Biology subjects

Rastogi, A.

Publications and source records attributed to Rastogi, A..

17 recordsLinked to original sources

bioRxiv2026

A comparative brain atlas of Mexican cavefish identifies naturally-occurring changes in cellular composition and gene expression

Understanding how naturally occurring genetic variation shapes human health and disease is critical for improving diagnosis and treatment strategies. The Mexican cavefish, Astyanax mexicanus, represents a powerful system for evolutionary medicine, enabling investigation of naturally evolved mechanisms of resilience to disease-related traits including diabetes, obesity, insomnia, and eye loss. Larval A. mexicanus, like zebrafish, are transparent, allowing whole-brain imaging, circuit mapping, and the generation of computationally derived atlases that precisely quantify neuroanatomical differences between surface and cave populations. Developing a molecular map of brain cell types provides a foundation for identifying evolved differences in neural circuits and physiology. Here, we present a single-cell atlas of the larval cavefish brain that reveals widespread divergence in the abundance and molecular signatures of neurons and glia. Our cell type map validates known neuroanatomical differences, including a reduction of the optic tectum and expansion of the pineal gland in cavefish. We uncover substantial changes in multiple glial cell classes that are linked to neural regulation of behavior, including microglia. Analysis of differential gene expression between surface and cavefish microglia revealed enhanced genes associated with synaptic pruning and clearance of neural debris, suggesting cavefish increased microglia activity to shape brain development. We also analyzed cell types that did not classify as canonical neurons or glia and identified notable divergence in transcriptomes and cell composition, including reduced meningeal fibroblasts in cavefish and substantial transcriptional changes related to phototransduction in non-visual photoreceptors within the pineal gland. Together, these findings provide a comprehensive atlas of cell type-specific gene expression differences between A. mexicanus surface and cavefish, establishing a platform for dissecting the molecular and cellular basis of evolved disease resilience in cavefish

evolutionary biology↗

bioRxiv2026

Evolved differences in microglial cell biology between surface and cave populations of Astyanax mexicanus

Microglia govern multiple aspects of brain architecture and function by eliminating dying cells, stimulating neurogenesis, refining neural connections, and orchestrating immune responses. The Mexican tetra, Astyanax mexicanus, is a powerful model system for investigating the evolution of brain function, yet microglia have not been investigated in this system. A. mexicanus exists as surface-dwelling and cave morphotypes with prominent behavioral and physiological differences. Notably, these evolved behavioral and physiological changes in cavefish, including diminished immune response, sleep, circadian rhythms, and sensory processing, are directly linked to known microglial functions. These observations suggest that evolved differences in microglia may shape brain circuitry adaptations in cavefish. Here we develop an experimental toolbox to examine microglial specification, dynamics, and function in A. mexicanus to perform comparative analysis of microglial cell biology between the surface and cave morphotypes. We find that the cave populations show increased numbers of microglia over developmental time relative to their surface counterparts. Microglia in Astyanax rapidly expand in response to inflammatory cues, distinct from microglial responses in the related teleost, zebrafish. Furthermore, lysosomal compartments of microglia in the cave populations exhibit increased enhanced proteolytic activity and reduced pH relative to surface morphotypes. Together, our observations reveal evolved differences in microglial cell biology between surface and cave populations of A. mexicanus and provide a framework to uncover novel neuroimmune mechanisms underlying the remarkable adaptations of A. mexicanus.

evolutionary biology↗

bioRxiv2026

Cave evolution on repeat: reuse of the same genomic regions across lineages but not across traits in Astyanax mexicanus

