Biology subjects

Kumar, P.

Publications and source records attributed to Kumar, P..

At least 253 records · Page 14Linked to original sources

bioRxiv2019

Rapid and independent evolution of ancestral and novel defenses in a genus of toxic plants (Erysimum, Brassicaceae)

Phytochemical diversity is thought to result from coevolutionary cycles as specialization in herbivores imposes diversifying selection on plant chemical defenses. Plants in the speciose genus Erysimum (Brassicaceae) produce both ancestral glucosinolates and evolutionarily novel cardenolides as defenses. Here we test macroevolutionary hypotheses on co-expression, co-regulation, and diversification of these potentially redundant defenses across this genus. We sequenced and assembled the genome of E. cheiranthoides and foliar transcriptomes of 47 additional Erysimum species to construct a highly resolved phylogeny, revealing that cardenolide diversity increased rapidly rather than gradually over evolutionary time. Concentrations, inducibility, and diversity of the two defenses varied independently among species, with no evidence for trade-offs. Closely related species shared similar cardenolide traits, but not glucosinolate traits, likely as a result of specific selective pressures acting on distinct molecular diversification mechanisms. Ancestral and novel chemical defenses in Erysimum thus appear to provide complementary rather than redundant functions.

plant biology↗

bioRxiv2019

Adverse childhood experiences in families with multiple members diagnosed to have psychiatric illnesses

ObjectiveAdverse Childhood Experiences (ACEs) are linked to the development of a number of psychiatric illnesses in adulthood. Our study examined the pattern of ACEs and their relation to the age of onset (AAO) of major psychiatric conditions in individuals from families that had [≥] 2 first degree relatives with major psychiatric conditions (multiplex families) identified as part of an ongoing longitudinal study.\n\nMethodsOur sample consisted of 509 individuals from 215 families. Of these, 268 were affected i.e diagnosed with bipolar disorder (BPAD) (n=61), obsessive-compulsive disorder (OCD) (n=58), schizophrenia (n=52), substance dependence (SUD) (n=59), or co-occurring diagnoses (n=38); while 241 were at-risk first degree relatives (FDRs) who were either unaffected (n=210) or had other depressive or anxiety disorders (n=31). All individuals were evaluated using the Adverse Childhood Experiences - International Questionnaire (ACE-IQ) and ACE binary and frequency scores were calculated.\n\nResultsIt was seen that affected males, as a group, had the greatest ACE scores in our sample. A cox mixed-effects model fit by gender revealed that higher ACE binary and frequency scores were associated with significantly increased risk for an earlier AAO of psychiatric diagnoses in males. A similar model that evaluated the effect of diagnosis revealed an earlier AAO in OCD and SUD, but not in schizophrenia and BPAD.\n\nConclusionsOur study indicates that ACEs brought forward the onset of major psychiatric conditions in men and in individuals diagnosed with OCD and SUD. Ongoing longitudinal assessments in FDRs from these families are expected to identify mechanisms underlying this relationship.

neuroscience↗

bioRxiv2019

Longitudinal bioluminescent imaging of HIV-1 infection during antiretroviral therapy and treatment interruption in humanized mice

Non-invasive bioluminescent imaging (NIBLI) of HIV-1 infection dynamics allows for real-time monitoring of viral spread and the localization of infected cell populations in living animals. In this report, we describe full-length replication-competent GFP and Nanoluciferase (Nluc) expressing HIV-1 reporter viruses from two clinical transmitted / founder (T/F) stains: TRJO.c and Q23.BG505. By infecting humanized mice with these HIV-1 T/F reporter viruses, we were able to directly monitor longitudinal viral spread at whole-animal resolution via NIBLI at a sensitivity of as few as 30-50 infected cells. Bioluminescent signal strongly correlated with HIV-1 infection and responded proportionally to virus suppression in vivo in animals treated daily with a combination antiretroviral therapy (cART) regimen. Longitudinal NIBLI following cART withdrawal visualized tissue-sites that harbored virus during infection recrudescence. Notably, we observed rebounding infection in the same lymphoid tissues where infection was first observed prior to ART treatment. Our work demonstrates the utility of our system for studying in vivo viral infection dynamics and identifying infected tissue regions for subsequent analyses.\n\nAuthor SummaryNon-invasive bioluminescent imaging (NIBLI) in small animals allows for in vivo longitudinal imaging of infection spread and pathogenesis. We have taken advantage of the small luciferase reporter protein, Nanoluciferase (Nluc), to generate a replication-competent HIV-1 reporter virus to allow for NIBLI of viral infection in humanize mice. NIBLI via Nluc enabled us to directly visualize longitudinal spreading patterns before, during, and after interruption of daily doses of combined antiretroviral therapy (cART). We observed that rebounding infection often emerged in tissue regions originally associated with infected cells prior to cART treatment. Thus, Nluc-based NIBLI of HIV-1 infection can be used as an experimental tool to study early events involved in viral dissemination and spread from initial sites of infection to draining lymphoid tissues as well as locate infected tissues for subsequent cellular characterization of HIV-1 infected cells.

