Biology subjects

Wisecaver, J. H.

Publications and source records attributed to Wisecaver, J. H..

15 recordsLinked to original sources

bioRxiv2026

Hybridization between toxic bloom-forming algae of the Prymnesium parvum sensu lato species complex

The potential for hybridization to act as a driver of genetic diversity and adaptation in harmful algal bloom-forming species has received scarce attention, despite growing recognition of its occurrence in diverse protist and algal lineages. Prymnesium parvum s.l. (Haptophyta), is a cryptic species complex whose members form ecosystem-disruptive toxic algal blooms around the world. A prior genome analysis showed that UTEX2797, a widely used laboratory strain, originated via hybridization between clade A1 and clade A2 of this species complex. To assess the extent of A1xA2 hybridization in P. parvum s.l., we screened the genomes of 28 strains and identified 16 additional A1xA2 hybrid strains isolated from inland Texas or the eastern United States between 2001 and 2020. Chloroplast haplotypes indicated that hybridization between A1 and A2 may have occurred multiple times, and hybrids with different chloroplast haplotypes have been co-isolated from blooms in Texas in 2013 and 2020. Additionally, strain NIES1812 from Okinawa, Japan was sufficiently divergent from A1 and A2 to warrant designation as a separate clade, which we name A3. These results provide evidence for a facultative sexual life cycle in P. parvum s.l. and expand our understanding of the extensive cryptic genetic diversity present in the species complex. The frequent isolation of hybrid strains from North American blooms suggests that hybridization is common and represents a significant source of adaptive potential in these economically and ecologically damaging organisms.

evolutionary biology↗

bioRxiv2024

A brassinosteroid receptor kinase is required for sex determination in the homosporous fern Ceratopteris richardii

Most ferns, unlike all seed plants, are homosporous and produce sexually undifferentiated spores. Sex in many homosporous ferns is environmentally regulated by the biosynthesis of antheridiogens. Secreted antheridiogen from female or hermaphrodite gametophytes is perceived by undetermined gametophytes which respond by developing as male. In the fern Ceratopteris richardii (Ceratopteris), several hermaphroditic (her) mutants develop as hermaphrodites even in the presence of antheridiogen. A set of five mutant alleles are tightly linked to her7, a locus of unknown molecular identity. The immense size of the Ceratopteris genome has made efficient identification of the underlying genes a challenge. Here, we used bulked segregant RNA-seq (BSR-Seq) to map two her mutants (her7-14 and her7-19) to a 16 Mbp interval on chromosome 29 of the Ceratopteris genome. A brassinosteroid receptor-like kinase (BRL) within this interval encoded a deletion mutation in her7-14 and a missense mutation in her7-19. Three other linked her mutants (her7-1, her7-11, and her7-15) encoded missense mutations in the same gene, which we name HER7, providing strong support for HER7 being required for antheridiogen-mediated sex determination in Ceratopteris. HER7-GFP fusion protein is localized in the plasma membrane and cytoplasm, consistent with its predicted function as a brassinosteroid receptor kinase. RNA-seq analysis of gene expression shows that numerous transcripts encoding enzymes, including those for brassinosteroid biosynthesis, accumulate in hermaphrodites compared to male gametophytes. The antheridiogen of Ceratopteris is currently unknown and our finding that a BRL mutant is insensitive to antheridiogen suggests that antheridiogen in Ceratopteris may be a brassinosteroid. Additional work is required to fully resolve the sex determination pathway and determine the chemical composition of antheridiogen in this species. Our work demonstrates we can identify the molecular basis of mutants in large genomes, such as those in homosporous ferns, which can be further applied to the extensive remaining collection of mutants in Ceratopteris.

genetics↗

bioRxiv2024

Candida glabrata maintains two Hap1 homologs, Zcf27 andZcf4, for distinct roles in ergosterol gene regulation to mediate sterol homeostasis under azole and hypoxic conditions

