Biology subjects

Misra, P.

Publications and source records attributed to Misra, P..

9 recordsLinked to original sources

bioRxiv2026

Whole-Genome sequencing of Indigenous Withania somnifera accession and comparative cytochrome P450 phylogenomics

Cytochrome P450 monooxygenases (CYP450s) are key oxidative enzymes that diversify plant specialized metabolites and play a central role in the biosynthesis of bioactive withanolides in Withania somnifera (L.) Dunal. Despite their importance, genome-wide information on CYP450s in W. somnifera has remained elusive. Herein, the first high-quality genome assembly (2.2 Gb, scaffold N50: 47.4 kb) of an Indian W. somnifera cultivar was generated using a hybrid Oxford Nanopore-Illumina sequencing strategy. Comparative analysis with the NCBI reference genome revealed moderate SNP and indel variations, reflecting intraspecific genetic diversity. A comprehensive CYP450 catalog was established and analyzed phylogenomically across nine plant genomes, encompassing both withanolide-producing and non-producing Solanaceae and non-Solanaceae species. Unique CYP families (CYP450A, CYP1194, and CYP705A) were detected exclusively in W. somnifera, suggesting lineage-specific metabolic innovations, while Solanaceae-restricted (CYP82E/M) and absent (CYP81B, CYP6) lineages highlight taxonomic divergence. Across all analyzed genomes, 36 conserved CYP450 subfamilies, including triterpenoid-associated members, were identified, suggesting a shared oxidative framework adaptable to specialized metabolism. Moreover, potential candidate genes in the triterpenoid pathway, including CYP72A692_1, CYP72A560_4, CYP716A48, CYP724B2, and CYP51G1, were identified through phylogenetic integration with functionally validated triterpenoid-modifying enzymes from other plant species. Gene family evolution analysis further revealed contraction of monoterpenoid-related subfamilies (CYP76A), implying a metabolic shift toward triterpenoid specialization. The comprehensive genome assembly and CYPome of W. somnifera offer a valuable resource for functional characterization, evolutionary analysis, and the identification of genes underlying its specialized metabolism. Furthermore, the study advances our understanding of CYP450 diversity and evolution, revealing lineage-specific innovations, conserved subfamilies, and key candidate genes involved in triterpenoid biosynthesis. Together, these findings lay a foundation for future functional studies and pathway engineering aimed at optimizing the metabolic potential of this important medicinal plant.

genomics↗

bioRxiv2026

Improved transcriptome assembly of Monarda citriodora reveals candidate HD-ZIP IV transcription factors involved in trichome development and secondary metabolism

Members of the HD-ZIP transcription factor family play an important role in plant processes, including growth, development, metabolism, and stress response regulation. Among these, the sub-family IV members regulate epidermal cell differentiation, trichome development, and secondary metabolism. Monarda citriodora, an aromatic plant, produces economically important essential oils enriched in thymol. Thymol and other related monoterpenes are primarily biosynthesized and stored in glandular trichomes. Despite its significant economic value, the comprehensive identification of the transcription factor families has not been studied in this plant species. Given the importance of HD-ZIP-IV members in regulating trichome development and secondary metabolism, we identified these members in M. citriodora in the present study. To this end, firstly, we carried out transcriptome sequencing of M. citriodora flowers, and the resulting reads, along with previously sequenced reads, were used to reconstruct a transcriptome assembly. The assembled transcripts represented all major plant parts. Using this improved assembly, HD-ZIP-IV members were identified. Their expression profiles and phylogenetic positions, in conjunction with those of known regulators, identified candidate genes involved in the secondary metabolism and/or trichome development in M. citriodora. Furthermore, through gene co-expression analysis, several McHD-ZIP-IV members were found to be co-expressed with McDXS and McTPS genes. These McHD-ZIP-IV members may serve as key candidate genes for functional analysis to determine the regulation of trichome development in M. citriodora. Taken together, the present study provides a resource for improving M. citriodora using molecular tools.

plant biology↗

bioRxiv2026

Computational Development of a GluN1 Synthetic Peptide Mimetic for Neutralization of Autoantibodies in Anti-NMDAR Autoimmune Encephalitis

