Biology subjects

Kurlovs, A. H.

Publications and source records attributed to Kurlovs, A. H..

5 recordsLinked to original sources

bioRxiv2024

Immune disease dialogue of chemokine-based cell communications as revealed by single-cell RNA sequencing meta-analysis

Immune-mediated diseases are characterized by aberrant immune responses, posing significant challenges to global health. In both inflammatory and autoimmune diseases, dysregulated immune reactions mediated by tissue-residing immune and non-immune cells precipitate chronic inflammation and tissue damage that is amplified by peripheral immune cell extravasation into the tissue. Chemokine receptors are pivotal in orchestrating immune cell migration, yet deciphering the signaling code across cell types, diseases and tissues remains an open challenge. To delineate disease-specific cell-cell communications involved in immune cell migration, we conducted a meta-analysis of publicly available single-cell RNA sequencing (scRNA-seq) data across diverse immune diseases and tissues. Our comprehensive analysis spanned multiple immune disorders affecting major organs: atopic dermatitis and psoriasis (skin), chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis (lung), ulcerative colitis (colon), IgA nephropathy and lupus nephritis (kidney). By interrogating ligand-receptor (L-R) interactions, alterations in cell proportions, and differential gene expression, we unveiled intricate disease- specific and common immune cell chemoattraction and extravasation patterns. Our findings delineate disease-specific L-R networks and shed light on shared immune responses across tissues and diseases. Insights gleaned from this analysis hold promise for the development of targeted therapeutics aimed at modulating immune cell migration to mitigate inflammation and tissue damage. This nuanced understanding of immune cell dynamics at the single-cell resolution opens avenues for precision medicine in immune disease management.

immunology↗

bioRxiv2022

Abundant trans-driven variation in detoxification gene expression in the extreme generalist herbivore Tetranychus urticae

The extreme adaptation potential of the generalist herbivore Tetranychus urticae (the two-spotted spider mite) to pesticides as well as diverse host plants has been associated with clade-specific gene expansions in known detoxifying enzyme families, and with extensive and rapid transcriptional responses. However, how this broad transcriptional potential is regulated remains largely unknown. Using a parental/F1 design in which four inbred strains were crossed to a common inbred strain, we assessed the genetic basis and inheritance of gene expression variation in T. urticae. Mirroring known phenotypic variation in the progenitor strains of the inbreds, we confirmed that the inbred strains we created were genetically distinct, varied markedly in pesticide resistance, and also captured variation in host plant fitness commonly observed in this species. By examining differences in gene expression between parents and allele-specific expression in F1s, we found that variation in RNA abundance was more often explained in trans as compared to cis, with the former associated with dominance in inheritance. Strikingly, in a gene ontology analysis, detoxification genes of the cytochrome P450 monooxygenase (CYP) family, as well as dioxygenases (DOGs) acquired from horizontal gene transfer from fungi, were specifically enriched at the extremes of trans-driven up- and downregulation. In particular, a clade of CYPs with documented broad substrate-specificity including multiple pesticides, as well as DOGs that have recently been shown to have broad substrate specificity against plant specialized compounds, were exceptionally highly upregulated as a result of trans effects (or in some cases synergism of cis and trans) in the most multi-pesticide resistant strains. Collectively, our findings highlight the potential importance of trans-driven expression variation in genes associated with xenobiotic metabolism and host plant use for rapid adaptation in T. urticae, and also suggest modular control of these genes, a regulatory architecture that might ameliorate negative pleiotropic effects. Author summaryThe two-spotted spider mite, Tetranychus urticae, is a generalist herbivore and pest of diverse crops globally. In response to the plethora of chemicals used for its control, the species rapidly evolves pesticide resistance. Further, experimental evolution studies with T. urticae populations have demonstrated adaptation to challenging host plants in as few as five generations. The adaptation of T. urticae to pesticides and host plants has been associated with large transcriptome changes, including for genes associated with detoxification of pesticides and toxic plant compounds. Nevertheless, the basis of the observed transcriptome variation has remained largely unknown. Here, we examined the genetic control and inheritance of expression differences among five inbred T. urticae strains, including several with histories of intense pesticide selection. With a parental/F1 experimental design, we found that trans effects were common in explaining variation in detoxification gene expression, with the trans-driven upregulation of a subset of cytochrome P450 monooxygenases of broad substrate specificity especially striking in the most pesticide resistant strains. Our findings suggest that genetic variation acting with dominant or additive inheritance to impact the regulation of modules of detoxification genes may be an important target of selection during rapid pesticide and host plant evolution in herbivores.

genetics↗

bioRxiv2021

High-resolution genetic mapping reveals cis-regulatory and copy number variation in loci associated with cytochrome P450-mediated detoxification in a generalist arthropod pest