Candida glabrata exhibits innate resistance to azole antifungal drugs but also has the propensity to rapidly develop clinical drug resistance. Azole drugs, which target Erg11, is one of the three major classes of antifungals used to treat Candida infections. Despite their widespread use, the mechanism controlling azole-induced ERG gene expression and drug resistance in C. glabrata has primarily revolved around Upc2 and/or Pdr1. In this study, we determined the function of two zinc cluster transcription factors, Zcf27 and Zcf4, as direct but distinct regulators of ERG genes. Our phylogenetic analysis revealed C. glabrata Zcf27 and Zcf4 as the closest homologs to Saccharomyces cerevisiae Hap1. Hap1 is a known zinc cluster transcription factor in S. cerevisiae in controlling ERG gene expression under aerobic and hypoxic conditions. Interestingly, when we deleted HAP1 or ZCF27 in either S. cerevisiae or C. glabrata, respectively, both deletion strains showed altered susceptibility to azole drugs, whereas the strain deleted for ZCF4 did not exhibit azole susceptibility. We also determined that the increased azole susceptibility in a zcf27{Delta} strain is attributed to decreased azole-induced expression of ERG genes, resulting in decreased levels of total ergosterol. Surprisingly, Zcf4 protein expression is barely detected under aerobic conditions but is specifically induced under hypoxic conditions. However, under hypoxic conditions, Zcf4 but not Zcf27 was directly required for the repression of ERG genes. This study provides the first demonstration that Zcf27 and Zcf4 have evolved to serve distinct roles allowing C. glabrata to adapt to specific host and environmental conditions. IMPORTANCEInvasive and drug-resistant fungal infections pose a significant public health concern. Candida glabrata, a human fungal pathogen, is often difficult to treat due to its intrinsic resistance to azole antifungal drugs and its capacity to develop clinical drug resistance. Therefore, understanding the pathways that facilitate fungal growth and environmental adaptation may lead to novel drug targets and/or more efficacious antifungal therapies. While the mechanisms of azole resistance in Candida species have been extensively studied, the roles of zinc cluster transcription factors, such as Zcf27 and Zcf4, in C. glabrata have remained largely unexplored until now. Our research shows that these factors play distinct yet crucial roles in regulating ergosterol homeostasis under azole drug treatment and oxygen-limiting growth conditions. These findings offer new insights into how this pathogen adapts to different environmental conditions and enhances our understanding of factors that alter drug susceptibility and/or resistance.

genetics↗

bioRxiv2024

Giant polyketide synthase enzymes biosynthesize a giant marine polyether biotoxin.

Prymnesium parvum are harmful haptophyte algae that cause massive environmental fish-kills. Their polyketide polyether toxins, the prymnesins, are amongst the largest nonpolymeric compounds in nature, alongside structurally-related health-impacting "red-tide" polyether toxins whose biosynthetic origins have been an enigma for over 40 years. Here we report the PKZILLAs, massive P. parvum polyketide synthase (PKS) genes, whose existence and challenging genomic structure evaded prior detection. PKZILLA-1 and -2 encode giant protein products of 4.7 and 3.2 MDa with 140 and 99 enzyme domains, exceeding the largest known protein titin and all other known PKS systems. Their predicted polyene product matches the proposed pre-prymnesin precursor of the 90-carbon-backbone A-type prymnesins. This discovery establishes a model system for microalgal polyether biosynthesis and expands expectations of genetic and enzymatic size limits in biology.

genomics↗

bioRxiv2023

A reference genome for the long-term kleptoplast-retaining sea slug Elysia crispata morphotype clarki

