Biology subjects

Gelfand, M.

Publications and source records attributed to Gelfand, M..

6 recordsLinked to original sources

bioRxiv2026

Short gene overlaps in bacterial genomes: evolutionary dynamics and functional associations

Short overlaps of adjacent genes are widespread in bacterial genomes and have been proposed to contribute to coordinated gene expression through mechanisms such as translational coupling and ribosome re-initiation. However, their evolutionary dynamics and functional associations have been studied either in relatively small datasets or for individual taxonomic groups. Here, we performed a large-scale comparative analysis of bacterial gene overlaps to characterize their prevalence, structural diversity, evolutionary dynamics, and functional associations. We surveyed 3,998 representative bacterial genomes for short overlaps and analyzed a curated set of orthologous gene-pair clusters to reconstruct the evolutionary history of overlap gain and loss using ancestral-state inference. We confirmed that short overlaps are dominated by a small number of canonical configurations, while a substantial subset of orthologous clusters contained multiple overlap lengths or sequence motifs, indicating evolutionary flexibility. Reconstruction of ancestral states yielded repeated gains and losses of overlap within the same orthologous gene-pair lineages. Among clusters in which both states were sufficiently represented, we found no overall bias toward either overlap gain or loss. Finally, analyses of functional associations found no consistent enrichment of overlapping gene pairs among genes encoding interacting protein subunits, compared to closely spaced non-overlapping gene pairs. In contrast, metabolic linkage showed a modest positive association with overlap, although the magnitude of this association depended on the distance threshold used to define non-overlapping neighbors. These results identify short bacterial gene overlaps as evolutionarily labile features of gene organization rather than strongly conserved genomic states and emphasize the importance of distinguishing overlap from close genomic proximity when considering their functional significance.

evolutionary biology↗

bioRxiv2025

Conservation of non-consensus nucleotides in transcription factor binding sites

Transcription factors (TFs) affect gene expression by binding to their sites (TFBSs) in the genome. As regulation of transcription is essential for the optimization of metabolism, evolution of TFBSs is thought to be restricted by the TF binding preferences. This means that nucleotides important for binding (consensus nucleotides, CNs) experience the pressure of negative selection and, therefore, are highly conserved. However, for some regulated genes, the strongest possible repression or activation may not necessarily be optimal (i.e. provide the highest fitness). Here, we show that, along with CNs, nucleotides causing relatively weaker binding (non-consensus nucleotides, NCNs) are sometimes preserved by negative selection. We then consider several possible reasons for the conservation of NCNs and demonstrate that NCNs depend epistatically on other loci of the same TFBS for a substantial fraction of TFBSs.

bioinformatics↗

bioRxiv2024

Deciphering the 3D genome organization across species from Hi-C data

Three-dimensional genome organization is essential for gene regulation, yet in various species it is driven by different biological mechanisms. Species-specific factors and DNA sequences influence chromatin folding, complicating cross-species comparisons. Leveraging Hi-C data and machine learning, we introduce Chimaera -- a convolutional neural network that predicts Hi-C maps from DNA sequences, enabling exploration of genome folding in evolution. Chimaeras latent representations revealed an unsupervised atlas of key chromatin features (such as insulation, loops, fountains/jets) and supported the detection and quantification of structural signatures in processes such as the cell cycle and embryogenesis. Targeted search in the latent space linked DNA sequence elements to specific chromatin structures. Applying Chimaera across multiple species confirmed the insulator roles of CTCF in vertebrates and BEAF-32 in D. melanogaster and identified a previously unreported insulator motif in D. melanogaster. In amoeba D. discoideum, gene orientation on the DNA strand was shown to influence loop formation. Models for other organisms also showed chromatin folding patterns associated with gene location. Finally, using cross-species predictions we tested the transferability of chromatin folding patterns and revealed evolutionary relationships, culminating in a chromatin structure-based cluster tree spanning plants to mammals. GRAPHICAL ABSTRACT O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=81 SRC="FIGDIR/small/623548v3_ufig1.gif" ALT="Figure 1"> View larger version (34K): org.highwire.dtl.DTLVardef@cb8560org.highwire.dtl.DTLVardef@1a17899org.highwire.dtl.DTLVardef@1f4b8eforg.highwire.dtl.DTLVardef@19979de_HPS_FORMAT_FIGEXP M_FIG C_FIG

bioinformatics↗

bioRxiv2023

optimalTAD: annotation of topologically associating domains based on chromatin marks enrichment