Chemical control strategies are driving the evolution of pesticide resistance in pest populations. Understanding the genetic mechanisms of these evolutionary processes is of crucial importance to develop sustainable resistance management strategies. The acaricide pyflubumide is one of the most recently developed mitochondrial complex II inhibitors with a new mode of action that specifically targets spider mite pests. In this study, we characterize the molecular basis of pyflubumide resistance in a highly resistant population of the spider mite Tetranychus urticae. Classical genetic crosses indicated that pyflubumide resistance was incompletely recessive and controlled by more than one gene. To identify resistance loci, we crossed the resistant population to a highly susceptible T. urticae inbred strain and propagated resulting populations with and without pyflubumide exposure for multiple generations in an experimental evolution set-up. High-resolution genetic mapping by a bulked segregant analysis approach led to the identification of three quantitative trait loci (QTL) linked to pyflubumide resistance. Two QTLs were found on the first chromosome and centered on the cytochrome P450 CYP392A16 and a cluster of CYP392E6-8 genes. Comparative transcriptomics revealed a consistent overexpression of CYP392A16 and CYP392E8 in the experimental populations that were selected for pyflubumide resistance. We further corroborated the involvement of CYP392A16 in resistance by in vitro functional expression and metabolism studies. Collectively, these experiments uncovered that CYP392A16 N-demethylates the toxic carboxamide form of pyflubumide to a non-toxic compound. A third QTL coincided with cytochrome P450 reductase (CPR), a vital component of cytochrome P450 metabolism. We show here that the resistant population harbors three gene copies of CPR and that this copy number variation is associated with higher mRNA abundance. Together, we provide evidence for detoxification of pyflubumide by cytochrome P450s that is likely synergized by gene amplification of CPR. Author summaryOur understanding of the causal genetic variants that drive the evolution of quantitative traits, such as polygenic pesticide resistance, remains very limited. Here, we followed a high-resolution genetic mapping approach to localize the genetic variants that cause pyflubumide resistance in the two-spotted spider mite Tetranychus urticae. Three well-supported QTL were uncovered and pointed towards a major role for cytochrome P450-mediated detoxification. Cis-regulatory variation for cytochrome P450s was observed, and in vitro cytochrome P450 experiments showed that pyflubumide was metabolized into a non-toxic derivate. A third QTL centered on cytochrome P450 reductase (CPR), which is required for cytochrome P450 activity, and is amplified in pyflubumide resistant populations. Our results indicate that pyflubumide resistance is mediated by cytochrome P450 detoxification that is enhanced by gene amplification at the CPR locus. Data availabilitySequence data has been deposited at the Sequence Read Archive (PRJNA596790). Phenotypic quantification data is available at Supplementary Data S1.

genetics↗

bioRxiv2021

Maize inbred line B96 is the source of large-effect loci for resistance to generalist but not specialist spider mites

Maize (Zea mays subsp. mays) yield loss from arthropod herbivory is substantial. While the basis of resistance to major insect herbivores has been comparatively well-studied in maize, less is known about resistance to spider mite herbivores, which are distantly related to insects and feed by a different mechanism. Two spider mites, the generalist Tetranychus urticae, and the grass-specialist Oligonychus pratensis, are notable pests of maize, especially during drought conditions. We assessed the resistance to both mite species of 38 highly diverse maize lines, including several previously reported to be resistant to one or the other mite species. We found that line B96, as well as its derivatives B49 and B75, were highly resistant to T. urticae. In contrast, neither these three lines, nor any others included in our study, were notably resistant to O. pratensis. Quantitative trait locus (QTL) mapping with F2 populations from crosses of B49, B75, and B96 to susceptible B73 identified a large-effect QTL on chromosome 6 as underlying T. urticae resistance in each line, with an additional QTL on chromosome 1 in B96. Genome sequencing and haplotype analyses identified B96 as the apparent sole source of resistance haplotypes. Our study identifies loci for use in maize breeding programs for T. urticae resistance, as well as to assess if the molecular-genetic basis of spider mite resistance is shared with insect pests of maize, as B96 is also among the most resistant known maize lines to several insects, including the European corn borer, Ostrinia nubilalis. Key message Maize(Zea mays subsp. mays) inbred lines B49, B75, and B96 harbor large-effect loci for resistance to the generalist spider mite Tetranychus urticae, but not the specialist Oligonychus pratensis.

genetics↗

bioRxiv2018

Long-term population studies uncover the genome structure and genetic basis of xenobiotic and host plant adaptation in the herbivore Tetranychus urticae

Pesticide resistance arises rapidly in arthropod herbivores, as can host plant adaptation, and both are significant problems in agriculture. These traits have been challenging to study as both are often polygenic and many arthropods are genetically intractable. Here, we examined the genetic architecture of pesticide resistance and host plant adaptation in the two-spotted spider mite, Tetranychus urticae, a global agricultural pest. We show that the short generation time and high fecundity of T. urticae can be readily exploited in experimental evolution designs for high-resolution mapping of quantitative traits. As revealed by selection with spirodiclofen, an acetyl-CoA decarboxylase inhibitor, in populations from a cross between a spirodiclofen resistant and a susceptible strain, and which also differed in performance on tomato, we found that a limited number of loci could explain quantitative resistance to this compound. These were resolved to narrow genomic intervals, suggesting specific candidate genes, including acetyl-CoA decarboxylase itself, clustered and copy variable cytochrome P450 genes, and NADPH cytochrome P450 reductase, which encodes a redox partner for cytochrome P450s. For performance on tomato, candidate genomic regions for response to selection were distinct from those responding to the synthetic compound and were consistent with a more polygenic architecture. In accomplishing this work, we exploited the continuous nature of allele frequency changes across experimental populations to resolve the existing fragmented T.urticae draft genome to pseudochromosomes. This improved assembly was indispensable for our analyses, as it will be for future research with this model herbivore that is exceptionally amenable to genetic studies.

genetics↗