Several species of sacoglossan sea slugs possess the incredible ability to sequester chloroplasts from the algae they consume. These photosynthetic animals incorporate stolen chloroplasts, called kleptoplasts, into the epithelial cells of tubules that extend from their digestive tracts throughout their bodies. The mechanism by which these slugs maintain functioning kleptoplasts in the absence of an algal nuclear genome is unknown. Here, we report a draft genome of the saccoglossan slug Elysia crispata morphotype clarki, a morphotype native to the Florida Keys that can retain photosynthetically active kleptoplasts for several months without feeding. We used a combination of Oxford Nanopore Technologies long reads and Illumina short reads to produce a 786 Mbp assembly containing 68,514 predicted protein-coding genes. A phylogenetic analysis found no evidence of horizontal acquisition of genes from algae. We performed gene family and gene expression analyses to identify E. crispata genes unique to kleptoplast-containing slugs that were more highly expressed in fed versus unfed developmental life stages. Consistent with analyses in other kleptoplastic slugs, our investigation suggests that genes encoding lectin carbohydrate-binding proteins and those involved in regulation of reactive oxygen species and immunity may play a role in kleptoplast retention. Lastly, we identified four polyketide synthase genes that could potentially encode proteins producing UV- and oxidation-blocking compounds in slug cell membranes. The genome of E. crispata is a quality resource that provides potential targets for functional analyses and enables further investigation into the evolution and mechanisms of kleptoplasty in animals.

genomics↗

bioRxiv2022

Extreme genome diversity and cryptic speciation in a harmful algal bloom forming eukaryote

Harmful algal blooms (HABs) of the toxic haptophyte Prymnesium parvum are a recurrent problem in many inland and estuarine waters around the world. Strains of P. parvum vary in the toxins they produce and in other physiological traits associated with HABs, but the genetic basis for this variation is unknown. To investigate genome diversity in this morphospecies, we generated genome assemblies for fifteen phylogenetically and geographically diverse strains of P. parvum including Hi-C guided, near-chromosome level assemblies for two strains. Comparative analysis revealed considerable DNA content variation between strains, ranging from 115 Mbp to 845 Mbp. Strains included haploids, diploids, and polyploids, but not all differences in DNA content were due to variation in genome copy number. Haploid genome size between strains of different chemotypes differed by as much as 243 Mbp. Syntenic and phylogenetic analyses indicate that UTEX 2797, a common laboratory strain from Texas, is a hybrid that retains two phylogenetically distinct haplotypes. Investigation of gene families variably present across strains identified several functional categories associated with metabolism, including candidates for the biosynthesis of toxic metabolites, as well as genome size variation, including recent proliferations of transposable elements. Together, our results indicate that P. parvum is comprised of multiple cryptic species. These genomes provide a robust phylogenetic and genomic framework for investigations into the eco-physiological consequences of the intra- and inter-specific genetic variation present in P. parvum and demonstrate the need for similar resources for other HAB-forming morphospecies. SIGNIFICANCE STATEMENTHarmful algal blooms (HABs) are a global concern. Efforts to understand the genetic basis of traits associated with the success of HAB-forming species are limited by a dearth of genomic resources. In this paper we present genomes for fifteen strains of Prymnesium parvum, a toxic alga that causes ecosystem and societally disruptive HABs around the world. We uncover an unprecedented amount of sequence-level, gene family, and genome architecture evolution in P. parvum and provide evidence for both cryptic speciation and hybridization. These results illustrate how both inter- and intraspecific genetic variation can be dramatically underestimated in a protist morphospecies. More work is needed to understand the eco-physiological consequences of hidden genetic diversity in P. parvum and HAB-forming species more generally.

evolutionary biology↗

bioRxiv2021

Integrative analysis of the shikonin metabolic network identifies new gene connections and reveals evolutionary insight into shikonin biosynthesis

Plant specialized 1,4-naphthoquinones present a remarkable case of convergent evolution. Species across multiple discrete orders of vascular plants produce diverse 1,4-naphthoquinones via one of several pathways using different metabolic precursors. Evolution of these pathways was preceded by events of metabolic innovation and many appear to share connections with biosynthesis of photosynthetic or respiratory quinones. Here, we sought to shed light on the metabolic connections linking shikonin biosynthesis with its precursor pathways and on the origins of shiknoin metabolic genes. Downregulation of Lithospermum erythrorhizon geranyl diphosphate synthase (LeGPPS), recently shown to have been recruited from a cytoplasmic farnesyl diphosphate synthase (FPPS), resulted in reduced shikonin production and a decrease in expression of mevalonic acid and phenylpropanoid pathway genes. Next, we used LeGPPS and other known shikonin pathway genes to build a coexpression network model for identifying new gene connections to shikonin metabolism. Integrative in silico analyses of network genes revealed candidates for biochemical steps in the shikonin pathway arising from Boraginales-specific gene family expansion. Multiple genes in the shikonin coexpression network were also discovered to have originated from duplication of ubiquinone pathway genes. Taken together, our study provides evidence for transcriptional crosstalk between shikonin biosynthesis and its precursor pathways, identifies several shikonin pathway gene candidates and their evolutionary histories, and establishes additional evolutionary links between shikonin and ubiquinone metabolism. Moreover, we demonstrate that global coexpression analysis using limited transcriptomic data obtained from targeted experiments is effective for identifying gene connections within a defined metabolic network.

