Biology subjects

Gowda, M.

Publications and source records attributed to Gowda, M..

8 recordsLinked to original sources

bioRxiv2026

From Diversity to Discovery: Genome-Wide Insights into the Genetic Landscape of Tropical Maize DH Lines

Understanding the extent and structure of genetic diversity within breeding populations is essential for sustaining long-term genetic gain in maize improvement programs. In this study, a panel of 2,555 maize doubled haploid (DH) lines representing diverse genetic backgrounds was genotyped using 3305 high-quality single nucleotide polymorphism (SNP) markers to assess genome-wide diversity, population structure, and relatedness. The SNPs were distributed across all ten chromosomes, with varying marker densities among genomic regions. Diversity indices revealed moderate polymorphism, with mean gene diversity (0.38) and polymorphic information content (0.30), while the minor allele frequency ranged from 0.04 to 0.50. The low observed heterozygosity (0.04) and high fixation index (0.89) confirmed the expected homozygosity of DH lines. Population structure analysis using sparse non-negative matrix factorization (sNMF) and principal coordinate analysis (PCoA) consistently identified two major genetic clusters corresponding to the established heterotic groups used in CIMMYTs tropical maize breeding pipelines. The Analysis of Molecular Variance (AMOVA) indicated that 36% of genetic variation occurred among populations, 58% among individuals within populations, and 6% within individuals (P = 0.001), confirming significant population differentiation and high within-group diversity. These results demonstrate that the DH panel represents a genetically diverse and well-structured population with limited relatedness among lines. The distinct clustering by heterotic group, coupled with substantial within-group variation, provides a strong foundation for genome-wide association studies, genomic selection, and allele mining for complex adaptive traits. The panels diversity and structure make it an invaluable genomic resource for dissecting trait architecture and accelerating genetic gain in tropical maize breeding programs targeting sub-Saharan Africa and similar environments.

genetics↗

bioRxiv2026

Origin-1: a generative AI platform for de novo antibody design against novel epitopes

0Generative artificial intelligence has advanced antibody discovery, yet de novo design of therapeutic antibodies against targets with "zero-prior" epitopes remains a fundamental challenge. We define "zero-prior" epitopes as target sites lacking structural data from any reported antibody-antigen or protein-protein complex involving the target. Here we present Origin-1, a generative AI platform that overcomes this by integrating epitope-conditioned all-atom structure generation, paired complementarity determining region sequence design, and a specialized co-folding-based scoring protocol to select antibody designs predicted to be high-confidence, specific binders with favorable developability. We evaluated Origin-1 on a panel of ten targets selected to have no available protein-protein complex structures and minimal homology ([≤]60% sequence identity) to proteins with known complexes, creating stringent design conditions. In fewer than one hundred design attempts per target, we identified developable, specific antibodies, validated across multiple biophysical and developability assays, for four targets: COL6A3, AZGP1, CHI3L2, and IL36RA, with functional inhibition demonstrated for IL36RA. Cryogenic electron microscopy confirmed the atomic accuracy of our designs, revealing complexes that closely matched the computational models with high structural fidelity (3.0-3.3 [A] resolution; 0.83-0.91 DockQ). Furthermore, we employed AI-guided affinity maturation to optimize a de novo antibody binder against IL36RA, producing functional antagonists with sub-nanomolar affinities and a top EC50 of 12.3 nM. These results demonstrate a framework for targeting epitopes without structural precedent, expanding the programmable therapeutic antibody landscape.

molecular biology↗

bioRxiv2025

Genetic Insights from Line x Tester Analysis of Maize Lethal Necrosis Testcrosses for Developing Multi-Stress-Resilient Hybrids in Sub-Saharan Africa