Purpose/ObjectiveThis study aimed to design and computationally evaluate a synthetic GluN1-mimetic peptide as a decoy to bind and neutralize pathogenic autoantibodies in anti-NMDA receptor (NMDAR) encephalitis, a severe autoimmune neurological disorder affecting approximately 1.5 per million individuals annually. MethodsKey GluN1 epitope residues (351-390 of the amino-terminal domain) were identified from crystallographic evidence and patient-derived antibody binding studies. Multiple peptide variants were rationally designed to mimic the antibody-binding interface. AlphaFold2 was used to predict peptide structures. Rigid-body docking simulations were conducted with HADDOCK 2.4 to model peptide-antibody complexes, and binding affinities were quantified using PRODIGY. A scrambled peptide control was included to establish docking specificity. ResultsThe top-performing peptide demonstrated favorable predicted binding ({Delta}G = -21.5 kcal/mol, Kd = 1.7 x 10-{superscript 1} M) with an average pLDDT score of 90%, a buried surface area of 3,255.5 [A]{superscript 2}, and 18 intermolecular hydrogen bonds. Relative to the scrambled control ({Delta}G = -8.3 kcal/mol), the designed peptide showed substantially stronger predicted binding. Conclusion/ImplicationsThese results support the validity of an epitope-mimicry design strategy and establish a scalable computational framework for prioritizing peptide decoy candidates applicable to other antibody-mediated autoimmune disorders. Experimental validation remains necessary to confirm real-world efficacy.

bioinformatics↗

bioRxiv2025

Coordinated regulation of trichome morphogenesis and flavonoid pathway by a MYB HDZIP JAZ module in banana (Musa sp.)

O_LITrichomes are epidermal structures that function in defence against biotic and abiotic stresses. The developmental and metabolic aspects of trichomes have not been studied in banana (Musa acuminata). In the present study, we report that banana cultivars with AAA genome contain trichomes on inflorescence stalk. C_LIO_LITranscriptome analysis of epidermal tissues of trichome-rich and trichome-free banana cultivars suggested that genes concerning defence response and specialized metabolism are differentially regulated. Based on the gene expression and phylogenetic analysis, two transcription factors, MaTFR (trichome and flavonol related R2R3-MYB) and MaHDZIV6 (HDZIP-IV), were identified as candidate regulators of trichome development. C_LIO_LIBoth genes partially complemented the glabrous phenotype of trichome-related mutants of Arabidopsis. Transient overexpression and silencing in banana embryogenic cells (ECS) suggested that both MaTFR and MaHDZIV6 regulate the transcription of flavonol biosynthesis genes and modulate flavonoids content. Furthermore, MaTFR was found to directly activate the expression of MaHDZIV6. C_LIO_LITrichome-enriched cultivars have enhanced active JA content compared to trichome-free cultivar suggesting the involvement of JA signalling in regulating trichome development. Two JAZ repressors, MaJAZ5 and MaJAZ8 interacted with MaTFR and attenuated the flavonoid biosynthesis. Our study concludes that the MYB, HDZIP-IV, and JAZ module fine-tunes the flavonoid biosynthesis and the trichome development in banana. C_LI

plant biology↗

bioRxiv2024

Type-B response regulators MaRR_B9 and MaRR_B12 coordinate cytokinin-mediated negative regulation of anthocyanin biosynthesis in banana fruits

O_LIAnthocyanins are pigments responsible for vibrant plant colors and play vital roles in plant physiology. Comparing two banana varieties, grand naine (GN) and red banana (RB), which display significant contrast in anthocyanin pigmentation. C_LIO_LITranscriptomic analysis of GN and RB peel and pulp tissue highlighted cytokinin-specific response regulators, MaRR_B9 and MaRR_B12, as regulators of anthocyanin biosynthesis. C_LIO_LIThrough a combination of physiological, molecular, and biochemical analyses, we demonstrate that MaRR_B9 and MaRR_B12 exert direct regulatory control over key structural genes of anthocyanin biosynthesis, dihydroflavanol reductase (MaDFR) and anthocyanidin synthase (MaANS). MaRR_B9 and MaRRB_12 interact with the promoters of MaDFR and MaANS, repressing the concerned genes in vivo. Overexpression of MaRR_B9 and MaRR_B12 in banana fruits leads to a reduction in anthocyanin content, particularly that of the cyanidin derivative, along with altered expression patterns of MaDFR and MaANS. C_LIO_LIThus, the present study identifies novel regulators of anthocyanin biosynthesis in banana and provides further evidence that the cytokinin regulatory network modifies anthocyanin accumulation in plants. In conclusion, our findings reveal new molecular targets, in the form of MaRRs for the genetic manipulation of anthocyanin content and thereby for the development of stress-resilient and nutritionally enriched crop plants. C_LI

plant biology↗

bioRxiv2024

Invariant Neural Representation of Parts of Speech in the Human Brain

Elucidating the internal representation of language in the brain has major implications for cognitive science, brain disorders, and artificial intelligence. A pillar of linguistic studies is the notion that words have defined functions, often referred to as parts of speech. Here we recorded invasive neurophysiological responses from 1,801 electrodes in 20 patients with pharmacologically-resistant epilepsy while they were presented with two-word phrases consisting of an adjective and a noun. We observed neural signals that distinguished between these two parts of speech. The representation of parts of speech showed invariance across visual and auditory presentation modalities, robustness to word properties like length, order, frequency, and semantics, and even generalized across different languages. The selective signals were circumscribed within a small region in the left lateral orbitofrontal cortex. This selective, invariant, and localized representation of parts of speech extends classic fronto-temporal language models, providing a target for mechanistic and causal tests of how the brain represents basic building blocks of language, and introduces a systematic approach to elucidate the orchestration of more complex aspects of language.