microbiology↗

bioRxiv2019

Pan-active imidazolopiperazine antimalarials target the Plasmodium falciparum intracellular secretory pathway

AO_SCPLOWBSTRACTC_SCPLOWOne of the most promising new compound classes in clinical development for the treatment of malaria is the imidazolopiperazines (IZPs) class. Human trials have demonstrated that members of the IZP series, which includes KAF156 (Ganaplacide) and GNF179, are potent and effective against Plasmodium symptomatic asexual blood-stage infections. Unlike other commonly used antimalarials, they also prevent transmission and block future infection in animal models. Despite the identification of several Plasmodium falciparum resistance mechanisms including mutations in ER-localized PfCARL (PfEMP65), Acetyl-coA transporter, and PfUGT transporter, IZPs mechanism of action remains unknown.\n\nTo investigate, we combined in vitro evolution and whole-genome analysis in the model organism Saccharomyces cerevisiae with molecular, metabolomic, and chemogenomic methods, in P. falciparum. S. cerevisiae clones that resist IZP activity carry multiple mutations in genes that encode endoplasmic reticulum(ER)-based lipid homeostasis and autophagy including elo2, elo3, sur2, atg15 and lcb4, as well as ER-based sec66. In Plasmodium, IZPs cause inhibition of protein trafficking, block the establishment of new permeation pathways and result in ER expansion. We also observe sensitization with other secretion inhibitors such as brefeldin A and golgicidin as well as synthetic lethality with PfSEC62. Our data show that IZPs target the secretory pathway and highlight a novel mechanism for blocking parasite growth and development that is distinct from those of standard compounds used to treat malaria. In addition, we provide physiological signatures and hallmarks for inhibitors that work through this mechanism of action and show that IZPs are tool compounds for studying ER-dependent protein processing in different species.

microbiology↗

bioRxiv2019

Defining the microenvironment landscape of bladder cancer using highly multiplexed spatial genomic and proteomic analysis

Muscle-invasive bladder cancer (MIBC) is an aggressive disease with limited therapeutic options. PD-1 pathway targeting immunotherapies have been approved to treat advanced bladder cancer, but most patients exhibit primary resistance, suggesting that immune evasion mechanisms exist. The PPAR{gamma} pathway has been identified as a potential therapeutic target in MIBC that is associated with reduced CD8+ T-cell infiltration and increased resistance to immunotherapies. We comprehensively profiled the tumor microenvironment (TME) in formalin-fixed, paraffin-embedded (FFPE) tissues from a cohort of PPAR{gamma}high (n=13) and PPRAR{gamma}low (n=12) MIBC, integrating bulk gene expression, targeted mutation sequencing, immunohistochemistry and multiplex spatial profiling of RNA and protein expression on the GeoMx Digital Spatial Profiling (DSP) platform. Molecular subtyping was consistent between traditional methods and GeoMx profiling, and, in this cohort, we observed little evidence of spatial heterogeneity in tumor subtyping. The previously characterized T-cell exclusion phenotype of PPAR{gamma}high MIBC was recapitulated on the GeoMx platform and was further extended to show that this is a general phenomenon across immune cell types, supporting potential combination of PPAR{gamma} inhibition with ICIs. Furthermore, we found that while immune cells were excluded from PPAR{gamma}high tumors, the stromal compartment from these tumors was not significantly different than those PPAR{gamma}low tumors. By preserving spatial relationships during the GeoMx analysis, we also identify a novel association between lower immune cell expression in the tumors and higher expression of {beta}-catenin in the stroma, and differential expression of other WNT pathway members associated with PPAR{gamma} activity.\n\nOne Sentence SummaryA new method for capturing tumor-immune signaling in FFPE tissues explores how the PPARG signaling axis is associated with immune cell exclusion in bladder cancer.