Similar traits repeatedly evolve across independent populations in response to similar environmental conditions. For many repeatedly evolved traits it is unknown if populations evolve similar traits through the same or different genetic mechanisms. To address this question, we leveraged the Mexican tetra fish, Astyanax mexicanus, which has evolved repeatedly through altering many traits including reduced sleep duration, eye degeneration, and metabolic shifts to accommodate limited nutrient availability. We defined whether shared or independent genetic architecture govern the repeated evolution of sleep loss, increased food consumption, early onset adipose deposition, and eye loss in different evolutionary origins of the cavefish phenotype by using Quantitative Trait Locus (QTL) mapping across three cave x surface F2 mapping populations. We found that, among the traits evaluated, eye loss exhibits the most genetic repeatability, with [~]43% of QTL shared across lineages. Sleep loss and metabolic traits (i.e., feeding, adiposity) were genetically less repeatable, with only [~]25-33% of QTL shared across lineages. Next, we explored whether QTL for metabolism, eye loss, and sleep traits in cavefish co-localize in the cavefish genome and could be inherited together to facilitate potential cavefish adaptation. Although these traits have repeatedly co-evolved in cave populations, we did not find evidence for extensive genetic linkage among them. Overall, we found that genetic repeatability is a common feature in the repeated evolution of cave traits, the extent of genetic repeatability varies across cave traits, and that there is little evidence for widespread co-localization of sleep, eye loss, and metabolic traits within the genome. SummaryIndependent populations that evolve similar traits in response to similar environmental conditions provide us with natural replicates for studying what constrains evolutionary change. Iconic examples of repeated trait evolution often involve repeated mutations in the same genes, suggesting there are limits on the type of genes and mutations that can contribute to phenotypic evolution. Here we conduct a multi-trait, multi-population QTL analysis for similar eye loss, sleep loss and metabolic shifts across two lineages of Astyanax mexicanus. Genetic repeatability is present for most traits, but its extent is highly trait dependent and occurs at the level of genomic regions rather than specific genes, highlighting the mosaic of constraint and flexibility involved in genetic repeatability.

evolutionary biology↗

bioRxiv2025

The claudin-like molecule CLC-3 regulates neuromuscular function in Caenorhabditis elegans by modulating cholinergic signalling

Cell adhesion molecules (CAMs play important roles in neurons, contributing to nervous system development, synapse formation, and activity-dependent plasticity. Claudins, the cell-adhesion molecules known for their roles at tight junctions in epithelial and endothelial cells, remain underexplored in neurons, particularly in vertebrates. In contrast, emerging studies in Caenorhabditis elegans have begun to reveal neuronal functions of claudin-like proteins. However, a systematic analysis of their neuronal expression has not been performed. We conducted a transcriptional reporter screen of all claudin-like genes in C. elegans and identified several candidates with previously unreported neuronal expression, highlighting a broader role of this family in the nervous system. One candidate, clc-3, showed robust expression in head, tail, and ventral cord neurons, with no detectable expression in non-neuronal tissues. Functional analyses of clc-3 mutants revealed increased body-bend amplitude and elevated evoked postsynaptic currents at the cholinergic neuromuscular synapses. Imaging and molecular interaction studies demonstrated that CLC-3 localises to the presynaptic membranes in cholinergic neurons, where it interacts with the actin-binding protein NAB-1 and regulates cholinergic signalling. This presynaptic role of CLC-3 likely contributes to the regulation of sinusoidal movement in C. elegans. Our findings identify CLC-3 as a neuronally expressed claudin that regulates motor system output by influencing synaptic vesicle organization and illustrate how changes in synaptic organization are coupled to whole-animal behaviour.

neuroscience↗

bioRxiv2024

Phylogenetic mapping of sleep loss in wild-caught cavefish

Sleep is an evolutionarily ancient and nearly universal behavior throughout the animal kingdom. Multiple cave-dwelling populations of the Mexican tetra, Astyanax mexicanus, have converged on sleep loss compared to river-dwelling surface fish. However, sleep has not been assessed in the vast majority of the 34 known A. mexicanus cave populations. Moreover, whether cavefish sleep less than surface individuals in their natural habitats is currently unknown. Analyzing the distribution of sleep loss and its relationship with other regressive traits in a phylogenetic framework is critical to inform the selective pressures across the different lineages. We measured sleep and locomotor activity in 15 distinct populations of A. mexicanus, including lineages that are broadly representative of the 34 cavefish populations identified to date. Sleep was drastically reduced in all cave and hybrid populations that were tested. A subset of caves contain hybrid populations of A. mexicanus, which show a broad range of eye and pigmentation phenotypes, yet have evolved near-complete loss of sleep. Mapping behavioral changes onto the phylogeny of A. mexicanus populations revealed that loss of sleep and elevated locomotor activity have evolved at least three times. Analysis of sleep in the wild confirms that the sleep loss phenotype observed in lab-reared fish is also present in the natural environment. Together, these findings reveal deep evolutionary convergence on sleep loss in cavefish and provide evidence for sleep loss as a primary trait contributing to cave adaptation.

