Biology subjects

Joshi, A.

Publications and source records attributed to Joshi, A..

At least 109 records · Page 6Linked to original sources

bioRxiv2020

Comprehensive analysis of epigenetic signatures of human transcription control

Advances in sequencing technologies have enabled exploration of epigenetic and transcription profiles at a genome-wide level. The epigenetic and transcriptional landscape is now available in hundreds of mammalian cell and tissue contexts. Many studies have performed multi-omics analyses using these datasets to enhance our understanding of relationships between epigenetic modifications and transcription regulation. Nevertheless, most studies so far have focused on the promoters/enhancers and transcription start sites, and other features of transcription control including exons, introns and transcription termination remain under explored. We investigated interplay between epigenetic modifications and diverse transcription features using the data generated by the Roadmap Epigenomics project. A comprehensive analysis of histone modifications, DNA methylation, and RNA-seq data of about thirty human cell lines and tissue types, allowed us to confirm the generality of previously described relations, as well as to generate new hypotheses about the interplay between epigenetic modifications and transcript features. Importantly, our analysis included previously under-explored features of transcription control namely, transcription termination sites, exon-intron boundaries, middle exons and exon inclusion ratio. We have made the analyses freely available to the scientific community at joshiapps.cbu.uib.no/perepigenomics_app/ for easy exploration, validation and hypotheses generation.

bioinformatics↗

bioRxiv2020

APPLICATION OF GOOD AGRICULTURAL PRACTICES (GAP) BY THE BANANA FARMERS OF CHITWAN, NEPAL

The study was conducted to identify the cultivation practices followed by the banana growers and compares it with the framework of Good Agricultural Practices as recommended by the World Banana Forum. Both qualitative and quantitative approach was used for data collection. The scheduled interview was carried out from 103 banana growers, two focused group discussion was carried out with the banana growers, and two key informant interview was carried out; one with the President of Banana Growers Association, Chitwan and another with Executive Director of Chamber of Commerce and Industry, Chitwan. The findings revealed that GAP related to soil management and fertilization (87.4%) and harvesting and on-farm processing (94.2%) is adopted at a low level. Only 36% of farmers apply an appropriate dose of chemical fertilizer, 28% follow crop rotation and 7.8% perform mulching/ intercropping. About 38% of the respondents do not have any source of irrigation. About 98% of the farmers do not perform any processing, cleaning, storing, and packaging of banana. Further, 55% of farmers do not use appropriate personal protective equipment while applying pesticides. The results showed that there is low awareness regarding GAP among the banana farmers in the Chitwan district. Therefore, the conduction of awareness programs and training related to GAP is recommended. By far, no study has been carried out to analyze the good agricultural practices applied by banana growers in Nepal. This study identified the prevailing gap in farmers practices and good agricultural practices.

plant biology↗

bioRxiv2020

Phylogenetic Analysis of the Novel Coronavirus Reveals Important Variants in Indian Strains

Recently classified as a pandemic by WHO, novel Corononavirus 2019 has affected almost every corner of the globe causing human deaths in a range of hundred thousands. The virus having its roots in Wuhan (China) has been spread over the world by its own property to change itself accordingly. These changes correspond to its transmission and pathogenicity due to which the concept of social distancing appeared into the picture. In this paper, a few findings from the whole genome sequence analysis of viral genome sequences submitted from India are presented. The data used for analysis comprises 440 collective genome sequences of virus submitted in GenBank, GISAID, and SRA projects, from around the world as well as 28 viral sequences from India. Multiple sequence alignment of all genome sequences was performed and analysed. A novel non-synonymous mutation 4809C>T (S1515F) in NSP3 gene of SARS-CoV2 Indian strains is reported along with other frequent and important changes from around the world: 3037C>T, 14408C>T, and 23403A>G. The novel change was observed in samples collected in the month of March, whereas was found to be absent in samples collected in January with the respective persons travel history to China. Phylogenetic analysis clustered the sequences with this change as one separate clade. Mutation was predicted as stabilising change by insilco tool DynaMut. A second patient in the world to our knowledge with multiple (Wuhan and USA) strain contraction was observed in this study. The infected person is among the two early infected patients with travel history to China. Strains sequenced in Iran stood out to have different variants, as most of the reported frequent variants were not observed. The objective of this paper is to highlight the similarities and changes observed in the submitted Indian viral strains. This helps to keep track on the activity, that how virus is changing into a new subtype. Major strains observed were European with the novel change in India and other being emergent clade of Iran. Its important to observe the changes in NSP3 gene, as this gene has been reported with extensive positive selection as well as potential drug target. Extensive Positive Selection Drives the Evolution of Nonstructural Proteins. With the limited number of sequences this was the only frequent novel non-synonymous change observed from Indian strains, thereby making this change vulnerable for investigation in future. This paper has a special focus on tracking of Indian viral sequences submitted in public domain.

