Biology subjects

Arkhipova, K.

Publications and source records attributed to Arkhipova, K..

6 recordsLinked to original sources

bioRxiv2024

Phylogenetic Study of Long Non-Coding RNA NEAT1 and MALAT1 to Infer Structural-Functional Connection

NEAT1 and MALAT1 are the only two lncRNAs that utilise the tRNA-processing machinery for their maturation, coded very close to each other yet differing in function and evolutionary conservation. Here, we identified NEAT1 and MALAT1 orthologs in 545 mammals and studied their conservation patterns to gain functional insights. In the functional basis of NEAT1Long, we found G-quadruplexes and short sequence motifs that interact with the DSHS family of proteins and TDP-43, as well as gene length and self-complementary regions that further stabilise paraspeckle integrity. We found that transposable elements play a crucial role in NEAT1 evolution by contributing structures recognised by DSHS proteins. We identified the NEAT1Short isoform in all NEAT1 orthologs, and our results suggest its distinct functional role. Our findings also support the conservation of the isoform switch mechanism mediated by TDP-43. The function of MALAT1 is likely based on its highly conserved primary sequence, and we demonstrated the gene regions under stronger purifying selection. This is the first large-scale phylogenetic study of NEAT1 - a lncRNAs that lack sequence similarity between orthologs while maintaining functional and syntenic conservation.

evolutionary biology↗

bioRxiv2024

Capture of Human Neuromesodermal and Posterior Neural Tube Axial Stem Cells

The spinal cord, nerves, and skeletal muscles arise from neuromesodermal progenitors (NMPs). We have developed a growth-factor screening strategy, utilizing ES and iPS cells, facilitating the indefinite self-renewal of two types of human axial stem cells (AxSCs), closely resembling mouse NMPs (NM-AxSCs) and posterior neural tube progenitors (N-AxSCs). Under specific regimens-- Wnt/CHIR99021, FGF2, and TGF-{beta} inhibitor SB431542 (CFS) and excluding FGF2 (CS), respectively--these AxSCs self-renew and sustain telomeres. Single cell transcriptomics and proteomics have revealed expression of posterior growth-zone and dorsoventral neural tube markers in NM-AxSCs, and correspondingly, differentiation to a wide spectrum of neural tube neurons and myocytes. N-AxSCs rapidly matured into dorsal sensory subsets and neural crest. Crucially, neither AxSC type produces teratomas, and analogous mouse NM-AxSCs integrated successfully into the neural tube and somites. Capturing of AxSCs from patient and GMP ES / iPS cells without transgenesis unveils ontogeny and promises modeling and therapy in neuropathies.

developmental biology↗

bioRxiv2021

High viral abundance and low diversity are associated with increased CRISPR-Cas prevalence across microbial ecosystems

CRISPR-Cas are adaptive immune systems that protect their hosts against viruses and other parasitic mobile genetic elements. Consequently, selection from viruses and other genetic parasites is often assumed to drive the acquisition and maintenance of these immune systems in nature, but this remains untested. Here, we analyse the abundance of CRISPR arrays in natural environments using metagenomic datasets from 332 terrestrial, aquatic and host-associated ecosystems. For each metagenome we quantified viral abundance and levels of viral community diversity to test whether these variables can explain variation in CRISPR-Cas abundance across ecosystems. We find a strong positive correlation between CRISPR-Cas abundance and viral abundance. In addition, when controlling for differences in viral abundance, we found that the CRISPR-Cas systems are more abundant when viral diversity is low. We also found differences in relative CRISPR-Cas abundance among environments, with environmental classification explaining [~]24% of variation in CRISPR-Cas abundance. However, the correlations with viral abundance and diversity are broadly consistent across diverse natural environments. These results indicate that viral abundance and diversity are major ecological factors that drive the selection and maintenance of CRISPR-Cas in microbial ecosystems. Significance statementNumerous studies demonstrate that CRISPR-Cas immune systems can provide defence against bacteriophage and archaeal viruses, yet little is known about the ecological conditions where CRISPR-Cas immunity is favoured. Moreover, our knowledge is largely confined to laboratory studies and it is unknown if viruses are a key selective driver of CRISPR-Cas in nature. Using metagenomic data from diverse environments we find that both viral abundance and the abundance of CRISPR-Cas immune systems correlate positively across most environments. Furthermore, CRISPR-Cas systems are more prevalent when viral diversity is low. These results extend previous theoretical work by demonstrating that viruses are a key driver of selection of CRISPR-Cas immune systems across many natural ecosystems.

