Biology subjects

Keshavarz, M.

Publications and source records attributed to Keshavarz, M..

8 recordsLinked to original sources

bioRxiv2026

Microbiota-pathogen interactions after host death:a potential determinant of pathogen evolution

During the lifetime of many animals, the microbiota fulfills multiple functions. After death of their hosts, these microbes contribute to cadaver decomposition, with implications for forensics, fossilization and soil nutrient and microbial community dynamics. Here, we draw attention to the possibility that host microbiota can also influence the evolution of pathogen lifestyles. We hypothesized that competition between microbiota and pathogens after host death can reduce benefits to pathogens of killing and decomposing their host. To test this hypothesis, we conducted infection experiments in which we injected the entomopathogenic bacteria Pseudomonas entomophila into Tenebrio molitor larvae. Our results show that bacterial proliferation after pathogen-induced host death occurs in larvae with strongly reduced microbiota, but not in larvae with intact gut microbiota. Strikingly, we found that gut microbiota can suppress the proliferation of an about 100 times larger pathogen population. In addition, we identified a microbiota member that might have mediated competitive suppression of pathogen proliferation after host death. Taken together, our results support our hypothesis that decomposing host microbiota can effectively compete with pathogens, thereby reducing the fitness of pathogens that kill and then exploit dead hosts. Based on a reanalysis of an existing theoretical model, we conclude that the host microbiota can facilitate the evolution of more benign pathogens that are less likely to kill their host for cadaver exploitation. Thus, our findings highlight the potentially important but so far unexplored possibility that pathogen-microbiota interactions in dead hosts can affect living hosts by influencing the evolution of pathogens lifestyles.

microbiology↗

bioRxiv2025

Tachykinin-related peptide signalling is important for the immune response of the mealworm beetle Tenebrio molitor L.

Insects possess a well-developed innate immune system, which encompasses both cellular and humoral mechanisms. On the basis of the similarities in neuropeptide actions between insects and vertebrates, we assume that neuropeptides such as tachykinin-related peptides (TRPs) regulate insect immune responses and are themselves modulated following infection. In this study, we examined how immune activation affects the expression of genes encoding TRP precursors and receptors (TRP and TRPR) and whether TRPs directly modulates selected immune mechanisms in the pest species Tenebrio molitor. Our results revealed two important insights. First, after activation of the immune system, TRP and TRPR genes were significantly downregulated in the nervous system and immune-related cells. These changes are closely correlated with the changes of the expression level of immune genes. We then show using Spantide II, a potent antagonist of TRPR, and RNAi knock-down of TRP and TRPR the modulation of key processes of the T. molitor humoral response. This includes the over-expression of genes encoding antimicrobial peptides and the important arthropod immune effector phenoloxidase activity. Our findings highlight a compelling association between the TRP and immune regulation in Tenebrio and provide insights into the hormonal regulation of physiological processes in insects. Our research also provides novel insights that can contribute to the development of sustainable pest control strategies amid increasing insecticide resistance.

immunology↗

bioRxiv2025

Manipulation of the Extracellular Vesicle Biogenesis Pathway in Paternal Somatic Cells Contributes to the Phenotypic Fate of the Next Generation

Human and animal studies have shown that risk factors for certain diseases are linked to our fathers physiological and psychological condition. So far, mainly in vitro evidence indicates extracellular vesicles (EVs) as one of the potential mediators of these paternal effects. In a full in vivo model system, we demonstrate that targeting the EV biogenesis pathway within somatic cells of the male Drosophila melanogaster reproductive tract induces sex-specific phenotypic changes in the progeny. These findings highlight the critical role of the EV pathway in paternal somatic cells in shaping the phenotypic destiny of the next generation and underscore the necessity for further investigations into the mechanisms of somatic to germline information transfer.

physiology↗

bioRxiv2025

Immune-mediated indirect interaction between gut microbiota and bacterial pathogens

BackgroundOrganism survival depends on the ability to orchestrate interactions between the host immune system and gut microbiota in response to pathogenic infections. These tripartite interactions shape pathogen virulence evolution. A key regulator of the immune system and, hence, bipartite interactions (in insects) is the immune deficiency (Imd) pathway, which modulates gut microbiota and pathogens by synthesizing antimicrobial peptides (AMPs). However, whether Imd-dependent AMPs mediate indirect interactions between gut microbiota and pathogens in a tripartite context remains unclear. Using RNAi-mediated knockdown of Tenebrio molitor Relish (TmRelish), we hypothesized that Imd-dependent AMPs influence indirect interaction between Providencia burhodogranaria_B infection and the gut microbiota. ResultsWhile TmRelish-knockdown altered bipartite interactions, disrupting gut microbiota load and composition and increasing pathogen load and virulence through higher host mortality, it did not support our tripartite hypothesis. Instead of Imd-dependent AMPs, gut microbiota and pathogen were influenced by Imd-independent AMPs expression, suggesting alternative regulatory pathways. Nevertheless, our investigations of tripartite interactions showed a positive effect of P. b_B infection on gut microbiota load, while survival analysis further revealed a negative effect of gut microbiota on pathogens infection, suggesting microbiota- mediated immune priming. ConclusionsThese findings suggest that while Imd-dependent AMPs may not mediate tripartite interactions, microbiota-host interactions, such as microbiota-mediated immune priming and changes in microbiota load, can shape infection outcomes. These effects on infection outcomes almost certainly exert important selective pressures on the evolution of bacterial virulence.