bioinformatics↗

bioRxiv2020

Consumption of a high energy density diet triggers microbiota dysbiosis, hepatic lipidosis, and microglia activation in the nucleus of the solitary tract in rats.

Obesity is a multifactorial chronic inflammatory disease. Consumption of high energy density (ED) diets is associated with hyperphagia, increased body weight and body fat accumulation, and obesity. Our lab has previously shown that short-term (4 weeks) consumption of a high ED diet triggers gut microbiota dysbiosis, gut inflammation, and reorganization of the gut-brain vagal communication. The aim of the current study was to investigate the effect of long-term (6 months) consumption of high ED diet on body composition, gut microbiome, hepatocellular lipidosis, microglia activation in the Nucleus of the Solitary Tract, and the development of systemic inflammation. Male Sprague-Dawley rats were fed a low ED diet (5% fat) for two weeks and then switched to a high ED (45% fat) diet for 26 weeks. Twenty-four hour food intake, body weight, and body composition were measured twice a week. Blood serum and fecal samples were collected at baseline, and 1, 4, 8, and 26 weeks after introduction of the high ED diet. Serum samples were used to measure insulin, leptin, and inflammatory cytokines using Enzyme-linked Immunosorbent Assay. Fecal samples were used for 16S rRNA genome sequencing. High ED diet induced microbiota dysbiosis within a week of introducing the diet. In addition, there was significant microglia activation in the intermediate NTS and marked hepatic lipidosis after four weeks of high ED diet. We further observed changes in the serum cytokine profile after 26 weeks of high ED feeding. These data suggest that microbiota dysbiosis is the first response of the organism to high ED diets and this, in turn, detrimentally affects liver fat accumulation, microglia activation in the brain, and circulating levels of inflammatory markers.

physiology↗

bioRxiv2020

LC/MS-QToF Profiling, Anti-Diabetic and Anti-Adipogenic potential of Divya MadhuKalp: A Novel Herbo-mineral Formulation

The incidence rate of diabetes mellitus is increasing worldwide. Herbal formulations have recently gained importance as an alternative therapeutic option in controlling diabetes without causing any side effects. In the present study, we have demonstrated maintenance of glycemic homeostasis and anti-adipogenic potential of a herbo-mineral formulation Divya MadhuKalp (DMK). Initially, we evaluated the presence of bioactive compounds in DMK using LC/MS-QToF analysis. In-vitro analysis of DMK in L6 (skeletal muscle) cells showed a significant increase in cellular glucose uptake. Similarly, a human equivalent dose of DMK significantly reduced blood glucose level in normoglycemic and oral glucose tolerance rat model. DMK extract also inhibited formation of advanced glycation end product and showed anti--glucosidase activity. Further analysis of DMK in 3T3 L1 pre-adipocytes demonstrated anti-adipogenic activity through reduction in intracellular lipid accumulation and triglyceride contents along with downregulation of major adipogenic transcriptional factors (PPAR-{gamma} and C/EBP) and, adipocytes marker genes (LPL, AP2 and adiponectin). In conclusion, DMK exhibited anti-diabetic and anti-adipogenic activities by synergistic effect of its bioactive compounds and can be considered as a potent herbo-mineral formulation for treating metabolic diseases.

cell biology↗

bioRxiv2020

Cellular internalization of Godanti Bhasma (anhydrous CaSO4) induces massive cytoplasmic reversible vacuolation and survival response of mammalian cells.