cancer biology↗

bioRxiv2019

Transcriptomic Analysis of the Neurogenesis Signature suggests Continued but Minimal Neurogenesis in the Adult Human Hippocampus

PurposeSince immunohistological investigations have given rise to divergent perspectives about continued hippocampal neurogenesis in adult humans, a comprehensive transcriptomic analysis of the neurogenesis signature markers supplemented with insights from gliogenesis and apoptotic markers (in context to the developmental stages across age) may discern important aspects and may well be the appropriate methodology for resolving this conflict.\n\nMaterials and MethodsRNA expression data for the salient neurogenesis, gliogenesis, and apoptotic marker genes in post-mortem human hippocampal tissue of the Prenatal (n=15), Infant/Early childhood (n= 5), Adolescence (n=4), and Adulthood (n=6) ages were downloaded from Allen Brain Atlas database (http://www.brainspan.org/rnaseq). Gene expression data was categorized, median values were computed, and age group specific differential expression was statistically analyzed (the confidence level of 95%, p value [≤] 0.05 is used).\n\nResultsA sharp fall in prenatal to infant/early childhood expression was observed for all studied neurogenesis markers, except that for the post-mitotic late maturation (CALB1, CALB2, MAP2, NEUN, STMN2) which showed no significant differences in expression profiles. A continued post childhood decrease across advancing age was observed in the neural stem cells and progenitor markers with insignificant differences across close age groups. Uniquely, the postnatal sharp fall of KI67 and TBR2 continued across advancing age groups, reached near baseline until adolescent age. The immature granule cell, post mitotic early maturation, and late maturation markers showed a maintained or slightly increased (albeit insignificant) post childhood expression. The gliogenesis markers mostly showed a significant downregulation between prenatal and infant /early childhood age groups; this decline was persistent thereafter with insignificant differences between close age groups. A continued postnatal decrease occurred in apoptotic markers with observable, but insignificant, differences between adolescent and adult age.\n\nConclusionsOur findings indicate a possibility of continued but minimal neurogenesis in the adult human hippocampus. A significant part of the newborn cells in the neurogenic niche may be glial cells.\n\n(Findings of this study were first presented at the Annual Meeting of Society for Neuroscience (SFN), 3rd-7th November, 2018, San Diego, USA. https://abstractsonline.com/pp8/#!/4649/presentation/37213)\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=153 SRC=\"FIGDIR/small/664995v1_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (43K):\norg.highwire.dtl.DTLVardef@3268f3org.highwire.dtl.DTLVardef@18855bborg.highwire.dtl.DTLVardef@1b46bdaorg.highwire.dtl.DTLVardef@14b929_HPS_FORMAT_FIGEXP M_FIG Graphical Abstract\n\nC_FIG HighlightsO_LIA varying but continued fall in expression was observed for all studied neurogenesis markers across advancing age groups, except that for the immature granule cells, early and post-mitotic late neuronal maturation markers.\nC_LIO_LIA continued postnatal sharp fall of progenitor markers KI67 and TBR2 reached near baseline until adolescent age.\nC_LIO_LIGliogenesis markers showed continued but insignificant fall in expression post infant/early childhood.\nC_LIO_LIApoptotic markers showed continued post infant/early childhood downfall but changes were negligible between adolescent and adult age.\nC_LI

neuroscience↗

bioRxiv2019

Exogenous application of KNO3 elevates the salinity tolerance of Stevia rebaudiana through ion homeostasis mechanism

Though relatively little is understood of adaptation, physiological and metabolic changes of Stevia rebaudiana under exposure to salinity stress, it is hypothesized that exogenous application of potassium (K+) could elevates the salinity tolerance through ions homeostasis. Thus, an experiment was conducted with twenty treatment combinations comprising four salinity levels (irrigation with normal water as control and three level of NaCl at 40, 80 and 120 mM) and five different concentrations of KNO3 (0.0, 2.5, 5.0, 7.5, and 10.0 g L-1). Dry leaf yield was not negatively affected with mild salinity (40 mM). However, the detrimental effects were observed at moderate and higher salinity levels (80 and 120 mM). The uptakes of K+, Ca2+, and N were significantly reduced at higher salinity level, whereas accumulations of Na+ and Cl- ions in plant tissues were substantially increased. Proline content in leaf was also increased significantly (P[≤]0.05) in response to salt stress. Among the foliar application, KNO3 at 5.0 gL-1 registered significantly (P[≤]0.05) higher dry leaf yield compared with control. Exogenous application of K+ under moderate salinity stress maintained ion balance in cytosol, particularly K: Na. Thus, the salinity tolerance of stevia can be elevated to some extent through exogenous application of K+.\n\nHighlightThe detrimental effects of moderate and higher salinity levels on growth and dry leaf yield of stevia were observed. However, tolerance level can be elevated through exogenous application of KNO3.

