize A. nidulans strain-specific virulence traits and pathogenicity. ImportanceImmunocompromised patients are susceptible to infections with opportunistic filamentous fungi from the genus Aspergillus. Although A. fumigatus is the main etiological agent of Aspergillus spp.-related infections, other species, such as A. nidulans are prevalent in a condition-specific manner. A. nidulans is a predominant infective agent in patients suffering from chronic granulomatous disease (CGD). A. nidulans isolates have mainly been studied in the context of CGD, although infection with A. nidulans also occurs in non-CGD patients. This study carried out a detailed biological characterization of two non-CGD A. nidulans clinical isolates and compared it to a reference strain. Phenotypic, metabolomic and genomic analyses highlight fundamental differences in carbon source utilization, stress responses and maintenance of cell wall integrity among the strains. One clinical strain had increased virulence in models with impaired neutrophil function. Just as in A. fumigatus, strain heterogeneity exists in A. nidulans clinical strains that can define virulence traits.

microbiology↗

bioRxiv2019

Genome-wide association analysis for resistance to infectious pancreatic necrosis virus identifies candidate genes involved in viral replication and immune response in rainbow trout (Oncorhynchus mykiss)

Infectious pancreatic necrosis (IPN) is a viral disease with considerable negative impact on the rainbow trout (Oncorhynchus mykiss) aquaculture industry. The aim of the present work was to detect genomic regions that explain resistance to infectious pancreatic necrosis virus (IPNV) in rainbow trout. A total of 2,278 fish from 58 full-sib families were challenged with IPNV. Of the challenged fish, 768 individuals were genotyped (488 resistant and 280 susceptible), using a 57K single nucleotide polymorphisms (SNPs) panel Axiom(R), Affymetrix(R). A genome-wide association study (GWAS) was performed using the phenotypes time to death (TD) and binary survival (BS), along with the genotypes of the challenged fish using a Bayesian model (Bayes C). Heritabilities for resistance to IPNV estimated using pedigree information, were 0.39 and 0.32 for TD and BS, respectively. Heritabilities for resistance to IPNV estimated using genomic information, were 0.50 and 0.54 for TD and BS, respectively. The Bayesian GWAS detected a SNP located on chromosome 5 explaining 18% of the genetic variance for TD. A SNP located on chromosome 23 was detected explaining 9% of the genetic variance for BS. The proximity of Sentrin-specific protease 5 (SENP5) to a significant SNP makes it a candidate gene for resistance against IPNV. However, the moderate-low proportion of variance explained by the detected marker leads to the conclusion that the incorporation of all genomic information, through genomic selection, would be the most appropriate approach to accelerate genetic progress for the improvement of resistance against IPNV in rainbow trout.

genomics↗

bioRxiv2019

Paracoccin overexpression in Paracoccidioides brasiliensis reveals the influence of chitin hydrolysis on fungal virulence and host immune response

Paracoccidioides brasiliensis and P. lutzii, etiological agents of paracoccidioidomycosis (PCM), develop as mycelia at 25-30 {degrees}C and as yeast at 35-37 {degrees}C. Only a few Paracoccidioides spp. proteins are well characterized. Thus, we studied paracoccin (PCN) from P. brasiliensis, its role in the fungus biology, and its relationship with the host innate immune cells. Cloning and heterologous expression analysis revealed its lectin, enzymatic, and immunomodulatory properties. Recently, we employed a system based on Agrobacterium tumefaciens-mediated transformation to manipulate P. brasiliensis yeast genes to obtain clones knocked-down for PCN, which after all, are unable to transit from yeast to mycelium forms, causing a mild pulmonary disease. Herein, we generate P. brasiliensis overexpressing PCN (ov-PCN). To date, it was not explored the overexpressing of endogenous components in Paracoccidioides spp. Therefore, we investigate the role of PCN in fungal biology and pathogenesis. Augmented levels of PCN mRNA and protein, and N-acetylglucosaminidase activity confirmed PCN overexpression in ov-PCN of P. brasiliensis yeasts. Interestingly, PCN overexpression did not affect the yeasts growth or viability and favored cell separation. The ov-PCN clones transitioned faster to the mycelium form than the wt-PCN yeasts. Concerning infection, while most of mice infected with the wt-yeasts (90%) survive at least until the 70th day, all mice infected with ov-PCN yeasts were already died at the 35th day post-infection. In vitro assays showed that ov-PCN were more susceptible to phagocytosis by macrophages. Finally, it was verified that the chitin particles isolated from the ov-PCN cells were smaller than those obtained from the wt-PCN yeasts. Macrophages stimulated with the chitin isolated from ov-PCN produce IL-10, whereas the particles with a wider size range harvested from wt-PCN yeasts induced TNF- and IL-1{beta} secretion. The anti-inflammatory microenvironment from macrophage stimulation with small chitin particles hampers the development of a protective immune response against the fungus. We postulated that the high grade of chitin cleavage, as the results of augmented PCN expression, favors pathogenesis following P. brasiliensis infection. Thus, PCN is a relevant virulence fungal factor.\n\nAUTHOR SUMMARYParacoccidioides spp. are pathogenic fungi that cause paracoccidioidomycosis (PCM) in humans, the main deep mycosis of Latin America. Recently, by knocking down the paracoccin gene, our group showed that this lectin is necessary for the morphological transition from yeast to hyphae, and that this decrease results in low P. brasiliensis virulence. Here, after overexpress PCN, we revealed the importance of the yeast chitin hydrolysis to the host response. Infection of mice with ov-PCN yeasts causes severe lung disease compared to moderate disease caused by wt-PCN yeasts. The release of smaller chitin particles was as a result of an accelerated chitin hydrolysis provided by ov-PCN yeasts. Interestingly, these smallest chitin particles are able to modulate host response by increasing IL-10 in the meantime that decrease TNF- secretion, thus hampering Th1 immune response that is crucial in the fight against this fungi. These findings represent a significant advance in the knowledge about the role of PCN chitinase in P. brasiliensis.