Bhasmas are Ayurvedic herbo-mineral formulations that have been used since ancient times for therapeutic benefits. Godanti Bhasma (GB) is an anhydrous calcium sulfate preparation processed by heating of gypsum powder with herbal extracts. Thermo-transformation of gypsum into the anhydrous GB was confirmed by Raman and FT-IR spectroscopy. GB particle showed size range of 0.5-5 {micro}m and neutral surface charge. Exposure to mammalian cells with GB particles showed massive vacuolation in their cytoplasm. Interestingly, no vacuolation was observed with parent gypsum particle. The result indicated that the cytoplasmic vacuolation by GB was due to its unique physicochemical property obtained during the thermo-transformation of gypsum. Using lysosomal inhibitors Bafilomycin A1 (BFA1) and Chloroquine (CQ), the process of vacuole formation was suppressed indicating GB induced vacuolation require acidic environment. The GB induced vacuolation was also found to follow dose and time dependent manner. Vacuolation often accompany with the sign of cell death whereas, in our study, massive vacuolation by GB did not induce any cell death. Moreover, GB treated cells survive with massive vacuolar process, which was reversed following post-treatment with vacuole inhibitors in GB treated cells, suggesting normal vacuolar function is essential for cell survival. Treatment of cells with GB was also found to induce translocation of LC3 protein from the nucleus to vacuolar membrane, indicating LC3 associated phagocytosis (LAP) is involved in the vacuolar process. Interestingly, the LAP function was found to be reversed in the cells treated with vacuole inhibitors. Our results provide a mechanistic correlation with GB induced vacuolation and associated LAP function, essential for cell survival. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=164 SRC="FIGDIR/small/930594v3_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@169ed89org.highwire.dtl.DTLVardef@169c339org.highwire.dtl.DTLVardef@900004org.highwire.dtl.DTLVardef@1f13823_HPS_FORMAT_FIGEXP M_FIG C_FIG

cell biology↗

bioRxiv2020

Sleep-like behavior is a fundamental property of the tripartite synapse

The tripartite synapse, consisting of the presynaptic neuron, post-synaptic neuron, and an astrocyte, is considered to be the main locus of signaling between neurons in the brain.1,2 Neurotransmission is energetically very expensive3,4, and the primary neurotransmitter utilized for signaling is glutamate. It has been found that glutamate is also used as a substrate for energy generation.5,6 However, it is unclear what the relationship is between energy generation and availability of neurotransmitter during glutamatergic neurotransmission. Here we show that availability of energy, represented by adenosine triphosphate (ATP), and glutamate for neurotransmission are intimately related, and in fact determine the ability to signal at the tripartite synapse. Using a novel neurochemical mathematical model of the tripartite synapse, we found that glutamate concentrations for neurotransmission and ATP concentrations were interdependent, and their interplay controlled the firing pattern of the presynaptic terminal, as defined by synaptic vesicle release. Furthermore, we found that depending on the parameters chosen in the model, the tripartite synapse demonstrated behavior with limit cycles, alternating between high- and low-frequency firing rates. Our results show that complex behavior with high- and low-activity states, qualitatively meeting the characteristics of sleep7 emerges directly from the nature of the tripartite synapse, with glutamate and ATP concentrations serving as the signals for state changes. We anticipate that our model will serve as a starting point to further elucidate the energetics of neuronal and brain functioning, and eventually shed light on the fundamental question of the nature and necessity of sleep.

neuroscience↗

bioRxiv2019

Salt-free fractionation of complex isomeric mixtures of glycosaminoglycan oligosaccharides compatible with ESI-MS and microarray analysis