plant biology↗

bioRxiv2021

Secondary metabolism drives ecological breadth in the Xylariaceae

Global, large-scale surveys of phylogenetically diverse plant and lichen hosts have revealed an extremely high richness of endophytes in the Xylariales, one of the largest clades of filamentous fungi and a significant source of novel secondary metabolites (SMs). Endophytes may produce host protective antimicrobial or insecticidal SMs, as well as compounds that facilitate symbiotic establishment through suppression or degradation of host immune response, but the ecological roles of most SMs are unknown. Here we characterized metabolic gene clusters in 96 genomes of endophytes and closely related saprotrophs and pathogens in two clades of Xylariales (Xylariaceae s.l. and Hypoxylaceae). Hundreds of genes appear horizontally transferred to xylarialean fungi from distantly related fungi and bacteria, including numerous genes in secondary metabolite gene clusters (SMGCs). Although all xylarialean genomes contain hyperabundant SMGCs, we show that increased gene duplications, horizontal gene transfers (HGTs), and SMGC content in Xylariaceae s.l. taxa are linked to greater phylogenetic host breadth, larger biogeographic distributions, and increased capacity for lignocellulose decomposition compared to Hypoxylaceae taxa. Overall, our results suggest that xylarialean endophytes capable of dual ecological modes (symbiotic and saprotrophic) experience greater selection to diversify SMGCs to both increase competitiveness within microbial communities and facilitate diverse symbiotic interactions.

genomics↗

bioRxiv2020

Reference genome for the highly transformable Setaria viridis cultivar ME034V

Setaria viridis (green foxtail) is an important model system for improving cereal crops due to its diploid genome, ease of cultivation, and use of C4 photosynthesis. The S. viridis cultivar ME034V is exceptionally transformable, but the lack of a sequenced genome for this cultivar has limited its utility. We present a 397 Mb highly contiguous de novo assembly of ME034V using ultra-long nanopore sequencing technology (read N50=41kb). We estimate that this genome is largely complete based on our updated k-mer based genome size estimate of 401 Mb for S. viridis. Genome annotation identified 37,908 protein-coding genes and >300k repetitive elements comprising 46% of the genome. We compared the ME034V assembly with two other previously sequenced Setaria genomes as well as to a diversity panel of 235 S. viridis cultivars. We found the genome assemblies to be largely syntenic, but numerous unique polymorphic structural variants were discovered. Several ME034V deletions may be associated with recent retrotransposition of copia and gypsy LTR repeat families, as evidenced by their low genotype frequencies in the sampled population. Lastly, we performed a phylogenomic analysis to identify gene families that have expanded in Setaria, including those involved in specialized metabolism and plant defense response. The high continuity of the ME034V genome assembly validates the utility of ultra-long DNA sequencing to improve genetic resources for emerging model organisms. Structural variation present in Setaria illustrates the importance of obtaining the proper genome reference for genetic experiments. Thus, we anticipate that the ME034V genome will be of significant utility for the Setaria research community.

genomics↗

bioRxiv2020

Beyond the biosynthetic gene cluster paradigm: Genome-wide co-expression networks connect clustered and unclustered transcription factors to secondary metabolic pathways