microbiology↗

bioRxiv2018

Insights on the assembly rules of a continent-wide multilayer network

Introductory paragraphHow are ecological systems assembled? Here, we aim to contribute to answering this question by harnessing the framework of a novel integrative hypothesis. We shed light on the assembly rules of a multilayer network formed by frugivory and nectarivory interactions between bats and plants in the Neotropics. Our results suggest that, at a large scale, phylogenetic trade-offs separate species into different layers and modules. At an intermediate scale, the modules are also shaped by geographic trade-offs. And at a small scale, the network shifts to a nested structure within its modules, probably as a consequence of resource breadth processes. Finally, once the topology of the network is shaped, morphological traits related to consuming fruits or nectar determine which species are central or peripheral. Our results help understand how different processes contribute to the assemblage of ecological systems at different scales, resulting in a compound topology.

ecology↗

bioRxiv2018

Survival and ice nucleation activity of Pseudomonas syringae strains exposed to simulated high-altitude atmospheric conditions

The epiphytic bacterium Pseudomonas syringae produces the most efficient and well-studied biological ice nuclei (IN) known. Bioaerosols containing these cells have been proposed to influence cloud glaciation, an important process in the initiation of precipitation. The presence of this species has been reported on rain, snow, and cloud water samples, but how these organisms can survive the harsh conditions present on the high atmosphere still remains to be better understood. In this study, the impact caused by this type of environment on P. syringae was assayed by measuring their viability and IN activity. Two strains, of the pathovars syringae and garcae, were compared to Escherichia coli. While UV-C radiation effectively inactivated these cells, the Pseudomonas were much more tolerant to UV-B. The P. syringae strains were also more resistant to \"environmental\" UV radiation from a solar simulator, composed of UV-A and UV-B. The response of their IN after long exposures to this radiation varied: only one strain suffered a relatively small 10-fold reduction in IN activity at -5 {degrees}C. Desiccation at different relative humidity values also affected the IN, but some activity at -5 {degrees}C was still maintained for all tests. The pathovar garcae tended to be more resistant to the stress treatments than the pathovar syringae, particularly to desiccation, though its IN were found to be more sensitive. Compared to E. coli, the P. syringae strains seemed relatively better adapted to survival under conditions present on the atmosphere at high altitudes.\n\nIMPORTANCEThe plant-associated bacterium Pseudomonas syringae produces on its outer membrane highly efficient ice nuclei which are able to induce the freezing of supercooled water. This ability has been linked to increased frost damaged on colonized leaves and also to the formation of ice in clouds, an important process leading to precipitation. P. syringae has been found on rain, snow, and cloud water samples, confirming its presence on the atmosphere. This study aimed to assess the survival of these cells and the maintenance of their ice nucleation activity under stressing conditions present in high altitudes: ultraviolet radiation and desiccation. P. syringae strains were shown to at least partially tolerate these factors, and their most efficient ice nuclei, while affected, could still be detected after all experiments.

microbiology↗

bioRxiv2017

Drivers of genetic diversity in secondary metabolic gene clusters in a fungal population

Filamentous fungi produce a diverse array of secondary metabolites (SMs) critical for defense, virulence, and communication. The metabolic pathways that produce SMs are found in contiguous gene clusters in fungal genomes, an atypical arrangement for metabolic pathways in other eukaryotes. Comparative studies of filamentous fungal species have shown that SM gene clusters are often either highly divergent or uniquely present in one or a handful of species, hampering efforts to determine the genetic basis and evolutionary drivers of SM gene cluster divergence. Here we examined SM variation in 66 cosmopolitan strains of a single species, the opportunistic human pathogen Aspergillus fumigatus. Investigation of genome-wide within-species variation revealed five general types of variation in SM gene clusters: non-functional gene polymorphisms, gene gain and loss polymorphisms, whole cluster gain and loss polymorphisms, allelic polymorphisms where different alleles corresponded to distinct, non-homologous clusters, and location polymorphisms in which a cluster was found to differ in its genomic location across strains. These polymorphisms affect the function of representative A. fumigatus SM gene clusters, such as those involved in the production of gliotoxin, fumigaclavine, and helvolic acid, as well as the function of clusters with undefined products. In addition to enabling the identification of polymorphisms whose detection requires extensive genome-wide synteny conservation (e.g., mobile gene clusters and non-homologous cluster alleles), our approach also implicated multiple underlying genetic drivers, including point mutations, recombination, genomic deletion and insertion events, as well as horizontal gene transfer from distant fungi. Finally, most of the variants that we uncover within A. fumigatus have been previously hypothesized to contribute to SM gene cluster diversity across entire fungal classes and phyla. We suggest that the drivers of genetic diversity operating within a fungal species shown here are sufficient to explain SM cluster macroevolutionary patterns.

genomics↗