A systematic evaluation of maize hybrid performance and combining ability was conducted to enhance resistance to maize lethal necrosis (MLN), drought tolerance, and grain yield (GY) in eastern and southern Africa. Thirty-eight MLN-tolerant, lines were crossed with 29 single-cross testers to generate 437 testcross hybrids, evaluated under managed MLN inoculation, drought stress, and optimum conditions across multiple locations. Continuous variation in GY, disease severity, and agronomic traits confirmed quantitative inheritance, with strong positive correlations between GY and ears per plant and negative correlations between MLN severity and yield. Variance analyses revealed highly significant genotypic and genotype x environment interactions, with additive effects predominating across environments (Bakers ratios 0.85-0.99; heritability 0.69-0.88), supporting effective selection based on general combining ability (GCA). Superior MLN-tolerant hybrids, such as (CKLMARSI0037/CKLTI0139)//CKDHL120312, achieved up to 5.75 t ha-{superscript 1} under MLN, exceeding commercial checks by over fivefold. Under optimum and drought conditions, top hybrids maintained high yield, foliar disease resistance, short anthesis-silking intervals, and delayed senescence. Specific combining ability (SCA) effects highlighted stress-specific non-additive interactions, particularly under drought, underscoring the need for targeted parental selection. GCA analyses identified across environment and environment-specific favorable parents, including CKDHL120312, CKDHL140910, CKLMARSI0037/CKLTI0139, and CML322/CML543, while GGE biplots confirmed tester discrimination and representativeness. These findings demonstrate that integrating MLN resistance, drought tolerance, and high yield is achievable without compromising other agronomic performance. The study provides a robust framework for selecting elite parents and testers, exploiting additive and non-additive genetic effects, and developing resilient, high-performing maize hybrids for sub-Saharan Africa.

plant biology↗

bioRxiv2025

Genome Sequencing, Molecular Marker Development and Genetic Diversity Assessment of Economically Important Vulnerable Tree Species Saraca asoca (Roxb.) W.J de Wilde

Saraca asoca, is an understory tree along streams in evergreen to semi-evergreen forests up to 600 m. It is an important tree in cultural tradition and medicinally significant. It is native to India and Sri Lanka. Globally the species is found to occur in India, Sri Lanka, Myanmar, Bangladesh. It was introduced in Malaysia. Within India, its found in Western Ghat and Eastern Ghat. It is occasionally planted in gardens. Saraca asoca is known for its extensive pharmacological properties, particularly its bark is used in treating menorrhagia, dysfunctional uterine bleeding, hemorrhagic dysentery, and other gynecological issues, it holds a prominent place in Ayurvedic medicine. This study was undertaken to sequence the whole genome of Saraca asoca using the Illumina HiSeq2500 platform, and evaluating the genetic diversity among samples from Kolluru and other locations in southern India through Genotyping by Sequencing (GBS). Analysis of 49 samples established genetic diversity relationships using a distance matrix. Sequencing yielded 1.6 Gb, covering 76% of the estimated genome size. The genome includes 764 million bases of repetitive DNA elements. A survey of Simple Sequence Repeats (SSRs) identified 584,615 SSRs, with 236,123 sequences containing SSRs. Utilizing the KEGG database, biosynthesis pathways for catechin and epicatechin within the flavonoid synthesis pathway were identified. This comprehensive genomic analysis of Saraca asoca (Sita Ashoka) provides critical insights for conservation efforts aimed at preserving this vulnerable species, Saraca asoca (Roxb.) Willd.

genomics↗

bioRxiv2024

A POLR3B-variant reveals a Pol III transcriptome response dependent on La protein/SSB

RNA polymerase III (Pol III, POLR3) synthesizes tRNAs and other small non-coding RNAs. Human POLR3 pathogenic variants cause a range of developmental disorders, recapitulated in part by mouse models, yet some aspects of POLR3 deficiency have not been explored. We characterized a human POLR3B:c.1625A>G;p.(Asn542Ser) disease variant that was found to cause mis-splicing of POLR3B. Genome-edited POLR3B1625A>G HEK293 cells acquired the mis-splicing with decreases in multiple POLR3 subunits and TFIIIB, although display auto-upregulation of the Pol III termination-reinitiation subunit POLR3E. La protein was increased relative to its abundant pre-tRNA ligands which bind via their U(n)U-3-termini. Assays for cellular transcription revealed greater deficiencies for tRNA genes bearing terminators comprised of 4Ts than of [≥]5Ts. La-knockdown decreased Pol III ncRNA expression unlinked to RNA stability. Consistent with these effects, small-RNAseq showed that POLR3B1625A>Gand patient fibroblasts express more tRNA fragments (tRFs) derived from pre-tRNA 3-trailers (tRF-1) than from mature-tRFs, and higher levels of multiple miRNAs, relative to control cells. The data indicate that decreased levels of Pol III transcripts can lead to functional excess of La protein which reshapes small ncRNA profiles revealing new depth in the Pol III system. Finally, patient cell RNA analysis uncovered a strategy for tRF-1/tRF-3 as POLR3-deficiency biomarkers.

molecular biology↗

bioRxiv2022

Genome Sequencing Unravelled C3, C4 and CAM Photosynthetic Pathways in Ficus religiosa

