Biology subjects

Zolotarov, G.

Publications and source records attributed to Zolotarov, G..

7 recordsLinked to original sources

bioRxiv2026

Convergent evolution of cluster-wide Hox gene regulation in Bilateria

The anteroposterior collinear expression of Hox genes is a hallmark of animal development that underpins the diversification of body plans1 and life cycles2. However, the origin and drivers of this coordinated expression remain elusive: while vertebrates rely on complex cluster-wide Hox gene regulation3-8, insects define gene-specific, sub-cluster regulatory domains9-11. Here, we discover a new mode of Hox gene regulation in segmented worms (Annelida). By combining chromatin conformation data with histone modifications profiling in Owenia fusiformis, we show that a large distal enhancer forms developmentally regulated, long-range contacts across the Hox cluster, and its activation coincides with the consolidation of a cluster-wide topologically associating domain (TAD), loss of Polycomb-mediated repression, and Hox gene transcription. This chromatin structure also occurs in the annelids Dimorphilus gyrociliatus and Capitella teleta, the latter showing additional subTAD structures that correlate with Hoxs temporal collinearity12. Moreover, related phyla with intact, organised Hox clusters and spatial collinearity, such as nemerteans and chitons, show annelid-like chromatin organisations, whereas phyla with disorganised13 Hox clusters do not. Coordinated Hox gene regulation from a "global control region" is thus ancestral to Lophotrochozoa, indicating that complex regulatory logics based on cluster-wide, long-range chromatin interactions with distal enhancers evolved convergently in vertebrates and spiralians.

developmental biology↗

bioRxiv2025

Decoding cnidarian cell type gene regulation

Animal cell types are defined by differential access to genomic information, a process orchestrated by the combinatorial activity of transcription factors that bind to cis-regulatory elements (CREs) to control gene expression. However, the regulatory logic and specific gene networks that define cell identities remain poorly resolved across the animal tree of life. As early-branching metazoans, cnidarians can offer insights into the early evolution of cell type-specific genome regulation. Here, we profiled chromatin accessibility in 60,000 cells from whole adults and gastrula-stage embryos of the sea anemone Nematostella vectensis. We identified 112,728 CREs and quantified their activity across cell types, revealing pervasive combinatorial enhancer usage and distinct promoter architectures. To decode the underlying regulatory grammar, we trained sequence-based models predicting CRE accessibility and used these models to infer ontogenetic relationships among cell types. By integrating sequence motifs, transcription factor expression, and CRE accessibility, we systematically reconstructed the gene regulatory networks that define cnidarian cell types. Our results reveal the regulatory complexity underlying cell differentiation in a morphologically simple animal and highlight conserved principles in animal gene regulation. This work provides a foundation for comparative regulatory genomics to understand the evolutionary emergence of animal cell type diversity.

genomics↗

bioRxiv2024

Capturing changes to animal complexity from quantifiable patterns in genomic data

A prevailing problem in evolutionary biology is elucidating the "genotype-phenotype map" that characterizes how genomic activities regulate different aspects of organismal morphology and their variability in both space and time. Here, we explore potential causality between genome content and both morphological complexity and disparity by compiling the regulatory components (i.e., transcription factors, RNA binding proteins, and microRNA families) as well as a representative set of non-regulatory "housekeeping genes" in 32 species belonging to a wide variety of animal phyla, altogether encapsulating a number of varying genomic characteristics and morphological diversities. A principal component analysis of these four non-overlapping genomic components from each of these 32 species in relation to their last common ancestor revealed that no relationship exists between genome space and disparity, as changes to animal body plans appear to be largely the result of changes to the gene regulatory networks that govern animal development rather than gaining or losing specific sets of regulatory genes. However, using both phylogenetically correlated as well as phylogenetically uncorrelated statistical tests, we find a strong relationship between the loss of all considered gene types and the advent of some parasitic taxa, as well as between microRNA innovations and organismal complexity. While this analysis of genomic features suggests how complexity and disparity are each encoded in the genome, further analysis of the regulatory networks in which they participate should provide a more comprehensive description of how organisms diversify their morphologies over time through alterations in their genomic components. SIGNIFICANCE STATEMENTVariation in morphological form can be measured by considering either disparity (i.e., the amount of variance in morphological form) or complexity (i.e., the difference in the number of their "parts" including genes or cells). To date, discerning the genomic basis of either has remained largely unknown. Here, we compile the regulatory genome of the last common ancestor of bilaterian metazoans, including its transcription factors, RNA-binding proteins and microRNA families, and ask how changes to these repertoires potentially reflects changes in either disparity or complexity. We find that although there is no relationship between the regulatory genome and disparity, there is a robust relationship between the loss of regulatory genes relative to housekeeping genes, especially in parasitic taxa. Further, there is a strong relationship between increases to microRNAs and complexity, which likely reflects the unique role microRNAs play in increasing both the accuracy and the precision of gene expression during development.