plant biology↗

bioRxiv2019

Histone acetylome-wide association study of tuberculosis

Host-cell chromatin changes are thought to play an important role in the pathogenesis of infectious diseases. Here, we describe the first histone acetylome-wide association study (HAWAS) of an infectious disease, based on genome-wide H3K27 acetylation profiling of peripheral granulocytes and monocytes from subjects with active Mycobacterium tuberculosis (Mtb) infection and healthy controls. We detected >2,000 differentially acetylated loci in either cell type in a Chinese discovery cohort, which were validated in a subsequent multi-ethnic cohort, thus demonstrating that HAWAS can be independently corroborated. Acetylation changes were correlated with differential gene expression in a third cohort. Differential acetylation was enriched near potassium channel genes, including KCNJ15, which modulated Akt-mTOR signaling and promoted Mtb clearance in vitro. We performed histone acetylation QTL analysis on the dataset and identified candidate causal variants for immune phenotypes. Our study serves as proof-of-principle for HAWAS to infer mechanisms of host response to pathogens.

immunology↗

bioRxiv2019

Systemic sclerosis is a disease of a prematurely senescent, inflammatory and activated immunome

Systemic sclerosis (SSc) is an autoimmune disease characterised by excessive fibrosis of skin and internal organs, and vascular dysfunction. Association of T and B cell subsets have been reported in SSc, however there is lack of systematic studies of functional relations between immune cell subsets in this disease. This lack of mechanistic knowledge hampers targeted intervention. In the current study we sought to determine differential immune cell composition and their interactions in peripheral blood of SSc patients. Mononuclear cells from blood of SSc patients and healthy controls (HC) were analysed by mass cytometry using a 36 marker (cell-surface and intracellular) panel. Transcriptome analysis (m-RNA sequencing) was performed on sorted T and B cell subsets. Unsupervised clustering analysis revealed significant differences in the frequencies of T and B cell subsets in patients. Correlation network analysis highlighted an overall dysregulated immune architecture coupled with domination of inflammatory senescent T cell modules in SSc patients. Transcriptome analysis of sorted immune cells revealed an activated phenotype of CD4 and MAIT cells in patients, accompanied with increased expression of inhibitory molecules, reminiscent of phenotype exhibited by functionally adapted, exhausted T cells in response to chronic stimulation. Overall this study provides an in-depth analysis of the systemic immunome in SSc, highlighting the potential pathogenic role of inflammation and chronic stimulation mediated \"premature senescence\" of immune cells.\n\nONE SENTENCE SUMMARYThe immune architecture in Systemic sclerosis is altered and reminiscent of chronic stimulatory environment led premature senescence of immune cells.

immunology↗

bioRxiv2019

Establishing reference samples for detection of somatic mutations and germline variants with NGS technologies

We characterized two reference samples for NGS technologies: a human triple-negative breast cancer cell line and a matched normal cell line. Leveraging several whole-genome sequencing (WGS) platforms, multiple sequencing replicates, and orthogonal mutation detection bioinformatics pipelines, we minimized the potential biases from sequencing technologies, assays, and informatics. Thus, our \"truth sets\" were defined using evidence from 21 repeats of WGS runs with coverages ranging from 50X to 100X (a total of 140 billion reads). These \"truth sets\" present many relevant variants/mutations including 193 COSMIC mutations and 9,016 germline variants from the ClinVar database, nonsense mutations in BRCA1/2 and missense mutations in TP53 and FGFR1. Independent validation in three orthogonal experiments demonstrated a successful stress test of the truth set. We expect these reference materials and \"truth sets\" to facilitate assay development, qualification, validation, and proficiency testing. In addition, our methods can be extended to establish new fully characterized reference samples for the community.

bioinformatics↗

bioRxiv2019

The hypoxic ventilatory response is facilitated by the activation of Lkb1-AMPK signalling pathways downstream of the carotid bodies

