Biology subjects

Kotsyfakis, M.

Publications and source records attributed to Kotsyfakis, M..

3 recordsLinked to original sources

bioRxiv2025

An integrative framework identifies cooperative targeting of host pathways by tick salivary miRNAs

Ticks are ectoparasites that modulate host responses to sustain prolonged blood feeding, and in Ixodes ricinus, salivary microRNAs (miRNAs) represent promising candidates for manipulating host gene expression. Using phylogenetic footprinting combined with cooperative targeting analysis, we identified deeply conserved miRNA-mRNA interactions that appear essential for the tick lifecycle and its ability to parasitize diverse vertebrate hosts. Our findings show that conserved tick miRNAs can mimic host miRNAs by exploiting shared target sites on host transcripts, allowing them to modulate regulatory circuits critical during tick feeding. We identified twelve core salivary miRNAs--highly expressed and enriched in conserved target sites--that cooperatively target twenty-two human genes predominantly expressed in skin and neural tissues. This cooperative suppression converges on host hub genes like PDGFRA and NRG1, linking tick miRNA activity to MAPK and PI3K-AKT pathways that regulate immune defense, tissue repair, and sensory responses. Overall, our results demonstrate that I. ricinus miRNAs can synergistically disrupt host homeostasis, and they introduce a broadly applicable framework that leverages evolutionary conservation to detect meaningful cross-species miRNA-mRNA interactions. HighlightsThe study shows that tick miRNAs with Bilaterian node of origin mimic host miRNAs to exploit conserved target sites of host mRNAs. It demonstrates that these conserved tick miRNAs cooperatively repress key host defense and repair pathways. It introduces a framework that leverages evolutionary conservation to detect and explain functional, conserved cross-species miRNA-mRNA regulation. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=71 SRC="FIGDIR/small/692500v1_ufig1.gif" ALT="Figure 1"> View larger version (23K): org.highwire.dtl.DTLVardef@6eea0aorg.highwire.dtl.DTLVardef@1c739d2org.highwire.dtl.DTLVardef@a53910org.highwire.dtl.DTLVardef@1458544_HPS_FORMAT_FIGEXP M_FIG C_FIG

systems biology↗

bioRxiv2024

Whole genome sequencing of four Ixodes species expands understanding of tick evolution

Ticks, hematophagous acari, pose a significant threat by transmitting various pathogens to their vertebrate hosts during feeding. Despite advances in tick genomics, high-quality genomes were lacking until recently, particularly in the genus Ixodes, which includes the main vectors of Lyme disease. Here, we present the complete genome sequences of four tick species, derived from a single female individual, with a particular focus on the European species Ixodes ricinus, achieving a chromosome-level assembly. Additionally, draft assemblies were generated for the three other Ixodes species, I. persulcatus, I. pacificus and I. hexagonus. The quality of the four genomes and extensive annotation of several important gene families have allowed us to study the evolution of gene repertoires at the level of the genus Ixodes and of the tick group. We have determined gene families that have undergone major amplifications during the evolution of ticks, while an expression atlas obtained for I. ricinus reveals striking patterns of specialization both between and within gene families. Notably, several gene family amplifications are associated with a proliferation of single-exon genes. The integration of our data with existing genomes establishes a solid framework for the study of gene evolution, improving our understanding of tick biology. In addition, our work lays the foundations for applied research and innovative control targeting these organisms.

genomics↗

bioRxiv2017

miRNAgFree: prediction and profiling of novel microRNAs without genome assembly

The prediction of novel miRNA genes generally requires the availability of genome sequences in order to assess important properties such as the characteristic hairpin-shaped secondary structure. However, although the sequencing costs have decreased over the last years, still many important species lack an assembled genome of certain quality. We implemented an algorithm which for the first time exploits characteristic biogenesis features like the 5 homogeneity that can be assessed without genome sequences. We used a phylogenetically broad spectrum of well annotated animal genomes for benchmarking. We found that between 90-100% of the most expressed miRNA candidates (top quartile) corresponded to known miRNA sequences.

bioinformatics↗