evolutionary biology↗

bioRxiv2023

Ontogeny and social context regulate the circadian activity patterns of Lake Malawi cichlids

Activity patterns tend to be highly stereotyped and critical for executing many different behaviors including foraging, social interactions and predator avoidance. Differences in the circadian timing of locomotor activity and rest periods can facilitate habitat partitioning and the exploitation of novel niches. As a consequence, closely related species often display highly divergent activity patterns, raising the possibility that a shift from diurnal to nocturnal behavior, or vice versa, can occur rapidly. In Africas Lake Malawi alone, there are over 500 species of cichlids, which inhabit diverse environments and exhibit extensive phenotypic variation. We have previously identified a substantial range in activity patterns across adult Lake Malawi cichlid species, from strongly diurnal to strongly nocturnal. In many species, including fishes, ecological pressures differ dramatically across life-history stages, raising the possibility that activity patterns may change over ontogeny. To determine if rest-activity patterns change across life stages we compared the locomotor patterns of six Lake Malawi cichlid species. While total rest and activity did not change between early juvenile and adult stages, rest-activity patterns did, with juveniles displaying distinct activity rhythms that are more robust than adults. One distinct difference between juveniles and adults is the emergence of complex social behavior. To determine whether social context is required for activity rhythms, we next measured locomotor behavior in group housed adult fish. We found that when normal social interactions were allowed, locomotor activity patterns were restored, supporting the notion that social interactions promote circadian regulation of activity in adult fish. These findings reveal a previously unidentified link between developmental stage and social interactions in the circadian timing of cichlid activity.

evolutionary biology↗

bioRxiv2022

Changes in functional composition and gene expression in eukaryotic plankton at the Atlantic-Arctic Polar front

In the Arctic Ocean, phytoplankton communities, dominated by eukaryotes, sustain the marine food web and influence biogeochemical cycles. While many are endemic, some are transported by currents from the Atlantic Ocean along an environmental gradient that steepens at the polar front. Despite these distinct biogeographies, the functional characteristics of these communities remain poorly characterized. Here, we analyzed twenty metatranscriptomes from a North Atlantic-Arctic environmental gradient considering ocean currents transport times. Functions related to the regulation of gene expression and cold acclimation were more abundant in Arctic metatranscriptomes. Using the PHATE dimensionality reduction algorithm, reconstructed transcriptomes of Bacillariophyta, Mamiellales, Pelagophyceae, and Phaeocystales revealed different gene expression patterns, including photosynthesis regulation. All groups showed upregulation of numerous key temperature-associated functions and a subset of shared functions, supporting a convergence in transcriptomic changes under polar conditions. This study, based on a new resource of reconstructed transcriptomes, addressed the functional differentiation of eukaryotic phytoplankton across the North Atlantic and Arctic Ocean. It evidenced both differential and convergent changes in gene expression across the polar front in widespread phytoplankton types. These results advance our understanding of the functional dynamics of phytoplankton along environmental gradients.

genomics↗

bioRxiv2021

Secretome of senescent hepatoma cells modulate macrophage polarization and neutrophil extracellular traps formation

Presence of dysfunctional senescent hepatocyte is a hallmark feature of cirrhosis. We now report the presence of senescent hepatocytes (p21 and p53 positive) in vicinity of infiltrated immune cells in hepatocellular carcinoma. Hence, we checked if senescent cells can alter fate of macrophage polarization and neutrophil extracellular trap (NETs) formation. Using an in vitro assay, senescence was induced in hepatoma cells (HepG2 and Huh7 cells) by doxorubicin treatment and senescent cell showed secretory phenotype with strong expression of cytokines (IL1{beta}, IL6, IL8 and IL13) as evaluated by Flow cytometry. The senescent secretome from hepatoma cells induced macrophage differentiation predominantly with M2 markers (CD80, CD86) while that of non-senescent cell induced M1 phenotype (CD163, CD206) as analysed by flow cytometry. Human hepatocellular carcinoma harbouring senescent hepatocytes showed presence of M2 macrophages, while M1 macrophages were predominant in non-tumorous region. Additionally, the senescent secretome from Huh7 cells (p53mut) enhanced the NETs formation, while HepG2 (p53+/+) secretome had an inhibitory affect In conclusion, the "pro-inflammatory" senescent secretome drives non-inflammatory type M2 macrophage polarization and modulate neutrophil traps thereby modulating the microenvironment towards tumor promotion. Targeting senescent hepatocyte secretome appears a promising therapeutic target in liver cancer in future. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/423905v1_ufig1.gif" ALT="Figure 1"> View larger version (27K): org.highwire.dtl.DTLVardef@1df4256org.highwire.dtl.DTLVardef@7c4f53org.highwire.dtl.DTLVardef@13bfe80org.highwire.dtl.DTLVardef@1c1c4b5_HPS_FORMAT_FIGEXP M_FIG Work Highlight (Diagrammatic Representation). C_FIG

