Biology subjects

Dirks, R. P.

Publications and source records attributed to Dirks, R. P..

9 recordsLinked to original sources

bioRxiv2026

The genome assembly of Sphaerospora molnari provides novel insights into the rapid evolution and diversification of unique lineage-specific gene groups in myxozoan parasites

BackgroundMyxozoans are ancient cnidarian parasites with highly derived genomes characterized by an extremely accelerated rate of nucleotide substitution, abundant orphan and lineage-specific genes without further characterization. Genome data are limited to two out of the four main evolutionary lineages, assemblies are highly fragmented and often show significant levels of host contamination. ResultsWe present a near chromosome-scale myxozoan genome, based on Oxford Nanopore-reads of Sphaerospora molnari, a member of the previously uncharacterized group of blood-feeding myxozoans, thereby addressing a key gap in the subphylums phylogeny. The haploid genome assembly spans 40.17 Mb in 40 contigs, harbors 14,957 genes and shows the smallest mitogenome of myxozoans (14,015 bp). Gene gain/gene loss analyses showed that myxozoans have small ancestral gene repertoires and show highly lineage-specific genome compositions. Using comparative analyses focusing on identifying unique but diversified gene compartments in S. molnari, we discovered taxonomically restricted protist genes related to red blood cell attachment (Plasmodium ETRAMPs) and surface protein variation (Plasmodium variant surface antigen families RIFIN and STEVOR, as well as Metamonada variant-specific surface proteins, VSPs), raising questions about their origins and evolution. A genomic trait shared between several myxozoans is the significant expansion of DNA transposable elements belonging to the mutator-like elements (MULEs), and while the simple copy-paste mechanism of these transposases may suggest frequent uncontrolled mutation, we demonstrate domestication of MULEs into transcription factors. Analyses of the gene fragments of chimeric MULEs (pack-MULES) of S. molnari show that these coincide with highly diversified gene groups in this lineage, including alien genes, suggesting MULEs as a driving force for gene evolution in myxozoans. ConclusionsParasitic lifestyle shifts drive exceptionally rapid genome evolution in myxozoans, primarily through nonadaptive mutation and gene transfer via MULEs, with adaptive refinement through MULE domestication and selection. In S. molnari, these processes underpin unique erythrocyte exploitation and immune evasion strategies essential for survival in the hosts bloodstream.

genomics↗

bioRxiv2025

Discovery of iridoid cyclase completes the iridoid pathway in asterids

Iridoids are specialized monoterpenes ancestral to asterid flowering plants (Albach et al, 2001; Stull et al, 2018). Iridoids play key roles in plant defense and are also essential precursors for pharmacologically important alkaloids (Dobler et al, 2011; Eisner, 1964). The biosynthesis of all iridoids involves the cyclization of a reactive enol intermediate. While this cyclization occurs spontaneously at low yields, it has long been hypothesized that a dedicated enzyme is involved in this process (Geu-Flores et al, 2012; Lichman et al, 2019b). Here, we report the discovery of asterid iridoid cyclases (ICYC). We show that these enzymes catalyze cyclization of the reactive intermediate to form the two major iridoid stereoisomers found in plants. Our work uncovers the last missing key step in the otherwise well-characterized iridoid biosynthesis pathway in asterids. This discovery unlocks the possibility to generate previously inaccessible iridoid stereoisomers, which will enable metabolic engineering for the sustainable production of valuable iridoid and iridoid-derived compounds.

plant biology↗

bioRxiv2024

Comparative genomics of Rickettsiella bacteria reveal variable metabolic traits involved in symbiotic interactions with arthropods

Members of the Rickettsiella genus (order: Legionellales) are emerging as widespread bacteria associated with insects, arachnids, and crustaceans. While some Rickettsiella strains are highly virulent pathogens, others are maternally inherited endosymbionts that manipulate arthropod phenotypes, including the induction of defensive symbiosis and cytoplasmic incompatibility. However, the genomic diversity of Rickettsiella remains largely unexplored, and their genetic potential to induce complex phenotypes in arthropods is only partially understood. In this study, we sequenced five new Rickettsiella genomes isolated from three tick species. Through comparative genomics, we observed that Rickettsiella members share similar metabolic capabilities, and collectively lack virulence genes from pathogenic Legionellales. Additional analysis of Rickettsiella genomes revealed significant variability in metabolic properties related to endosymbiosis. Specifically, their capacity to biosynthesize certain B vitamins and heme varies, suggesting a functional role of some Rickettsiella strains in the nutrition of their arthropod hosts. Some Rickettsiella genomes harbour homologs of Wolbachia cif genes, the cause of Wolbachia-induced cytoplasmic incompatibility,, suggesting that Rickettsiella may use a similar molecular mechanism to manipulate the reproduction of their arthropod hosts. Phylogenomics further revealed that tick-borne Rickettsiella exhibit distinct evolutionary origins within the genus, indicating that Rickettsiella have undergone repeated horizontal transfers between ticks and other arthropods.

