Biology subjects

Sharma, S. P.

Publications and source records attributed to Sharma, S. P..

6 recordsLinked to original sources

bioRxiv2026

Recurrent Duplication of the REST-NOA1 Locus Reveals a Hotspot of Regulatory Evolution Across Even-Toed Ungulates

Gene duplication is a major source of evolutionary novelty, yet recurrent duplication of the same genomic locus across independent lineages remains understudied. Using a chromosome-scale assembly and de novo annotation of the North American bison (Bison bison), we investigated the mechanisms underlying immune-system diversification in ungulates. Comparative genomics of bison, cattle, elk, and 13 mammalian species identified a large segmental duplication encompassing the regulatory genes REST and NOA1. Although similar duplications were present in 14/16 species examined, phylogenetic analyses revealed that duplicated genes cluster within species rather than across taxa, indicating repeated independent origins rather inheritance from a common ancestor. To characterize the evolutionary consequences of this duplication, we integrated transcriptomics from six tissues with weighted gene co-expression and comparative protein clustering. We identified extensive structural divergence among duplicated copies of REST and NOA1, including domain losses, truncations, and expression partitioning across tissues, consistent with functional divergence following duplication. Comparative analyses revealed substantial remodeling of immune-related genes in bison, including BOLA class I molecules, T-cell receptor genes, leukocyte immunoglobulin-like receptors, and regulators of immune signaling. These modifications included domain rearrangements, novel sequence insertions, and lineage-specific duplications associated with immune-related expression networks. Together, these findings identify the REST-NOA1 locus as a recurrent hotspot of segmental duplication in ungulates and demonstrate how repeated duplication, structural divergence, and regulatory partitioning contribute to genome evolution. These results suggest that immune system diversification in bison and related species has been shaped not only by sequence evolution but also by recurrent remodeling of regulatory pathways and antigen-recognition pathways.

bioinformatics↗

bioRxiv2023

An ensemble of Gleditsia sinensis Lam. and gut microbiota against alcoholic liver disease

Gleditsia sinensis Lam. (GSL) is a medicinal herb and a noticeable resource of possessing hepatic protective agents such as alcoholic liver disease (ALD). At present, it has been documented that gut microbiota (GM) is related directly to etiology of ALD. Nevertheless, the bioactive molecules in GSL, favorable GM, targets, and key mechanism(s) against ALD are yet to be revealed. Hence, we integrated the significant four components to clarify the nuanced pathogenesis with help of network pharmacology (NP) concept. We retrieved significant metabolites via gutMGene and constructed GSL or GM-Signaling pathways-Targets-Metabolites (GGSTM) networks. Finally, molecular docking test (MDT) was performed to verify the key findings. The gutMGene suggested that 16 GM and 6 metabolites were related to the two signaling pathways through GGSTM networks. Both MDT and frontier molecular orbitals (FMO) theory revealed the most stable conformers: equol from Lactobacillus paracasei JS1 on IL6, Bauer-7-en-3-one, and Urs-12-en-3-one from GSL on PPARA, PPARD, and PPARG, respectively. In conclusion, this study sheds light on the combinatorial effects of GM, and GSL in treating ALD via systems biology concept.

systems biology↗

bioRxiv2023

Damage-induced senescent immune cells regulate regeneration of the zebrafish retina

Zebrafish spontaneously regenerate their retina in response to damage through the action of Muller glia. Even though Muller glia (MG) are conserved in higher vertebrates, the capacity to regenerate retinal damage is lost. Recent work has focused on the regulation of inflammation during tissue regeneration with precise temporal roles for macrophages and microglia. Senescent cells that have withdrawn from the cell cycle have mostly been implicated in aging, but are still metabolically active, releasing pro-inflammatory signaling molecules as part of the Senescence Associated Secretory Phenotype (SASP). Here, we discover that in response to retinal damage, a subset of cells expressing markers of microglia/macrophages also express markers of senescence. These cells display a temporal pattern of appearance and clearance during retina regeneration. Premature removal of senescent cells by senolytic treatment led to a decrease in proliferation and incomplete repair of the ganglion cell layer after NMDA damage. Our results demonstrate a role for modulation of senescent cell responses to balance inflammation, regeneration, plasticity, and repair as opposed to fibrosis and scarring.