In many eukaryotes, chromosomes are organized as strings of spatially segregated Topologically Associating Domains (TADs), characterized by a substantially increased frequency of interactions within them. Boundaries of TADs are highly enriched in histone acetylation chromatin marks and occupied binding sites of architectural proteins, highlighting the functional role of TADs in the regulation of gene expression. While many computational approaches have been developed for TAD identification, it remains challenging because of their nested structure, resulting in weakly overlapping sets of TADs at different scales. Here, we propose a novel algorithm optimalTAD for identifying the optimal set of TADs based on epigenetic marks enrichment. Assuming that the most dramatic enrichment corresponds to the best annotation of TAD boundaries, our algorithm optimizes TAD calling parameters by maximizing the difference in chromatin mark levels between TADs and their boundaries. Using this algorithm, we annotated TADs in multiple publicly available fruit fly and mammalian Hi-C datasets and identified a set of epigenetic marks that are best suited for TAD prediction. Through the analysis of diverse organisms and cell types with distinct underlying principles of TAD organization, we have shown that optimalTAD is a universal tool suitable for studying TAD structure, functions, and properties unique to specific cell types and organisms. optimalTAD is freely available at GitHub: https://github.com/cosmoskaluga/optimalTAD. Key PointsO_LIWe assume that the most dramatic enrichment of epigenetic marks corresponds to the best annotation of TAD boundaries. C_LIO_LIOur algorithm optimizes TAD calling parameters by maximizing the difference in chromatin mark levels between TADs and their boundaries. C_LIO_LIoptimalTAD is a universal tool that is applicable for studying TAD characteristics in diverse organisms and cell types. C_LIO_LIoptimalTAD enables the identification of a specific set of epigenetic marks that are most suitable for annotating TADs. C_LI

bioinformatics↗

bioRxiv2021

A hierarchy in clusters of cephalopod mRNA editing sites

RNA editing in the form of substituting adenine to inosine (A-to-I editing) is the most frequent type of RNA editing, observed in many metazoan species. A-to-I editing sites form clusters in most studied species, and editing at clustered sites depends on editing of the adjacent sites. Although functionally important in some specific cases, A-to-I editing in most considered species is rare, the exception being soft-bodied cephalopods (coleoids), where tens of thousands of potentially important A-to-I editing sites have been identified, making coleoids an ideal object for studying of general properties and evolution of A-to-I editing sites. Here, we apply several diverse techniques to demonstrate a strong tendency of coleoid RNA editing sites to cluster along the transcript. We identify three distinct types of editing site clusters, varying in size, and describe RNA structural features and mechanisms likely underlying formation of these clusters. In particular, these observations may resolve the paradox of sequence conservation at large distances around editing sites.

bioinformatics↗

bioRxiv2020

New intranuclear symbiotic bacteria from macronucleus of Paramecium putrinum -- Candidatus Gortzia yakutica

Holospora-like bacteria are obligate intracellular Alphaproteobacteria, inhabiting nuclei of Paramecium ciliates and other protists. Alphaproteobacteria have drawn significant attention, as both closest existing relatives of bacteria that gave rise to mitochondria, as well as a class of intracellular bacteria with numerous important pathogens. HLB clade includes two genera - Holospora (Hafkine 1980) and candidatus Gortzia (Boscaro 2013). These bacteria have a peculiar life cycle with two morphological forms, a strict specificity to the host species and the type of nucleus they inhabit. Here we describe a new species of HLB - candidatus Gortzia yakutica sp. nov., a symbiont from macronucleus of Paramecium putrinum, the first known HLB for this Paramecium species. The new symbiont shows morphological similarities with other HLB. The phylogenetic analysis of SSU rDNA gene places it into candidatus Gortzia clade.

microbiology↗