evolutionary biology↗

bioRxiv2023

GeneExt: a gene model extension tool for enhanced single-cell RNA-seq analysis

Incomplete gene models negatively impact single-cell gene expression quantification. This is particularly true in non-model species where often gene 3' ends are inaccurately annotated, while most scRNA-seq methods only capture the 3' transcript region. This results in many genes being incorrectly quantified or not detected. GeneExt leverages scRNA-seq data to refine gene annotations, enhancing biological interpretation and cross-species comparisons of cell type expression atlases.

bioinformatics↗

bioRxiv2023

miR-7 controls glutamatergic transmission and neuronal connectivity in a Cdr1as-dependent manner

The circular RNA (circRNA) Cdr1as is conserved across mammals and highly expressed in neurons, where it directly interacts with microRNA miR-7. However, the biological function of this interaction is unknown. Here, using primary forebrain murine neurons, we demonstrate that stimulating neurons by sustained depolarization rapidly induced two-fold transcriptional up-regulation of Cdr1as and strong post-transcriptional stabilization of miR-7. Cdr1as loss caused doubling of glutamate release from stimulated synapses and increased frequency and duration of local neuronal bursts. Moreover, periodicity of neuronal networks was increased and synchronicity was impaired. Strikingly, these effects were reverted by sustained expression of miR-7 which also cleared Cdr1as molecules from neuronal projections. Consistently, without Cdr1as, transcriptomic changes caused by miR-7 overexpression were stronger (including miR-7-targets down-regulation) and enriched in secretion/synaptic plasticity pathways. Altogether, our results suggest that in forebrain neurons Cdr1as buffers miR-7 activity to control glutamatergic excitatory transmission and neuronal connectivity important for long-lasting synaptic adaptations.

molecular biology↗

bioRxiv2022

MicroRNAs are deeply linked to the emergence of the complex octopus brain

Soft-bodied cephalopods such as the octopus are exceptionally intelligent invertebrates with a highly complex nervous system that evolved independently from vertebrates. Because of elevated RNA editing in their nervous tissues, we hypothesized that RNA regulation may play a major role in the cognitive success of this group. We thus profiled mRNAs and small RNAs in 18 tissues of the common octopus. We show that the major RNA innovation of soft-bodied cephalopods is a massive expansion of the miRNA gene repertoire. These novel miRNAs were primarily expressed in neuronal tissues, during development, and had conserved and thus likely functional target sites. The only comparable miRNA expansions happened, strikingly, in vertebrates. Thus, we propose that miRNAs are intimately linked to the evolution of complex animal brains. One-Sentence SummarymiRNAs are deeply linked to the emergence of complex brains.

evolutionary biology↗

bioRxiv2022

Cell type diversity in a developing octopus brain

Octopuses are mollusks that have evolved intricate neural systems comparable with vertebrates in terms of cell number, complexity and size. The cell types within the octopus brain that control their amazingly rich behavioral repertoire are still unknown. Here we profile cell diversity of the paralarval Octopus vulgaris brain to build a comprehensive cell type atlas that comprises mostly neural cells, as well as multiple glial subtypes, endothelial cells and fibroblasts. Moreover, we spatially map cell types within the octopus brain, including vertical and optic lobe cell types. Investigation of cell type conservation reveals a shared gene signature between glial cells of mice, fly and octopus. Genes related to learning and memory are enriched in vertical lobe cells, which show molecular similarities with Kenyon cells in Drosophila. Taken together, our data sheds light on cell type diversity and evolution of the complex octopus brain. Highlights & Key findingsO_LICharacterization of different cell types present in the early paralarval brain C_LIO_LICross-species comparisons reveal a conserved glial gene expression signature C_LIO_LIVertical lobe amacrine cells in octopus have molecular similarities to fly Kenyon cells C_LIO_LIHomeobox genes are defining transcription factors for cell type identity C_LIO_LIRecently expanded gene families may underlie cellular diversification C_LI

developmental biology↗