cell biology↗

bioRxiv2022

Complex chromosomal rearrangements induced by transposons in maize

Eukaryotic genomes are large and complex, and gene expression can be affected by multiple regulatory elements and their positions within the dynamic chromatin architecture. Transposable Elements (TEs) are known to play important roles in genome evolution, yet questions remain as to how TEs alter genome structure and affect gene expression. Previous studies have shown that genome rearrangements can be induced by Reversed Ends Transposition (RET) involving termini of Activator (Ac) and related TEs in maize and other plants. Here, we show that complex alleles can be formed by the rapid and progressive accumulation of Ac-induced duplications and rearrangements. The p1 gene enhancer in maize can induce ectopic expression of the nearby p2 gene in pericarp tissue when placed near it via different structural rearrangements. By screening for p2 expression, we identified and studied five cases in which multiple sequential transposition events occurred and increased the p1 enhancer copy number. We see active p2 expression due to multiple copies of the p1 enhancer present near p2 in all five cases. The p1 enhancer effects are confirmed by the observation that loss of p2 expression is correlated with transposition-induced excision of the p1 enhancers. We also performed a targeted Chromosome Conformation Capture (3C) experiment to test the physical interaction between the p1 enhancer and p2 promoter region. Together, our results show that transposon-induced rearrangements can accumulate rapidly, and progressively increase genetic variation important for genomic evolution.

genetics↗

bioRxiv2021

Transposon-induced inversions activate gene expression in Maize pericarp

Chromosomal inversions can have considerable biological and agronomic impacts including disrupted gene function, change in gene expression and inhibited recombination. Here we describe the molecular structure and functional impact of six inversions caused by Alternative Transpositions between p1 and p2 genes responsible for floral pigmentation in maize. In maize line p1-wwB54, the p2 gene is expressed in anther and silk but not in pericarp, making the kernels white. We identified inversions in this region caused by transposition of Ac and fractured Ac (fAc) transposable elements. These inversions change the position of a p1 enhancer and activate the expression of p2 in the kernel pericarp, resulting in red kernel color. We hypothesize that these inversions place the p2 gene promoter near a p1 gene enhancer, thereby activating p2 expression in kernel pericarp.

genetics↗

bioRxiv2020

Anti-microbial activity of potential probiotic lactic acid bacteria against Methicillin-Resistant Staphylococcus Aureus (MRSA)

Lactic acid bacteria (LAB)are the essential ingredients in probiotic foods, intestinal microflora, and dairy products able to cope up and exist in diverse environmental ranges. Samples were collected using sterile test tubes and transported to a laboratory in the icebox for further biochemical characterization. Gram test and catalase activity were examined after microscopically distinct colonies were sub-cultured to pure colonies based on standard gram and catalase test protocols. Subsequently, these bacteria were characterized for their ability to grow at various salt concentrations (5%,10%, and15%) and temperature gradients (15{degrees}C, 30{degrees}C, 45{degrees}C). Acid-tolerance was analyzed by growing the colonies in MRS broth adjusted to acidic pH (pH 3) and pH 7.2 (control). Bile tolerance of LAB isolates was assayed by growing in 0.3% bile-supplemented MRS agar. Bile salt hydrolase (BSH) activity was studied by growing 10 l of the prepared overnight culture on BSH screening media containing MRS agar plate supplemented with bile salts. The LAB isolates were checked for antimicrobial activity by agar well diffusion assay. All isolates found gram-positive, catalase-negative and non-motile, convex elevation and entire margin. All LAB isolates were able to grow at 5-10% Nacl concentration, whereas moderately grow at 10% concentration but rarely grow at 15% Nacl concentration. BCM2, BBM3 and BGM1 record the highest acidic resistance viability percentage 94.9%, 92.7%, and 91.8% respectively. BCM3 has the lowest acidic resistance with a viable percentage of 87.4%. BBM1 records the highest bile tolerance activity whereas BCM2 has the lowest bile tolerance. All isolates were found BSH positive. The study reveals LAB isolates showed a putative probiotic potential. Article highlightsLAB are the main ingredients of probiotic products commercially available in the market nowadays. To effectively functioning the host gastrointestinal tract probiotics, need to have certain criteria like acid and bile tolerance this study reveals O_LIAcid tolerance activity of LAB isolated from bovine milk C_LIO_LIBile tolerance activity of LAB isolated from bovine milk C_LIO_LIBile salt hydrolase (BSH) activity of LAB isolates C_LIO_LIAntimicrobial activity of LAB against MRSA C_LI

microbiology↗