immunology↗

bioRxiv2021

Evolution of a new testis-specific functional promotor within the highly conserved Map2k7 gene of the mouse

Map2k7 (synonym Mkk7) is a conserved regulatory kinase gene and a central component of the JNK signaling cascade with key functions during cellular differentiation. It shows complex transcription patterns and different transcript isoforms are known in the mouse (Mus musculus). We have previously identified a newly evolved testis specific transcript for the Map2k7 gene in the subspecies M. m. domesticus. Here, we identify the new promotor that drives this transcript and find that its transcript codes for an open reading frame (ORF) of 50 amino acids. The new promotor was gained in the stem lineage of closely related mouse species, but was secondarily lost in the subspecies M. m. musculus and M. m. castaneus. A single mutation can be correlated with its transcriptional activity in M. m. domesticus and cell culture assays demonstrate the capability of this mutation to drive expression. A mouse knock-out line in which the promotor region of the new transcript is deleted reveals a functional contribution of the newly evolved promotor to sperm motility and to the spermatid transcriptome. Our data show that a new functional transcript (and possibly protein) can evolve within an otherwise highly conserved gene, supporting the notion of regulatory changes contributing to the emergence of evolutionary novelties.

evolutionary biology↗

bioRxiv2020

The imprinted lncRNA Peg13 regulates sexual preference and the gender-specific brain transcriptome in mice

The authors have withdrawn their manuscript because of concerns about the data. Reanalysis of the original transcriptome data files did not confirm the analysis reported in the paper. The conclusions based on the gene sets that are regulated by Peg13 cannot be supported. In addition, original data files recovered for the behavioral data described in Table 2 show several inconsistencies with respect to the values reported in the corresponding supplemental data file S2. Therefore, the authors do not wish this work to be cited as reference for the project. If you have any questions, please contact the corresponding author.

neuroscience↗

bioRxiv2019

Studying the dawn of de novo gene emergence in mice reveals fast integration of new genes into functional networks

The de novo emergence of new transcripts has been well documented through genomic analyses. However, a functional analysis, especially of very young protein-coding genes, is still largely lacking. Here we focus on three loci that have evolved from previously intergenic sequences in the house mouse (Mus musculus) and are not present in its closest relatives. We have obtained knockouts and analyzed their phenotypes, including a deep transcriptomic analysis, based on a dedicated power analysis. We show that the transcriptional networks are significantly disturbed in the knockouts and that all three genes have effects on phenotypes that are related to their expression patterns. This includes behavioral effects, skeletal differences and the regulation of the reproduction cycle in females. Substitution analysis suggests that all three genes have directly obtained an activity, without new adaptive substitutions. Our findings support the hypothesis that de novo genes can quickly adopt functions without extensive adaptation.\n\nImpact statementNew protein-coding genes emerging out of non-coding sequences can become directly functional without signatures of adaptive protein changes

evolutionary biology↗

bioRxiv2018

Copy number variation in small nucleolar RNAs regulates personality behavior

The Prader-Willi Syndrome (PWS) gene region is an imprinted gene complex involved in behavioral, metabolic and osteogenic functions. We have analyzed here the variation of two families of regulatory small nucleolar RNAs (SNORD115 and SNORD116) that are coded within the PWS and are expressed from the paternal chromosome. They are organized in two tandemly repeated clusters which are naturally copy number variable between individuals. We find that the copy numbers at these loci correlate with repeatable individual test scores for anxiety that are considered to constitute a component of the "personality" of individuals. We show this for different populations and species of mice, cavies and for the anxiety component of personality tests in humans. This is also the case for an inbred mouse strain (C57Bl6) implying that copy number variation creates phenotypic variability even in an isogenic background. In transcriptome data from brain samples of this strain we find SNORD copy-number correlated regulation of target genes that are known to be involved in influencing behavior. SNORD115 has previously been suggested to regulate splicing of the serotonin receptor Htr2c and we confirm this in our data. For SNORD116 we provide evidence that it regulates the expression level of the chromatin regulator Ankrd11, which itself regulates GABA receptors, metabolic pathways, cell differentiation and osteogenesis. Intriguingly, we find that craniofacial shapes in mice correlate also with SNORD116 copy numbers. New copy number variants are generated at very high rates in mice, possibly at every generation, explaining why conventional genetic mapping could not detect this association. Our results suggest that the variable dosage of two regulatory RNAs are major determinants of individual behavioral differences and correlated traits in mammals.

evolutionary biology↗