cancer biology↗

bioRxiv2020

Troxerutin acts on complement mediated inflammation to ameliorate arthritic symptoms in rats.

Troxerutin (TXR), is a phytochemical reported to possess anti-inflammatory and hepatoprotective effects. In this study, we aimed to exploit anti-arthritic properties of TXR using an adjuvant induced arthritic (AIA) rat model. AIA induced rats showed highest arthritis score at disease onset and by oral administration of TXR (50, 100, 200 mg/kg body weight), reduced to basal level in a dose dependent manner. Isobaric tag for relative and absolute quantitative (iTRAQ) proteomics tool was employed to identify deregulated joint homogenate proteins in AIA and TXR treated rats to decipher probable mechanism of the TXR action in arthritis. iTRAQ analysis identified a set of 434 joint homogenate proteins with 65 deregulated proteins (log2 case/control [≥]1.5) in AIA. Expressions of a set of important proteins (AAT, T-kininogen, vimentin, desmin, and nucleophosmin) that could classify AIA from healthy were validated using Western blot analysis. Western blot data corroborated proteomics findings. In silico protein-protein interaction study of joint homogenate proteome revealed that complement component 9, the major building blocks of the membrane attack complex (MAC) responsible for sterile inflammation, gets perturbed in AIA. Our dosimetry study suggests that a TXR dose of 200 mg/kg body weight for 15 days is sufficient to bring the arthritis score to basal levels in AIA rats. We have shown the importance of TXR as an anti-arthritis agent in AIA model and after additional investigation its arthritis ameliorating properties could be exploited for clinical usability.

biochemistry↗

bioRxiv2020

The neural representation of force across grasp types in motor cortex of humans with tetraplegia

Intracortical brain-computer interfaces (iBCIs) have the potential to restore hand grasping and object interaction to individuals with tetraplegia. Optimal grasping and object interaction require simultaneous production of both force and grasp outputs. However, since overlapping neural populations are modulated by both parameters, grasp type could affect how well forces are decoded from motor cortex in a closed-loop force iBCI. Therefore, this work quantified the neural representation and offline decoding performance of discrete hand grasps and force levels in two participants with tetraplegia. Participants attempted to produce three discrete forces (light, medium, hard) using up to five hand grasp configurations. A two-way Welch ANOVA was implemented on multiunit neural features to assess their modulation to force and grasp. Demixed principal component analysis was used to assess for population-level tuning to force and grasp and to predict these parameters from neural activity. Three major findings emerged from this work: 1) Force information was neurally represented and could be decoded across multiple hand grasps (and, in one participant, across attempted elbow extension as well); 2) Grasp type affected force representation within multi-unit neural features and offline force classification accuracy; and 3) Grasp was classified more accurately and had greater population-level representation than force. These findings suggest that force and grasp have both independent and interacting representations within cortex, and that incorporating force control into real-time iBCI systems is feasible across multiple hand grasps if the decoder also accounts for grasp type. Significance StatementIntracortical brain-computer interfaces (iBCIs) have emerged as a promising technology to potentially restore hand grasping and object interaction in people with tetraplegia. This study is among the first to quantify the degree to which hand grasp affects force-related - or kinetic - neural activity and decoding performance in individuals with tetraplegia. The study results enhance our overall understanding of how the brain encodes kinetic parameters across varying kinematic behaviors -- and in particular, the degree to which these parameters have independent versus interacting neural representations. Such investigations are a critical first step to incorporating force control into human-operated iBCI systems, which would move the technology towards restoring more functional and naturalistic tasks.

neuroscience↗

bioRxiv2020

Human iPSC-derived cerebral organoids model features of Leigh Syndrome and reveal abnormal corticogenesis