neuroscience↗

bioRxiv2024

Experimental evaluation of a direct fitness effect of the de novo evolved mouse gene Pldi

De novo evolved genes emerge from random non-coding sequences and have, therefore, no homologs from which a function could be inferred. While expression analysis and knockout experiments can provide insights into the function, they do not directly test whether the gene is beneficial for its carrier. Here, we have used a seminatural environment experiment to test the fitness of the previously identified de novo evolved mouse gene Pldi, which is thought to be involved in sperm differentiation. We used a knockout mouse strain for this gene and competed it against its parental wildtype strain for several generations of free reproduction. We found that the knockout (ko) allele frequency decreased consistently across three replicates of the experiment. Using an approximate Bayesian computation framework that simulated the data under a demographic scenario mimicking the experiments demography, we could estimate a fitness coefficient ranging between 0.15 to 0.67 for the wildtype allele compared to the ko allele in males. We conclude that a gene that has evolved de novo from a random intergenic sequence can have a measurable fitness benefit.

evolutionary biology↗

bioRxiv2022

Flavonols contrary affect the interconnected glucosinolate and camalexin biosynthesis pathway in Arabidopsis thaliana

Flavonols are structurally and functionally diverse molecules playing roles in plant biotic and abiotic stress tolerance, auxin transport inhibition, pollen development, etc. Despite their ubiquitous occurrence in land plants and multifunctionality, the effect of perturbation of flavonol biosynthesis over global gene expression and pathways other than flavonoid biosynthesis has not been studied in detail. To understand the signaling role of different flavonol metabolites, herein, we used the flavonol deficient Arabidopsis thaliana loss-of-function mutant flavonol synthase1 (fls1-3) as object of study. Comparative transcriptome and metabolic profiling were used to study the effects of genetic flavonol deficiency and exogenous supplementation with flavonol derivatives (kaempferol, quercetin and rutin) on different cellular processes in the seedling. Various flavonol biosynthesis-related regulatory and structural genes were found to be up-regulated in the fls1-3 mutant which could be reversed by exogenous flavonol feeding. Our manifold comparative studies indicated the modulation of various biological processes and metabolic pathways by flavonols. Camalexin biosynthesis was found to be negatively regulated by flavonols. Interestingly, flavonols appeared to promote the accumulation of aliphatic glucosinolate through transcription factor-mediated up-regulation of biosynthesis genes. Overall, this study provides new insights into molecular mechanisms by which flavonols interfere with the relevant signal chains and their molecular targets and adds new knowledge to the expanding plethora of biological activity of flavonols in plants. SignificanceComparative transcriptome and metabolomic profiling of genetic flavonol deficiency and exogenous flavonol supplementation in A. thaliana seedlings, for the first-time revealed the inverse regulation of interconnected specialized metabolite pathways by flavonol aglycones, and -glycosides. Flavonols negatively regulate camalexin biosynthesis, while promoting the accumulation of aliphatic glucosinolates. Our study adds new insights into the expanding plethora of biological activity of flavonols in plants and will help to uncover the molecular mechanisms by which flavonols interfere with the relevant signal chains and their molecular targets.

plant biology↗

bioRxiv2018

Towards a universal structural and energetic model for prokaryotic promoters

With almost no consensus promoter sequence in prokaryotes, recruitment of RNA polymerase (RNAP) to precise transcriptional start sites (TSSs) has remained an unsolved puzzle. Uncovering the underlying mechanism is critical for understanding the principle of gene regulation. We attempted to search the hidden code in ~16500 promoters, of twelve prokaryotes representing two kingdoms, in their structure and energetics. Twenty eight fundamental parameters of DNA structure including backbone angles, base pair axis, inter base pair and intra base pair parameters were used and information was extracted from X-ray crystallography (XRC) data. Three parameters (solvation energy, hydrogen bond energy and stacking energy) were selected for creating energetics profiles using in-house programs. DNA was found to be inherently designed to undergo a change in every parameter undertaken, from some distance upstream of TSSs to adopt a signature state at these locations in all prokaryotes. These signature states might be the universal hidden codes recognised by RNAP. This observation was reiterated when randomly selected promoter sequences (with little sequence conservation) were subjected to structure generation; all developed into very similar three dimensional structures, quite distinct from those of conventional B-DNA and coding sequences. Fine structural details at important motifs (viz. -11, -35, -75 positions relative to TSS) of promoters reveal novel and pointed insights for RNAP interaction at these locations; it could be correlated that how some particular structural changes at -11 region may allow insertion of RNAP amino acids in inter-base pair space as well as facilitate the flipping out of bases from DNA duplex.

genomics↗