Biology subjects

Bapat, S. A.

Publications and source records attributed to Bapat, S. A..

3 recordsLinked to original sources

bioRxiv2025

Evolutionary and functional dynamics of chimeric pseudogenes ({varphi}genes)

Genome-associated changes during evolution followed by selection, facilitate development of new genes, gene families and even species. Pseudogenes ({varphi}genes) generated during such genome rearrangements are often considered "dead on arrival" due to compromised expression arising from disruptive mutations or loss of regulatory elements. In an earlier study, we traced the expression of several {varphi}genes, which challenges this notion. Here, we report segmental duplications at proximal genomic locations occasionally generate chimerism as a continuum of sequences from two or more genes, some of which involve intron fusions. These specific introns and flanking exons are likely to have co-evolved from ancestral parent genes. Notably, co-opting upstream regulatory sequences of 5' parent gene may enable activation of chimeric {varphi}genes, while modifications in 3' sequences impart transcript stability. Few chimeric {varphi}genes also harbor strong coding ORFs to be potentially translated into novel or truncated proteins retaining parental domains. Interestingly, chimeric {varphi}genes are expressed only in human tissues, and display signatures of purifying selection. Examining potential functions associates ANAPC1P2 with genotoxic stress responses, while HYDIN2 may play a putative role in regulating cell cycle progression and neuronal differentiation. Taken together, our results suggest chimeric {varphi}genes and their de novo functions may be relevant to speciation. Significance statementThis study challenges the conventional paradigm that designates pseudogenes ({varphi}genes) as "Dead-On-Arrival" sequences in the genome. Identification of chimeric {varphi}genes formed by segmental duplications involving novel intron fusions highlights their role in evolutionary innovation. Notably, a subset of these chimeric {varphi}genes demonstrates signatures of purifying selective pressure and exhibits exclusive, human-specific expression. More importantly, these {varphi}genes may co-opt regulatory sequences, and contribute to novel gene functions such as genotoxic stress responses, and neuronal differentiation revealing putative mechanisms by which {varphi}genes may foster evolutionary novelty. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=129 SRC="FIGDIR/small/679709v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@4e30b6org.highwire.dtl.DTLVardef@1601166org.highwire.dtl.DTLVardef@1652b5org.highwire.dtl.DTLVardef@1900d05_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2021

Cell geometry distinguishes migration-associated heterogeneity in two-dimensional systems

BackgroundIn vitro migration assays are a cornerstone of cell biology and have found extensive utility in research. Over the past decade, several variations of the two-dimensional (2D) migration assay have improved our understanding of this fundamental process. However, the ability of these approaches to capture the functional heterogeneity during migration and their accessibility to inexperienced users has been limited. MethodsWe downloaded published time-lapse 2D cell migration datasets and subjected them to feature extraction with the Fiji software. We used the Analyze Particles tool to extract ten cell geometry features (CGFs), which were grouped into shape, size and position descriptors. Next, we defined the migratory status of cells using the MTrack2 plugin. All data obtained from Fiji were further subjected to rigorous statistical analysis with R version 4.0.2. ResultsWe observed consistent associative trends between size and shape descriptors and validated the robustness of our observations across four independent datasets. We used these descriptors to resolve the functional heterogeneity during migration by identifying and characterizing non-migrators (NM) and migrators (M). Statistical analysis allowed us to identify considerable heterogeneity in the NM subset, that has not been previously reported. Interestingly, differences in 2D-packing appeared to affect CGF trends and heterogeneity of the migratory subsets for the datasets under investigation. ConclusionWe developed an analytical pipeline using open source tools, to identify and morphologically characterize functional migratory subsets from label-free, time-lapse migration data. Our quantitative approach identified a previously unappreciated heterogeneity of non-migratory cells and predicted the influence of 2D-packing on migration.

cancer biology↗

bioRxiv2018

Functional Balance between TCF21-Slug defines phenotypic plasticity and sub-classes in high-grade serous ovarian cancer

Cellular plasticity and transitional phenotypes add to complexities of cancer metastasis initiated by single cell epithelial to mesenchymal transition or cooperative cell migration (CCM). We identified novel regulatory cross-talks between Tcf21 and Slug in mediating phenotypic and migration plasticity in high-grade serous ovarian adenocarcinoma. Live imaging discerned CCM as being achieved either through rapid cell proliferation or sheet migration. Transitional states were enriched over the rigid epithelial or mesenchymal phenotypes under conditions of environmental stresses. The Tcf21-Slug interplay identified in HGSC tumors through effective stratification of subtypes also contributed to class-switching in response to disease progression or therapy. Our study effectively provides a framework for understanding the relevance of cellular plasticity in situ as a function of two transcription factors.

cancer biology↗