Fungal secondary metabolites are widely used as therapeutics and are vital components of drug discovery programs. A major challenge hindering discovery of novel secondary metabolites is that the underlying pathways involved in their biosynthesis are transcriptionally silent in typical laboratory growth conditions, making it difficult to identify the transcriptional networks that they are embedded in. Furthermore, while the genes participating in secondary metabolic pathways are typically found in contiguous clusters on the genome, known as biosynthetic gene clusters (BGCs), this is not always the case, especially for global and pathway-specific regulators of pathways activities. To address these challenges, we used 283 genome-wide gene expression datasets of the ascomycete cell factory Aspergillus niger generated during growth under 155 different conditions to construct two gene co-expression networks based on Spearmans correlation coefficients (SCC) and on mutual rank-transformed Pearsons correlation coefficients (MR-PCC). By mining these networks, we predicted six transcription factors named MjkA - MjkF to concomitantly regulate secondary metabolism in A. niger. Over-expression of each transcription factor using the Tet-on cassette modulated production of multiple secondary metabolites. We found that the SCC and MR-PCC approaches complemented each other, enabling the delineation of global (SCC) and pathway-specific (MR-PCC) transcription factors, respectively. These results highlight the great potential of co-expression network approaches to identify and activate fungal secondary metabolic pathways and their products. More broadly, we argue that novel drug discovery programs in fungi should move beyond the BGC paradigm and focus on understanding the global regulatory networks in which secondary metabolic pathways are embedded. ImportanceThere is an urgent need for novel bioactive molecules in both agriculture and medicine. The genomes of fungi are thought to contain vast numbers of metabolic pathways involved in the biosynthesis of secondary metabolites with diverse bioactivities. Because these metabolites are biosynthesized only under specific conditions, the vast majority of fungal pharmacopeia awaits discovery. To discover the genetic networks that regulate the activity of secondary metabolites, we examined the genome-wide profiles of gene activity of the cell factory Aspergillus niger across hundreds of conditions. By constructing global networks that link genes with similar activities across conditions, we identified six global and pathway-specific regulators of secondary metabolite biosynthesis. Our study shows that elucidating the behavior of the genetic networks of fungi under diverse conditions harbors enormous promise for understanding fungal secondary metabolism, which ultimately may lead to novel drug candidates.

microbiology↗

bioRxiv2019

Horizontal transfer of prokaryotic cytolethal distending toxin B genes to eukaryotes

Cytolethal distending toxins (CDTs) are tripartite eukaryotic genotoxins encoded in diverse bacterial and phage genomes. The cdtB subunit is a DNAse that causes eukaryotic cell cycle arrest and apoptosis, and in one context, is associated with resistance against parasitoid wasp infections. Here we report the discovery of functional cdtB copies in the nuclear genomes of insect species from two distantly related insect orders, including fruit flies (Diptera: Drosophilidae) and aphids (Hemiptera: Aphididae). Insect cdtB copies are most closely related to bacteriophage copies, were horizontally transferred to insect genomes > 40 million years ago and encode a protein that retains ancestral DNase activity. This phage-derived toxin has been domesticated by diverse insects and we hypothesize that it is used as a defensive weapon against parasitoid wasps. One Sentence SummaryWe report horizontal transfer of the gene cytolethal distending toxin B, which encodes a DNase, into eukaryotic genomes from bacteriophage. SignificanceCytolethal distending toxins (CDTs) are secreted by diverse pathogenic bacterial species to kill animal cells. The cdtB subunit enters cell nuclei, damaging the DNA and leading to mitotic arrest and apoptosis. In the pea aphid, a bacterial endosymbiont provides protection against wasp attack, possibly via cdtB. We discovered that this same endosymbiont-encoded lineage of cdtB was transferred to the genomes of Diptera and Hemiptera species and retains ancestral DNase activity. This is the first report of cdtB outside of bacteria or phages. A toxin that first evolved to kill eukaryotic cells has been co-opted by insects, potentially to their benefit.

evolutionary biology↗

bioRxiv2018

integRATE: a desirability-based data integration framework for the prioritization of candidate genes across heterogeneous omics and its application to preterm birth

