Biology subjects

Dwivedi, M.

Publications and source records attributed to Dwivedi, M..

7 recordsLinked to original sources

bioRxiv2026

WGT-aware analysis reveals increased complexity in the yohimbane biosynthesis pathway of Rauvolfia tetraphylla

Arising from Stander et al. Communications Biology https://doi.org/10.1038/s42003-023-05574-8 (2023) Rauvolfia tetraphylla (Apocynaceae), distributed across Mexico, Tropical America, and Southeast Asia, is known to produce pharmacologically important monoterpene indole alkaloids such as ajmaline, reserpiline, yohimbine, and heteroyohimbanes1. Elucidating the enzymatic pathways2 underlying their biosynthesis is therefore essential for enhancing our understanding of MIA metabolism and enabling their industrial production. In a recent edition of Communication Biology, Stander et al. [STAN23]3 presented a high-quality assembly for R. tetraphylla and uncovered the yohimbane biosynthesis pathway. Based on their proteomics and transcriptomic analysis, two major findings emerged: (1) a medium chain dehydrogenase/reductase (MDR), yohimbane synthase (YOS), produces four yohimbane diastereomers, and (2) three MDR transcripts (MDRT), MSTRG.5530, MSTRG.5531, and MSTRG.5534, along with geissoschizine synthase (GS, MSTRG.5528), can generate a mixture of yohimbane isomers. However, our reanalysis of the raw sequencing reads incorporating haplotype phasing and expression profiling revealed that most candidate genes exist as three homeologous copies with distinct tissue-specific expression. Furthermore, we demonstrate preferential interactions among specific MDRT and GS homeologs, indicating complex cross-subchromosomal enzymatic organisation overlooked in STAN23. Furthermore, several reported candidate genes are chimeric, indicating that incorrect estimation of whole-genome triplication and lack of haplotype phasing can severely limit robust identification and functional characterisation of the yohimbane biosynthetic pathway.

genomics↗

bioRxiv2025

Sequence Complexity Dictates Polymer Mixing

Polymer association in confined spaces governs diverse phenomena from protein aggregation to DNA condensation. We investigate the sequence-level mechanisms underlying this behavior through exact enumeration of two confined AB-type block copolymers on a two-dimensional lattice, revealing how sequence complexity controls mixing against de-mixing. We reveal that sequence complexity (heterogeneity), quantified by Shannon entropy H2, acts as a determinant between self-folded low-mixed state and high-mixed state. High-complexity sequences (H2 = 1.86 bits) with short-length repeats achieve near-complete inter-chain overlap through cooperative chain collapse, while low-complexity blocky sequences (H2 = 1.26 bits) maintain extended conformations with less overlapping. Free energy analysis reveals a steep increase in mixing barriers for low-complexity compared to surmountable barrier for high-complexity sequences. We find that geometric confinement modulates but does not override these sequence-dependent behaviors, with asymmetric confinement enhancing heterogeneity in overlapping for both sequence type (pronounced in high-H2 sequences). Our theory could be applicable in assessing the phase behavior of repeat protein and nucleic acid sequences.

biophysics↗

bioRxiv2025

De novo genome Assembly of Rauvolfia Serpentina and comparative paleodemographic analysis of Apocynaceae plants

Rauvolfia serpentina is a perennial subshrub widely distributed across Asia and the Indian subcontinent. Belonging to the medicinally important Apocynaceae family, it is renowned for its ecological importance and ethnobotanical applications, especially through the biosynthesis of therapeutic indole alkaloids. In this study, we present a de novo genome assembly and annotation for R. serpentina. The assembled genome comprises approximately 184,000 scaffolds with a scaffold N50 of 7.18 Kbp and a high BUSCO completeness score of [~]90% encompassing [~]22,000 annotated genes. We analysed the paleodemographic histories of nine additional Apocynaceae species using Pairwise Sequentially Markovian Coalescent (PSMC) modelling to place these findings in a broader evolutionary context. This comparative analysis revealed a consistent signature of a pronounced bottleneck across the family during the Mid-Pleistocene glaciations, with few notable species showing high adaptive resilience marked by early recovery in effective population size (Ne), while some even showed secondary Ne peaks in the warmer interglacial periods. Although marked by complex and fairly distinct demographic trajectories, most species exhibit stabilised Ne near the onset of the Holocene. The availability of this high-quality draft genome assembly provides an important resource to advance functional, ecological, and comparative genomics in R. serpentina as well as aid heterologous production of pharmaceutically important biomolecules at an industrial scale, thereby alleviating the pressure on wild populations.

evolutionary biology↗

bioRxiv2025

Melatonin and GABA monotherapies are as efficacious as combination therapy in managing T1D and T2D: In-vivo studies on experimental diabetic models

BackgroundLoss of functional {beta}-cell mass is a critical factor in the ontogenesis of type 1 (T1D) and type 2 diabetes (T2D) marked by chronic hyperglycemia. Melatonin (M) and {gamma}-aminobutyric acid (GABA/G) have immunoregulatory properties and have shown potential to increase {beta}-cell mass in experimental diabetic models. Thus, we aimed to investigate the therapeutic potential of melatonin combined with GABA on {beta}-cell regeneration in streptozotocin (STZ)-induced T1D and on a high-fat diet (HFD)-induced T2D mouse models. MethodsThe BALB/c mice were injected with 50 mg/kg body weight STZ on five consecutive days to induce T1D and were subjected to six weeks of monotherapy with melatonin or GABA and combination therapy (M+G). HFD was fed to C57BL/6J mice for 30 weeks to induce insulin resistance and T2D, followed by six weeks of mono or combination therapy exposure. ResultsOur studies on monotherapies and combination therapy reduced fasting blood glucose levels, increased plasma insulin levels and glucose tolerance, and promoted {beta}-cell proliferation and transdifferentiation, with a simultaneous decrease in {beta}-cell apoptosis in T1D mice. It also improved metabolic parameters and glycolipid metabolism in the liver and adipose tissue, respectively, and increased mitochondrial function in the skeletal muscle. Moreover, it restored peripheral insulin sensitivity and {beta}-cell mass in T2D mice. ConclusionOur studies suggest that monotherapies are as effective as combination therapy since melatonin and GABA sub-additively ameliorates T1D and T2D manifestations.