We recently demonstrated that the role of the AMP-activated protein kinase (AMPK), a ubiquitously expressed enzyme that governs cell-autonomous metabolic homeostasis, has been extended to system-level control of breathing and thus oxygen and energy (ATP) supply to the body. Here we assess the contribution to the hypoxic ventilatory response (HVR) of two upstream kinases that govern the activities of AMPK. Lkb1, which activates AMPK in response to metabolic stress and CaMKK2 which mediates the alternative Ca2+-dependent mechanism of AMPK activation. HVRs remained unaffected in mice with global deletion of the CaMKK2 gene. By contrast, HVRs were markedly attenuated in mice with conditional deletion of LKB1 in catecholaminergic cells, including carotid body type I cells and brainstem respiratory networks. In these mice hypoxia evoked hypoventilation, apnoea and Cheyne-Stokes-like breathing, rather than hyperventilation. Attenuation of HVRs, albeit less severe, was also conferred in mice carrying [~]90% knockdown of Lkb1 expression. Carotid body afferent input responses were retained following either [~]90% knockdown of Lkb1 or AMPK deletion. In marked contrast, LKB1 deletion virtually abolished carotid body afferent discharge during normoxia, hypoxia and hypercapnia. We conclude that Lkb1 and AMPK, but not CaMKK2, facilitate HVRs at a site downstream of the carotid bodies.

physiology↗

bioRxiv2019

Coupling multiplex pre-amplification and droplet digital PCR for longitudinal monitoring of ESR1 and PIK3CA mutations from plasma cell-free DNA

Here we report on the development of a sensitive and cost-effective method to longitudinally track ESR1 and PIK3CA mutations from cfDNA in patients with metastatic breast cancer (MBC) using a streamlined and de-centralized workflow. Hotspot mutations in ESR1 have been shown to cause resistance to aromatase inhibitor-based and anti-estrogenic therapies, while PIK3CA mutations have high prevalence in MBC. As a result, their utility as circulating biomarkers to predict or monitor response in the clinical development of investigational compounds has been the focus of many studies. Six regions in ESR1 and PIK3CA genes containing 20 hotspot mutations were pre-amplified, followed by optimized singleplex ddPCR assays to detect allele frequencies of individual mutations. Without pre-amplification, the limit of detection (LOD) and limit of linearity (LOL) of individual ddPCR assays were at 0.05-0.1% and 0.25% level, respectively. With pre-amplification, the LOD and LOL were slightly elevated at 0.1-0.25% and 0.25-0.5% levels, respectively. High concordance was achieved to the BEAMing assay (Sysmex Inostics) for mutation positive assays (r=0.98, P<0.0001). In conclusion, coupling pre-amplification and ddPCR assays allowed us for the detection of up to 20 hot spot mutations in ESR1 and PIK3CA with high sensitivity and reproducibility.

genetics↗

bioRxiv2019

HiVA: an integrative wet- and dry-lab platform for haplotype and copy number analysis of single-cell genomes

Haplotyping is imperative for comprehensive analysis of genomes, imputation of genetic variants and interpretation of error-prone single-cell genomic data. Here we present a novel sequencing-based approach for whole-genome SNP typing of single cells, and determine genome-wide haplotypes, the copy number of those haplotypes as well as the parental and segregational origin of chromosomal aberrations from sequencing- and array-based SNP landscapes of single cells. The analytical workflow is made available as an interactive web application HiVA (https://hiva.esat.kuleuven.be).

genomics↗

bioRxiv2019

Extrachromosomal circular DNA, microDNA, without canonical promoters produce short regulatory RNAs that suppress gene expression

Interest in extrachromosomal circular DNA (eccDNA) molecules has increased recently because of their widespread presence in normal cells across every species ranging from yeast to humans, their increased levels in cancer cells, and their overlap with oncogenic and drug-resistant genes. However, the majority of eccDNA (microDNA) are too small to carry protein coding genes. We have tested functional capabilities of microDNA, by creating artificial microDNA molecules mimicking known microDNA sequences and have discovered that they express functional small regulatory RNA including microRNA and novel si-like RNA. MicroDNA is transcribed in vitro and in vivo independent of a canonical promoter sequence. MicroDNA which carry miRNA genes form transcripts which are processed into mature miRNA molecules, through the endogenous RNA-interference pathway, which repress a luciferase reporter gene as well as endogenous mRNA targets of the miRNA. Further, microDNA containing sequences of exons repress the endogenous gene from which the microDNA was derived through the formation of novel si-like RNA. We also show that endogenous microDNA associate with RNA polymerases subunits POLR2H and POLR3F. Together, these results suggest that microDNA may modulate gene expression through the production of both known and novel regulatory small RNA.