Heparin and heparan sulfate (Hp/HS) are linear complex glycosaminoglycans which are involved in diverse biological processes. The structural complexity brings difficulties in separation, making the study of structure-function relationships challenging. Here we present a separation method for Hp/HS oligosaccharide fractionation with cross-compatible solvent and conditions, combining size exclusion chromatography (SEC), ion-pair reversed phase chromatography (IPRP), and hydrophilic interaction chromatography (HILIC) as three orthogonal separation methods that do not require desalting or extensive sample handling. With this method, the final eluent is suitable for structure-function relationship studies, including tandem mass spectrometry and microarray printing. Our data indicate that high resolution is achieved on both IPRP and HILIC for Hp/HS isomers. In addition, the fractions co-eluted in IPRP could be further separated by HILIC, with both separation dimensions capable of resolving some isomeric oligosaccharides. We demonstrate this method using both unpurified reaction products from isomeric synthetic hexasaccharides and an octasaccharide fraction from enoxaparin, identifying isomers resolved by this multi-dimensional separation method. We demonstrate both structural analysis by MS, as well as functional analysis by microarray printing and screening using a prototypical Hp/HS binding protein: basic-fibroblast growth factor (FGF2). Collectively, this method provides a strategy for efficient Hp/HS structure-function characterization.

biochemistry↗

bioRxiv2019

The mitochondrial HSP90 paralog TRAP1 forms an OXPHOS-regulated tetramer and is involved in maintaining mitochondrial metabolic homeostasis

BackgroundThe molecular chaperone TRAP1, the mitochondrial isoform of cytosolic HSP90, remains poorly understood with respect to its pivotal role in the regulation of mitochondrial metabolism. Most studies have found it to be an inhibitor of mitochondrial oxidative phosphorylation (OXPHOS) and an inducer of the Warburg phenotype of cancer cells. However, others have reported the opposite and there is no consensus on the relevant TRAP1 interactors. This calls for a more comprehensive analysis of the TRAP1 interactome and of how TRAP1 and mitochondrial metabolism mutually affect each other.\n\nResultsWe show that the disruption of the gene for TRAP1 in a panel of cell lines dysregulates OXPHOS by a metabolic rewiring that induces the anaplerotic utilization of glutamine metabolism to replenish TCA cycle intermediates. Restoration of wild-type levels of OXPHOS requires full-length TRAP1. Whereas the TRAP1 ATPase activity is dispensable for this function, it modulates the interactions of TRAP1 with various mitochondrial proteins. Quantitatively by far the major interactors of TRAP1 are the mitochondrial chaperones mtHSP70 and HSP60. However, we find that the most stable stoichiometric TRAP1 complex is a TRAP1 tetramer, whose levels change in response to both a decline or an increase in OXPHOS.\n\nConclusionsOur work provides a roadmap for further investigations of how TRAP1 and its interactors such as the ATP synthase regulate cellular energy metabolism. Our results highlight that TRAP1 function in metabolism and cancer cannot be understood without a focus on TRAP1 tetramers as potentially the most relevant functional entity.

cell biology↗

bioRxiv2019

Does Long-Term Selection for Development Time Result in Canalization: A Test Using Drosophila melanogaster

Canalization denotes the robustness of a trait against genetic or environmental perturbation. Plasticity, in contrast indicates the environmental sensitivity of a trait. Stabilizing selection is thought to increase canalization of a trait, whereas directional selection is often thought to lead to decanalization. However, the relationship between selection, canalization and plasticity remains largely unclear. Experimental evolution is a powerful approach for addressing fundamental questions in evolution. Here, we ask whether long-term directional selection for reduced pre-adult development time in Drosophila melanogaster results in the evolution of increased canalization for development time, the trait under primary selection. We additionally investigate whether pre-adult survivorship, a trait only secondarily under selection in this experimental regime, also evolves to become canalized. We examine canalization both in terms of stability of population means and of within population variability across two environmental axes. We used four large outbred populations of D. melanogaster selected for rapid pre-adult development and early reproduction for 295 generations, and four corresponding ancestral control populations that were not under conscious selection for development time or early reproduction. The selected populations had evolved 25% reduction in both development time and pre-adult survivorship at the time of this study. We studied development time and pre-adult survivorship of the selected populations and controls across various combinations ofrearing temperature and larval density. Development time in the selected populations had become more canalized than controls with regard to density, but not temperature. Canalization of development time across density appears to have evolved due to evolutionary changes in the lifehistory and physiology of the selected populations. Pre-adult survivorship, only a secondary correlate of fitness in the selected populations, did not show any clear trend in terms of canalization with regard to either density or temperature, and, overall variation in the trait was greater compared to development time within and across environments. Whether long-term directional selection canalizes or not, therefore, appears to be dependent in a complex way on specific interactions of trait, selection regime and environmental factor in the context of the ecology and physiology of the popualtions under study.