BackgroundThe integration of high-quality, genome-wide analyses offers a robust approach to elucidating genetic factors involved in complex human diseases. Even though several methods exist to integrate heterogeneous omics data, most biologists still manually select candidate genes by examining the intersection of lists of candidates stemming from analyses of different types of omics data that have been generated by imposing hard (strict) thresholds on quantitative variables, such as P-values and fold changes, increasing the chance of missing potentially important candidates.\n\nMethodsTo better facilitate the unbiased integration of heterogeneous omics data collected from diverse platforms and samples, we propose a desirability function framework for identifying candidate genes with strong evidence across data types as targets for follow-up functional analysis. Our approach is targeted towards disease systems with sparse, heterogeneous omics data, so we tested it on one such pathology: spontaneous preterm birth (sPTB).\n\nResultsWe developed the software integRATE, which uses desirability functions to rank genes both within and across studies, identifying well-supported candidate genes according to the cumulative weight of biological evidence rather than based on imposition of hard thresholds of key variables. Integrating 10 sPTB omics studies identified both genes in pathways previously suspected to be involved in sPTB as well as novel genes never before linked to this syndrome. integRATE is available as an R package on GitHub (https://github.com/haleyeidem/integRATE).\n\nConclusionsDesirability-based data integration is a solution most applicable in biological research areas where omics data is especially heterogeneous and sparse, allowing for the prioritization of candidate genes that can be used to inform more targeted downstream functional analyses.

genomics↗

bioRxiv2017

Evidence for loss and adaptive reacquisition of alcoholic fermentation in an early-derived fructophilic yeast lineage

Fructophily is a rare trait that consists in the preference for fructose over other carbon sources. Here we show that in a yeast lineage (the Wickerhamiella/Starmerella, W/S clade) formed by fructophilic species thriving in the floral niche, the acquisition of fructophily is part of a wider process of adaptation of central carbon metabolism to the high sugar environment. Coupling comparative genomics with biochemical and genetic approaches, we show that the alcoholic fermentation pathway was profoundly remodeled in the W/S clade, as genes required for alcoholic fermentation were lost and subsequently re-acquired from bacteria through horizontal gene transfer. We further show that the reinstated fermentative pathway is functional and that an enzyme required for sucrose assimilation is also of bacterial origin, reinforcing the adaptive nature of the genetic novelties identified in the W/S clade. This work shows how even central carbon metabolism can be remodeled by a surge of HGT events.

genomics↗

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↗

bioRxiv2016

A global co-expression network approach for connecting genes to specialized metabolic pathways in plants

Plants produce a tremendous diversity of specialized metabolites (SMs) to interact with and manage their environment. A major challenge hindering efforts to tap this seemingly boundless source of pharmacopeia is the identification of SM pathways and their constituent genes. Given the well-established observation that the genes comprising a SM pathway are co-regulated in response to specific environmental conditions, we hypothesized that genes from a given SM pathway would form tight associations (modules) with each other in gene co-expression networks, facilitating their identification. To evaluate this hypothesis, we used 10 global co-expression datasets--each a meta-analysis of hundreds to thousands of expression experiments--across eight plant model organisms to identify hundreds of modules of co-expressed genes for each species. In support of our hypothesis, 15.3-52.6% of modules contained two or more known SM biosynthetic genes (e.g., cytochrome P450s, terpene synthases, and chalcone synthases), and module genes were enriched in SM functions (e.g., glucoside and flavonoid biosynthesis). Moreover, modules recovered many experimentally validated SM pathways in these plants, including all six known to form biosynthetic gene clusters (BGCs). In contrast, genes predicted based on physical proximity on a chromosome to form plant BGCs were no more co-expressed than the null distribution for neighboring genes. These results not only suggest that most predicted plant BGCs do not represent genuine SM pathways but also argue that BGCs are unlikely to be a hallmark of plant specialized metabolism. We submit that global gene co-expression is a rich, but largely untapped, data source for discovering the genetic basis and architecture of plant natural products, which can be applied even without knowledge of the genome sequence.

plant biology↗