evolutionary biology↗

bioRxiv2024

The human pathogen Mycobacterium tuberculosis and the fish pathogen Mycobacterium marinum trigger the same core set of late innate immune response genes in zebrafish larvae

Zebrafish is a natural host of various Mycobacterium species and a surrogate model organism for tuberculosis research. Mycobacterium marinum is evolutionarily one of the closest non-tuberculous species related to M. tuberculosis and shares the majority of virulence genes. Although zebrafish is not a natural host of the human pathogen, we have previously demonstrated successful robotic infection of zebrafish embryos with M. tuberculosis and performed drug treatment of the infected larvae. In the present study we examined for how long M. tuberculosis can be propagated in zebrafish larvae and tested a time series of infected larvae to study the transcriptional response via Illumina RNA deep sequencing (RNAseq). Granuloma-like structures carrying fluorescently labeled M. tuberculosis could be detected up to 9 days post infection. The continued presence of viable M. tuberculosis in the zebrafish larvae was further confirmed using the molecular bacterial load (MBL) assay. The infected larvae showed a clear and specific transcriptional immune response with a high similarity to the response of zebrafish larvae infected with the surrogate species M. marinum. We conclude that M. tuberculosis can be propagated in zebrafish larvae for at least one week after infection and provide further evidence that M. marinum is a good surrogate model for M. tuberculosis.

immunology↗

bioRxiv2024

Metabolic engineering of yeast for de novo production of kratom monoterpene indole alkaloids

Monoterpene indole alkaloids (MIAs) from Mitragyna speciosa ("kratom"), such as mitragynine and speciogynine, are promising novel scaffolds for opioid receptor ligands for treatment of pain, addiction, and depression. While kratom leaves have been used for centuries in South-East Asia as stimulant and pain management substance, the biosynthetic pathway of these psychoactives have only recently been partially elucidated. Here, we demonstrate the de novo production of mitragynine and speciogynine in Saccharomyces cerevisiae through the reconstruction of a five-step synthetic pathway from common MIA precursor strictosidine comprising fungal tryptamine 4-monooxygenase to bypass an unknown kratom hydroxylase. Upon optimizing cultivation conditions, a titer of [~]290 {micro}g/L kratom MIAs from glucose was achieved. Untargeted metabolomics analysis of lead production strains led to the identification of numerous shunt products derived from the activity of strictosidine synthase (STR) and dihydrocorynantheine synthase (DCS), highlighting them as candidates for enzyme engineering to further improve kratom MIAs production in yeast. Finally, by feeding fluorinated tryptamine and expressing a human tailoring enzyme, we further demonstrate production of fluorinated and hydroxylated mitragynine derivatives with potential applications in drug discovery campaigns. Altogether, this study introduces a yeast cell factory platform for the biomanufacturing of complex natural and new-to-nature kratom MIAs derivatives with therapeutic potential.

synthetic biology↗

bioRxiv2024

Deep sequencing of 16 Ixodes ricinus ticks unveils insights into their interactions with endosymbionts.