evolutionary biology↗

bioRxiv2018

The sensitivity to Hsp90 inhibitors of both normal and oncogenically transformed cells is determined by the equilibrium between cellular quiescence and activity

The molecular chaperone Hsp90 is an essential and highly abundant central node in the interactome of eukaryotic cells. Many of its large number of client proteins are relevant to cancer. A hallmark of Hsp90-dependent proteins is that their accumulation is compromised by Hsp90 inhibitors. Combined with the anecdotal observation that cancer cells may be more sensitive to Hsp90 inhibitors, this has led to clinical trials aiming to develop Hsp90 inhibitors as anti-cancer agents. However, the sensitivity to Hsp90 inhibitors has not been studied in rigorously matched normal versus cancer cells, and despite the discovery of important regulators of Hsp90 activity and inhibitor sensitivity, it has remained unclear, why cancer cells might be more sensitive. To revisit this issue more systematically, we have generated an isogenic pair of normal and oncogenically transformed NIH-3T3 cell lines. Our proteomic analysis of the impact of three chemically different Hsp90 inhibitors shows that these affect a substantial portion of the oncogenic program and that indeed, transformed cells are hypersensitive. Targeting the oncogenic signaling pathway reverses the hypersensitivity, and so do inhibitors of DNA replication, cell growth, translation and energy metabolism. Conversely, stimulating normal cells with growth factors or challenging their proteostasis by overexpressing an aggregation-prone sensitizes them to Hsp90 inhibitors. Thus, the differential sensitivity to Hsp90 inhibitors may not stem from any particular intrinsic difference between normal and cancer cells, but rather from a shift in the balance between cellular quiescence and activity.

cancer biology↗

bioRxiv2018

Causal gene regulatory network inference using enhancer activity as a causal anchor

MotivationTranscription control plays a crucial role in establishing a unique gene expression signature for each of the hundreds of mammalian cell types. Though gene expression data has been widely used to infer the cellular regulatory networks, the methods mainly infer correlations rather than causality. We propose that a causal inference framework successfully used for eQTL data can be extended to infer causal regulatory networks using enhancers as causal anchors and enhancer RNA expression as a readout of enhancer activity.\n\nResultsWe developed statistical models and likelihood-ratio tests to infer causal gene regulatory networks using enhancer RNA (eRNA) expression information as a causal anchor and applied the framework to eRNA and transcript expression data from the FANTOM consortium. Predicted causal targets of transcription factors (TFs) in mouse embryonic stem cells, macrophages and erythroblastic leukemia overlapped significantly with experimentally validated targets from ChIP-seq and perturbation data. We further improved the model by taking into account that some TFs might act in a quantitative, dosage-dependent manner, whereas others might act predominantly in a binary on/off fashion. We predicted TF targets from concerted variation of eRNA and TF and target promoter expression levels within a single cell type as well as across multiple cell types. Importantly, TFs with high-confidence predictions were largely different between these two analyses, demonstrating that variability within a cell type is highly relevant for target prediction of cell type specific factors. Finally, we generated a compendium of high-confidence TF targets across diverse human cell and tissue types.\n\nAvailabilityMethods have been implemented in the Findr software, available at https://github.com/lingfeiwang/findr\n\nContactTom.Michoel@roslin.ed.ac.uk, Anagha.Joshi@roslin.ed.ac.uk

bioinformatics↗

bioRxiv2018

ERBB2 and KRAS Alterations Mediate Response to EGFR Inhibitors in early stage Gallbladder Cancer

The uncommonness of gallbladder cancer has contributed to the generally poor understanding of the disease, with scant reports restricted to advance-stage tumors. Here, using an integrated analysis of whole exome and phospho-proteome, we show recurrent activating ERBB2 and KRAS somatic mutations are present in 6 and 3 of 44 early-stage rare gallbladder tumors, respectively. In vitro and in vivo cell-based and biochemical assays reveal an essential role of ErbB pathway activation for the survival of gallbladder cells. Interestingly, the genetic and pharmacological dependencies of gallbladder cells are dependent on the KRAS mutant allele status, reminiscent of the clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer. In overall, we present the first evidence that the presence of KRAS (G12V), but not KRAS (G13D) mutation, may preclude gallbladder cancer patients to respond to anti-EGFR treatment, leading to an early adoption of an approved treatment regimen for gallbladder cancer patients.