microbiology↗

bioRxiv2020

Long identical sequences found in multiple bacterial genomes reveal frequent and widespread exchange of genetic material between distant species.

Horizontal transfer of genomic elements is an essential force that shapes microbial genome evolution. Horizontal Gene Transfer (HGT) occurs via various mechanisms and has been studied in detail for a variety of systems. However, a coarse-grained, global picture of HGT in the microbial world is still missing. One reason is the difficulty to process large amounts of genomic microbial data to find and characterise HGT events, especially for highly distant organisms. Here, we exploit the fact that HGT between distant species creates long identical DNA sequences in genomes of distant species, which can be found efficiently using alignment-free methods. We analysed over 90 000 bacterial genomes and thus identified over 100 000 events of HGT. We further developed a mathematical model to analyse the statistical properties of those long exact matches and thus estimate the transfer rate between any pair of taxa. Our results demonstrate that long-distance gene exchange (across phyla) is very frequent, as more than 8% of the bacterial genomes analysed have been involved in at least one such event. Finally, we confirm that the function of the transferred sequences strongly impact the transfer rate, as we observe a 3.5 order of magnitude variation between the most and the least transferred categories. Overall, we provide a unique view of horizontal transfer across the bacterial tree of life, illuminating a fundamental process driving bacterial evolution.

bioinformatics↗

bioRxiv2019

A symbiont phage protein aids in eukaryote immune evasion

Phages are increasingly recognized as important members of host associated microbial communities. While recent studies have revealed vast genomic diversity in the virosphere, the new frontier is to understand how newly discovered phages may affect higher order processes, such as in the context of host-microbe interactions. Here, we aim to understand the tripartite interplay between phages, bacterial symbionts and marine sponges. In a viromics approach, we discover 491 novel viral clusters and show that sponges, as filter-feeding organisms, are distinct viral niches. By using a nested sampling design, we show that each sponge individual of the four species investigated harbours its own unique virome, regardless of the tissue investigated. We further discover a novel, symbiont phage-encoded ankyrin domain-containing protein which appears to be widely spread in phages of many host-associated contexts including human. The ankyrin protein (ANKp) modulates the eukaryotic immune response against bacteria as confirmed in macrophage infection assays. We predict that the role of ANKp in nature is to facilitate co-existence in the tripartite interplay between phages, symbionts and sponges and possibly in many other host-microbe associations.

microbiology↗

bioRxiv2019

Robust taxonomic classification of uncharted microbial sequences and bins with CAT and BAT

Current-day metagenomics increasingly requires taxonomic classification of long DNA sequences and metagenome-assembled genomes (MAGs) of unknown microorganisms. We show that the standard best-hit approach often leads to classifications that are too specific. We present tools to classify high-quality metagenomic contigs (Contig Annotation Tool, CAT) and MAGs (Bin Annotation Tool, BAT) and thoroughly benchmark them with simulated metagenomic sequences that are classified against a reference database where related sequences are increasingly removed, thereby simulating increasingly unknown queries. We find that the query sequences are correctly classified at low taxonomic ranks if closely related organisms are present in the reference database, while classifications are made higher in the taxonomy when closely related organisms are absent, thus avoiding spurious classification specificity. In a real-world challenge, we apply BAT to over 900 MAGs from a recent rumen metagenomics study and classified 97% consistently with prior phylogeny-based classifications, but in a fully automated fashion.

bioinformatics↗