biochemistry↗

bioRxiv2024

Heterogeneity induced Block Copolymer Segregation in Confinement

Motivated by the work on block copolymer models that provide insights into epigenetics driven chromosome organization, we investigate the segregation behavior of five distinct 2-block co-polymers (BCPs) system with varying block sizes, confined within both symmetric and lateral geometries. Using exact enumeration method and Langevin dynamics simulation, our simple self-avoiding polymer model reveals robust behaviors (across statics and dynamic studies) despite strong finite-size effects. We observe that as block length increases, polymer compaction intensifies relying on non-specific interaction, leading to longer segregation times. The dynamic study clearly demonstrates the formation of globular lamellar phases and condensed, stable complex structures in long-range block copolymer (BCP) systems, providing a simplified analogy to lamellar-mediated chromatin compaction, which involves structures that are difficult to segregate under physiological conditions. Dominance of specific interaction over non-specific interaction in long range BCP systems leads to phase separation driven self assemblies which provides a simplified analogy to heterochromatin--inactive or stable domains. In contrast, short-range block sequences remain in a coiled state, exhibiting minimal overlap or interaction due to strong short range attraction, which may corresponds to euchromatin regions where diverse epigenetic states coexist, resulting in active, non-condensed structures. We also observe that asymmetric or lateral confinement favors more segregation between the BCPs irrespective of their underlying sequence.

biophysics↗

bioRxiv2024

A preliminary assessment of the genome sequence of the Annual Mercury, Mercurialis annua

SummaryReview of Christenhusz et al., Wellcome Open Research. A high-quality genome sequence of the Annual Mercury, Mercurialis annua is generated as part of the Darwin Tree of Life Project. The Annual Mercury plant is a good study system for evolutionary transitions between sexual systems, mechanisms of sex determination in plants and changes in ploidy level. The XX female sequenced in this study provides a chromosome-level assembly with reasonable contiguity and high gene completeness. We compare the gene completeness of the assembly presented with those of closely related species, including another published assembly of the Annual Mercury generated using a polyploid individual. Annotation and comparative analysis of the organelle genomes suggest complete circular assemblies. However, we note that the NCBI submissions are tagged as linear. The repeat content identified on the autosomes and X chromosome appears comparable, suggesting the sex chromosomes are relatively recent. An alternative possibility is that our preliminary analysis failed to identify repeats unique to the X chromosome or that these repeat regions have not been assembled in the genome. The harder-to-assemble centromere and telomere regions are not annotated in the genome and are potentially incomplete or missing. We identify putative centromere regions with elevated GC content, but they must be validated. The demographic histories reconstructed for the autosomes and X suggest distinct trajectories irrespective of the scaling parameters. Compared to the autosomes, the older histories recorded on the X are a promising avenue for further work to study the origin of the sex chromosome. Our preliminary assessment of the genome sequence suggests the genome is of sufficiently good quality for use as a reference for diverse analysis aimed at answering important eco-evolutionary questions of interest that can be answered using this system.

genomics↗

bioRxiv2021

Immunoinformatic based analytics on T-cell epitope from spike protein of SARS-CoV-2 concerning Indian population.

The whole world is drastically affected by the current pandemic due to severe virus, SARS-CoV-2 and scientists are rigorously looking for the efficient vaccine against it that become an emergent issue. Reverse vaccinology approach may provide us with significant therapeutic leads in this direction and further determination of T-cell / B-cell response to antigen. In the present study, we conducted population coverage analysis referring to the diverse Indian population. By using tools from Immune epitope database (IEDB), HLA- distribution analysis was performed to find the most promiscuous T-cell epitope out of In silico determined epitope of Spike protein from SARS-CoV-2. Selection of these epitopes have been conducted based on their binding affinity with the maximum number of HLA alleles belong to the highest population coverage rate values for the chosen geographical area in India. 404 cleavage sites within the 1288 amino acids sequence of spike glycoprotein were determined by NetChop proteasomal cleavage prediction suggesting that this protein has adequate sites in the protein sequence for cleaving into appropriate epitopes. For population coverage analysis, 221 selected epitopes are considered that shows the projected population coverage as 83.08% with 19.29 average hit (average number of epitope hits/HLA combinations recognized by the population) and 5.91 pc90 (minimum number of epitope hits/HLA combinations recognized by 90% of the population). 54 epitopes are found with the highest coverage among the Indian population and highly conserved within the given spike RBD domain sequence. Docking analysis of each epitope with their respective allele suggests that the epitope NSFTRGVYY represents highest binding affinity with docking score -7.6 kcal/mol with its allele HLA-C*07:01 among all the epitopes. Since the Covid-19 cases are still in progress and seem to remain like this until we find an effective vaccine, moreover in countries like India, vast diversity in the population may present a hindrance to particular vaccine efficiency. Outcomes from this study could be critical to design vaccine against SARS-CoV-2 for a different set of the population within the country.

immunology↗