cancer biology↗

bioRxiv2017

Understanding The Dynamics Of Laboratory Populations Of Drosophila melanogaster: Long-Term Experiments Meet Individual-Based Modelling

The dynamics of stage-structured populations facing variability in resource availability and/or demographic factors like unequal sex-ratios, remains poorly understood. We addressed these issues using a stage-structured individual-based model that incorporates life-history parameters common to many holometabolous insects. The model was calibrated using time series data from a 49-generation experiment on laboratory populations of Drosophila melanogaster, subjected to four different combinations of larval and adult nutritional levels. The model was able to capture multiple qualitative and quantitative aspects of the empirical time series across three independent studies. We then simulated the model to explore the interaction of various life-history parameters and nutritional levels in determining population stability. In all nutritional regimes, stability of the populations was reduced upon increasing egg-hatchability, critical mass and proportion of body resource allocated to female fecundity. However, the stability-effects of increasing sensitivity of female-fecundity to adult density varied across nutrition regimes. The effects of unequal sex-ratio and sex-specific culling were greatly influenced by fecundity but not by levels of juvenile nutrition. Finally, we investigated the implications of some of these insights on the efficiency of the widely-used pest control method, Sterile Insect Technique (SIT). We show that increasing the amount of juvenile food had no effects on SIT efficiency when the density-independent fecundity is low, but reduces SIT efficiency when the density-independent fecundity is high.

ecology↗

bioRxiv2017

Meta-Analysis Of Liver Transcriptomic Data To Identify Mammalian Functional Orthologs

Functional annotation transfer across multi-gene family orthologs can lead to functional misannotations. We hypothesised that co-expression network will help predict functional orthologs amongst complex homologous gene families. To explore the use of transcriptomic data available in public domain to identify functionally equivalent ones from all predicted orthologs, we collected genome wide expression data in mouse and rat liver from over 1500 experiments with varied treatments. We used a hyper-graph clustering method to identify clusters of orthologous genes co-expressed in both mouse and rat. We validated these clusters by analysing expression profiles in each species separately, and demonstrating a high overlap. We then focused on genes in 18 homology groups with one-to-many or many-to-many relationships between two species, to discriminate between functionally equivalent and non-equivalent orthologs. Finally, we further applied our method by collecting heart transcriptomic data (over 1400 experiments) in rat and mouse to validate the method in an independent tissue.

bioinformatics↗

bioRxiv2017

Effects of Social Organization, Trap Arrangement and Density, Sampling Scale, and Population Density on Bias in Population Size Estimation Using Some Common Mark-Recapture Estimators

Mark-recapture estimators are commonly used for population size estimation, and typically yield unbiased estimates for most solitary species with low to moderate home range sizes. However, these methods assume independence of captures among individuals, an assumption that is clearly violated in social species that show fission-fusion dynamics, such as the Asian elephant. In the specific case of Asian elephants, doubts have been raised about the accuracy of population size estimates. More importantly, the potential problem for the use of mark-recapture methods posed by social organization in general has not been systematically addressed. We developed an individual-based simulation framework to systematically examine the potential effects of type of social organization, as well as other factors such as trap density and arrangement, spatial scale of sampling, and population density, on bias in population sizes estimated by POPAN, Robust Design, and Robust Design with detection heterogeneity. In the present study, we ran simulations with biological, demographic and ecological parameters relevant to Asian elephant populations, but the simulation framework is easily extended to address questions relevant to other social species. We collected capture history data from the simulations, and used those data to test for bias in population size estimation. Social organization significantly affected bias in most analyses, but the effect sizes were variable, depending on other factors. Social organization tended to introduce large bias when trap arrangement was uniform and sampling effort was low. POPAN clearly outperformed the two Robust Design models we tested, yielding close to zero bias if traps were arranged at random in the study area, and when population density and trap density were not too low. Social organization did not have a major effect on bias for these parameter combinations at which POPAN gave more or less unbiased population size estimates. Therefore, the effect of social organization on bias in population estimation could be removed by using POPAN with specific parameter combinations, to obtain population size estimates in a social species.

ecology↗

bioRxiv2017

Niche construction in evolutionary theory: the construction of an academic niche?