BackgroundIxodes ricinus ticks act as vectors for numerous pathogens that present substantial health threats. Additionally, they harbour vertically transmitted symbionts, some of which have been linked to diseases. The difficulty of isolating and cultivating these symbionts has hampered our understanding of their biological role, their potential to cause disease, and their modes of transmission. To expand our understanding on the tick symbiont Midichloria mitochondrii and on Rickettsia helvetica, which has been linked to disease in humans, we utilized deep sequencing on sixteen individual adult female ticks collected from coastal dune and forested areas in the Netherlands. ResultsBy employing a combination of second and third-generation sequencing techniques, we successfully reconstructed the complete genomes of M. mitochondrii from eleven individuals, R. helvetica from eight individuals and the mitochondrial genome from all ticks. Additionally, we visualised the location of R. helvetica in tick organs and constructed genome-scale metabolic models (GEMs) of both symbionts to study their environmental dependencies. Our analysis revealed a strong cophylogeny between M. mitochondrii and mitochondrial genomes, suggesting frequent maternal transmission. In contrast, the absence of cophylogeny between R. helvetica and the mitochondrial genomes, coupled with its presence in the receptaculum seminis of I. ricinus females, raises the possibility of paternal transmission of R. helvetica. Notably, the genetic diversity of R. helvetica was found to be very low, except for the rickA virulence gene, where the presence of up to thirteen insertions of a33nt-long repeat led to significant variability. However, this variation could not account for the differences in infection prevalence observed across eight distinct locations in the Netherlands. ConclusionsBy employing deep sequencing, it becomes feasible to extract complete genomes and genetic data of symbionts directly from their host organisms. This methodology serves as a robust means to gain fresh insights into their interactions. Our observations, which suggest paternal transmission of R. helvetica, a relatively unexplored mode of transmission in ticks, require validation through experimental investigations. The genetic variations identified in the rickA virulence gene of R. helvetica have the potential to influence the infectivity and transmission dynamics of R. helvetica

microbiology↗

bioRxiv2022

Genome structures resolve the early diversification of teleost fishes

Accurate species phylogenies are a prerequisite for evolutionary research. Teleosts are by far the largest and the most diversified group of extant vertebrates, but relationships among the three oldest lineages of extant teleosts remain unresolved. Based on seven high-quality new genome assemblies in Elopomorpha (tarpons, eels), we revisited the topology of the deepest branches of the teleost phylogeny using independent gene sequence and chromosomal rearrangement phylogenomic approaches. These analyses converged to a single scenario that unambiguously places the Elopomorpha and Osteoglossomorpha (bony-tongues) in a monophyletic group sister to all other teleosts, i.e., the Clupeocephala lineage. This finding resolves over 50 years of controversy on the evolutionary relationships of these lineages and highlights the power of combining different levels of genome-wide information to solve complex phylogenies. One-Sentence SummaryWhole-genome analyses place Elopomorpha (tarpons, eels) and Osteoglossomorpha (bony-tongues) as sister groups at the deepest branching of crown teleosts.

evolutionary biology↗

bioRxiv2021

Genome and transcriptome analysis of the beet armyworm Spodoptera exigua reveals targets for pest control

BackgroundThe genus Spodoptera (Lepidoptera: Noctuidae) includes some of the most infamous insect pests of cultivated plants including Spodoptera frugiperda, Spodoptera litura and Spodoptera exigua. To effectively develop targeted pest control strategies for diverse Spodoptera species, genomic resources are highly desired. To this aim, we provide the genome assembly and developmental transcriptome comprising all major life stages of S. exigua, the beet armyworm. Spodoptera exigua is a polyphagous herbivore that can feed from > 130 host plants including several economically important crops. ResultsThe 419 Mb beet armyworm genome was sequenced from a female S. exigua pupa. Using a hybrid genome sequencing approach (Nanopore long read data and Illumina short read), a high-quality genome assembly was achieved (N50=1.1 Mb). An official gene set (OGS, 18,477 transcripts) was generated by automatic annotation and by using transcriptomic RNA-seq data sets of 18 S. exigua samples as supporting evidence. In-depth analyses of developmental stage-specific expression in combination with gene tree analyses of identified homologous genes across Lepidoptera genomes revealed potential Spodoptera-specific genes of interest such as mg7 and REPAT46 upregulated during 1st and 3rd instar larval stages for targeted pest-outbreak management. ConclusionsThe beet armyworm genome sequence and developmental transcriptome covering all major developmental stages provides critical insights into the biology of this devastating polyphagous insect pest species with a worldwide distribution. In addition, comparative genomic analyses across Lepidoptera significantly advance our knowledge to further control other invasive Spodoptera species and reveals potential lineage-specific target genes for pest control strategies.

genomics↗

bioRxiv2017

Rapid de novo assembly of the European eel genome from nanopore sequencing reads

We have sequenced the genome of the endangered European eel using the MinION by Oxford Nanopore, and assembled these data using a novel algorithm specifically designed for large eukaryotic genomes. For this 860 Mbp genome, the entire computational process takes two days on a single CPU. The resulting genome assembly significantly improves on a previous draft based on short reads only, both in terms of contiguity (N50 1.2 Mbp) and structural quality. This combination of affordable nanopore sequencing and light-weight assembly promises to make high-quality genomic resources accessible for many non-model plants and animals.

genomics↗