molecular biology↗

bioRxiv2019

Distributed DNA-based Communication in Populations of Synthetic Protocells

Developing distributed communication platforms based on orthogonal molecular communication channels is a crucial step towards engineering artificial multicellular systems. Here, we present a general and scalable platform entitled Biomolecular Implementation of Protocellular Communication (BIO-PC) to engineer distributed multichannel molecular communication between populations of non-lipid semipermeable microcapsules. Our method leverages the modularity and scalability of enzyme-free DNA strand-displacement circuits to develop protocellular consortia that can sense, process and respond to DNA-based messages. We engineer a rich variety of biochemical communication devices capable of cascaded amplification, bidirectional communication and distributed computational operations. Encapsulating DNA strand-displacement circuits further allows their use in concentrated serum where non-compartmentalized DNA circuits cannot operate. BIO-PC enables reliable execution of distributed DNA-based molecular programs in biologically relevant environments and opens new directions in DNA computing and minimal cell technology.

synthetic biology↗

bioRxiv2018

E74 like ETS transcription factor 3 (ELF3) is a negative regulator of epithelial-mesenchymal transition in bladder carcinoma

Transcription factors are known to be commonly deregulated in various cancers. The E74 like ETS transcription factor 3 (ELF3) expression is restricted to epithelial tissue. In the present study, we evaluated the role of ELF3 in the pathogenesis of bladder carcinoma (BCa) using cell line model. The cell lines with low expression of ELF3 showed increased expression of mesenchymal markers and decreased expression of epithelial markers. Immunofluorescence and immunohistochemical analysis of ELF3 showed selective expression in low-grade BCa cell lines and tumor tissues, respectively. We demonstrated that overexpression of ELF3 in UMUC3, a mesenchymal BCa cell line resulted in reduced invasion and decreased expression of mesenchymal markers. Furthermore, using publicly available data, we found that low expression of ELF3 was associated with increased risk and poor overall survival rate in BCa. In conclusion, ELF3-modulated reversal of EMT might be a useful strategy in the treatment of bladder cancer.

cancer biology↗

bioRxiv2018

CompStor Novos: a low cost yet fast assembly-based variant calling for personal genomes

Application of assembly methods for personal genome analysis from next generation sequencing data has been limited by the requirement for an expensive supercomputer hardware or long computation times when using ordinary resources. We describe CompStor Novos, achieving supercomputer-class performance in de novo assembly computation time on standard server hardware, based on a tiered-memory implementation. Run on commercial off-the-shelf servers, Novos assembly is more precise and 10-20 times faster than that of existing assembly algorithms. Furthermore, we integrated Novos into a variant calling pipeline and demonstrate that both compute times and precision of calling point variants and indels compare well with standard alignment-based pipelines. Additionally, assembly eliminates bias in the estimation of allele frequency for indels and naturally enables discovery of breakpoints for structural variants with base pair resolution. Thus, Novos bridges the gap between alignment-based and assembly-based genome analyses. Extension and adaption of its underlying algorithm will help quickly and fully harvest information in sequencing reads for personal genome reconstruction.

genomics↗

bioRxiv2018

Comparison between QST and ΦST indices in an endangered Boswellia serrata Roxb: Implications for conservation

Boswellia serrata, an economically important indigenous tree of dry deciduous forests, provides oleoresin gum of pharmaceutical significance and excellent pulp for paper industries, but faces threat to extinction due to poor natural regeneration and commercial exploitation. 240 individuals of the species representing 12 locations of its natural distribution in central India were investigated to compare the genetic differentiation indices, QST for GBH and wood fiber length and {phi}ST for neutral (RAPD+ISSR) markers. The comparison for paired locations was more informative than for metapopulation. The most paired locations were either under the stabilizing selection (QST (L) < {Phi}ST (L)) or in the genetic drift (QST(L) = {Phi}ST (L)) whereas a relatively small number of paired locations was under the divergent selection (QS T(L) > {Phi}ST (L)). The comparison for the metapopulation generating only a single trend of QST (P) > {Phi}ST (P) is, therefore, misleading. For conservation, the genetically deficit locations (QST (L) < {Phi}ST (L) and QST (L) = {Phi}ST (L)) of B. serrata warrant for reinforcement of their genetic diversity by introduction of genotypes from other genetically divergent locations (QST (L) > {Phi}ST (L)), which would check the fragmentation and genetic drift, resulting in reproductive vigour, natural regeneration and reverse the endangered status of the species.

genetics↗