In recent years, fairly far-reaching claims have been repeatedly made about how niche construction, the modification by organisms of their environment, and that of other organisms, represents a vastly neglected phenomenon in ecological and evolutionary thought. The proponents of this view claim that the niche construction perspective greatly expands the scope of standard evolutionary theory and that niche construction deserves to be treated as a significant evolutionary process in its own right, almost at par with natural selection. Claims have also been advanced about how niche construction theory represents a substantial extension to, and re-orientation of, standard evolutionary theory, which is criticized as being narrowly gene-centric and ignoring the rich complexity and reciprocity of organism-environment interactions. We examine these claims in some detail and show that they do not stand up to scrutiny. We suggest that the manner in which niche construction theory is sought to be pushed in the literature is better viewed as an exercise in academic niche construction whereby, through incessant repetition of largely untenable claims, and the deployment of rhetorically appealing but logically dubious analogies, a receptive climate for a certain sub-discipline is sought to be manufactured within the scientific community. We see this as an unfortunate, but perhaps inevitable, nascent post-truth tendency within science.

evolutionary biology↗

bioRxiv2016

Contribution of mobile elements to the uniqueness of human genome with more than 15,000 human-specific insertions

Mobile elements (MEs) collectively constituted to at least 51% of the human genome. Due to their past incremental accumulation and ongoing DNA transposition of members from certain subfamilies, MEs serve as a significant source for both inter- and intra-species genetic diversity during primate and human evolution. Since MEs can exert direct impact on gene function via a plethora of mechanism, it is believed that the ME-derived genetic diversity has contributed to the phenotypic differences between human and non-human primates, as well as among human populations and individuals. To define the specific contribution of MEs in making Human sapiens as a biologically unique species, we aim to compile a complete list of MEs that are only uniquely present in the human genome, i.e., human-specific MEs (HS-MEs).\n\nBy making use of the most recent reference genome sequences for human and many other primates and a unbiased more robust and integrative multi-way comparative genomic approach, we identified a total of 15,463 HS-MEs. This list of HS-MEs represents a 120% increase from prior studies with over 8,000 being newly identified as HS-MEs. Collectively, these ~15,000 HS-MEs have contributed to a total of 15 million base pair (Mbp) sequence increase through insertion, generation of target site duplications, and transductions, as well as a 0.5 Mbp sequence loss via insertion- mediated deletions, leading to a net total of 14.5 Mbp genome size increase. Other new observations made with these HS-MEs include: 1) identification of several additional ME subfamilies with significant transposition activities not visible with prior smaller datasets (e.g. L1HS, L1PA2, and HERV-K); 2) A clear similarity of the retrotransposition mechanism among L1, Alus, and SVAs that is distinct from HERVs based on the pre- integration site sequence motifs; 3) Y-chromosome as a strikingly hot target for HS-MEs, particularly for LTRs, which showed an insertion rate 15 times higher than the genome average; 4) among the ME types, SVAs seem to show a very strong bias in inserting into existing SVAs. Among the HS-MEs, more than 8,000 elements were integrated into the vicinity of ~4900 unique genes, in regions including CDS, untranslated exon regions, promoters, and introns of protein coding genes, as well as promoters and exons of non- coding RNAs. In seven cases, MEs participate in protein coding. Furthermore, 1,213 HS-MEs contributed to a total of 3,124 experimentally identified binding sites for 146 of the 161 transcriptional factors in association with 622 genes. All these data suggest that these HS-MEs, despite being very young, already showed sufficient sign for their participation in gene function via regulation of transcription, splicing, and protein coding, with more potential for future participation.\n\nIn conclusion, our results demonstrate that the amount of MEs uniquely occurred in the human genome is much higher than previously known, and we predict that the same is true regarding their impact on human genome evolution and function. The comprehensive list of HS-MEs provides an important reference resource for studying the impact of DNA transposition in human genome evolution and gene function.

evolutionary biology↗