BackgroundPeepal/Bodhi tree (Ficus religiosa L.) is an important, long-lived keystone ecological species. Communities on the Indian subcontinent have extensively employed the plant in Ayurveda, traditional medicine, and spiritual practices. The Peepal tree is often thought to produce oxygen both during the day and at night by Indian folks. The goal of our research was to produce molecular resources using whole-genome and transcriptome sequencing techniques. ResultsThe complete genome of the Peepal tree was sequenced using two next-generation sequencers Illumina HiSeq1000 and MGISEQ-2000. We assembled the draft genome of 406 Mb, using a hybrid assembly workflow. The genome annotation resulted in 35,093 protein-coding genes; 53% of its genome consists of repetitive sequences. To understand the physiological pathways in leaf tissues, we analyzed photosynthetically distinct conditions: bright sunny days and nights. The RNA-seq analysis supported the expression of 26,479 unigenes. The leaf transcriptomic analysis of the diurnal and nocturnal periods revealed the expression of the significant number of genes involved in the carbon-fixation pathway. ConclusionsThis study presents a draft hybrid genome assembly for F. religiosa and its functional annotated genes. The genomic and transcriptomic data-derived pathways have been analyzed for future studies on the Peepal tree.

genomics↗

bioRxiv2019

Next-Gen sequencing of novel pandemic swine flu virus in India revealed novel mutations across the genome

The Influenza A H1N1 virus of 2009 was the first pandemic flu virus of the 21st century. Identifying the emergence of mutations in rapidly mutating Influenza viruses that allow increased transmission or confer resistance are invaluable to global outbreak response. Here we recovered 5 complete Influenza A genomes from 4 oropharygeal swabs and one cell culture isolate from a severe Indian outbreak of flu in early 2015. Multiple amino acids substitutions including those known to confer resistance to Oseltamivir and increased pathogenecity in mice were found in the Neuraminidase gene. Additional mutations both reported and novel were found throughout the genome compared to the vaccine strain (California/04/2009). All eight segments of the complete genomes were found to be genetically related to the 2009 pandemic strain, A(H1N1)pdm09 and belonging to the emerging genogroup 6B. This group was found to be of south East Asian origin by time scale phylogentic analysis. A phylogeographic analysis revealed 39 significant migration events among globally circulating viruses. This study is the first extensive complete genome and phylogeographic analysis of 2015 Indian A(H1N1) pdm09 viruses. We report several novel mutations in the 2015 Indian strains which need to be evaluated for effect on viral replication, transmission and resistance to therapy. The identification of mutant A(H1N1)pdm09 from India warrants continuous monitoring of viral evolution for implementation of suitable medical countermeasures.

genomics↗

bioRxiv2017

Complete assembly of a dengue virus type 3 genome from a recent genotype III clade by metagenomic sequencing of serum

BackgroundMosquito-borne flaviviruses causing diseases such as dengue and Japanese encephalitis are devastating, particularly in the tropics. Although, multiple flaviviruses are known to co-circulate in India, when a patient presents with febrile illness, testing is usually limited to specific pathogens. Unbiased metagenomic sequencing of febrile cases can reveal the presence of multiple pathogens and provide complete genome information. Sequence information, a cornerstone for tracing virus evolution, is relevant for the design of vaccines and therapeutics. In order to assess the usefulness of unbiased metagenomic sequencing for the identification of viruses associated with febrile illness, we sequenced serum from four individuals and plasma from one individual, all hospitalized at a tertiary care centre in South India with severe or prolonged febrile illnesses, together with one healthy control in 2014.\n\nResultsWe identified and assembled a complete dengue virus type 3 (DENV3) sequence from the serum of a case classified as severe dengue. We also found a small number of Japanese encephalitis virus (JEV) sequences in the serum of two adults with febrile illness, including the one who had dengue. Phylogenetic analysis of the dengue sequence indicates that it belongs to a predominantly Asian, DENV3, genotype III clade. It had an estimated divergence time of 13.86 years (95% Highest Posterior Densities 12.94 - 14.83 years) with the closest Indian strain. Amino acid substitutions were present throughout the sequenced genome, including 11 substitutions in the antigenic envelope protein compared to the strain used for the development of the first commercial dengue vaccine. Of these one substitution (E361D) was unique and six were in critical antigenic sites.\n\nConclusionsWe demonstrate that both genome assembly and detection of a low number of viral sequences are possible by unbiased sequencing of clinical material. Complete dengue virus sequence analysis places the sequenced genome in a recent, predominantly Asian clade within genotype III of DENV3. The detection of JEV, an agent not routinely tested in febrile illness in India, warrants further analysis and highlights the need to study co-circulating flaviviruses in parallel.

microbiology↗