Leigh syndrome (LS) is a rare, inherited neurometabolic disorder that presents with bilateral brain lesions, caused by defects in the mitochondrial respiratory chain and associated nuclear-encoded proteins. We generated iPSCs from three patient-derived LS fibroblast lines and identified, by whole-exome and mitochondrial sequencing, unreported mutations in pyruvate dehydrogenase (GM0372, PDH; GM13411, MT-ATP6/PDH) and dihydrolipoyl dehydrogenase (GM01503, DLD). LS-derived iPSC lines were viable and generally capable of differentiating into key progenitor populations, but we identified several abnormalities in three-dimensional differentiation models of brain development. LS-derived cerebral organoids showed defects in neural epithelial bud generation, size, and cortical architecture at 100 days. The double mutant MT-ATP6/PDH line produced organoid neural progenitor cells with abnormal mitochondrial morphology characterized by fragmentation and disorganization and showed an increased generation of astrocytes. These studies aim to provide a comprehensive phenotypic characterization of available patient-derived cell lines that can be used as LS model systems.

cell biology↗

bioRxiv2020

Blunted Diurnal Firing in Lateral Habenula Projections to Dorsal Raphe Nucleus and Delayed Photoentrainment in Stress-Susceptible Mice.

Daily rhythms are disrupted in patients suffering from mood disorders. The lateral habenula (LHb) and dorsal raphe nucleus (DRN) contribute to circadian timekeeping and regulate mood. Thus, pathophysiology in these nuclei may be responsible for aberrations in daily rhythms during mood disorders. Using the chronic social defeat stress (CSDS) paradigm and in-vitro slice electrophysiology we measured the effects of stress on diurnal rhythms in firing of LHb cells projecting to the DRN (cellsLHb[->]DRN) and DRN cells alone. We also performed optogenetic experiments to investigate if increased firing in cellsLHb[->]DRN during exposure to subthreshold social defeat stress (SSDS), induces stress-susceptibility. Last we investigated whether exposure to CSDS affected the ability of mice to phototentrain to a new LD cycle. The cellsLHb[->]DRN and DRN cells alone of stress-susceptible mice express greater blunted diurnal firing compared to stress-naive (control) and stress-resilient mice. Day-time optogenetic activation of cellsLHb[->]DRN during SSDS induces stress-susceptibility which shows the direct correlation between increased activity in this circuit and putative mood disorders. Finally, we found that stress-susceptible mice are slower, while stress-resilient mice are faster, at photoentraining to a new LD cycle. Our findings suggest that CSDS induces blunted daily rhythms in firing in cellsLHb[->]DRN and slow rate of photoentrainment in susceptible-mice. In contrast, resilientmice may undergo homeostatic adaptations that maintain daily rhythms in firing in cellsLHb[->]DRN and also show rapid photoentrainment to a new LD-cycle.

neuroscience↗

bioRxiv2019

H3K27me3 natural variation selectively marks genes predicted to be important for differentiation in unicellular algae

O_LIIn multicellular organisms, Polycomb Repressive Complex2 (PRC2) is known to deposit H3K27me3 to establish and maintain gene silencing, critical for developmentally regulated processes. PRC2 complex is absent in both widely studied model yeasts which initially suggested that PRC2 arose with the emergence of multicellularity. However, its discovery in several unicellular species including microalgae questions its role in unicellular eukaryotes. C_LIO_LIHere, we use Phaeodactylum tricornutum enhancer of zeste E(z) knockouts and show that P. tricornutum E(z) is responsible for di and tri-methylation of lysine 27 of histone H3. C_LIO_LIH3K27me3 depletion abolishes cell morphology in P. tricornutum providing evidence for its role in cell differentiation. Genome wide profiling of H3K27me3 in fusiform and triradiate cells further revealed genes that may specify cell identity. C_LIO_LIThese results suggest a role for PRC2 and its associated mark in cell differentiation in unicellular species and highlight their ancestral function in a broader evolutionary context than is currently appreciated. C_LI

cell biology↗

bioRxiv2019

Evaluation of CD8 T cell killing models with computer simulations of 2-photon imaging experiments

In vivo imaging of cytotoxic T lymphocyte (CTL) killing activity revealed that infected cells have a higher observed probability of dying after multiple contacts with CTLs, suggesting memory effect in CTLs or infected cells. We developed a three-dimensional agent-based model of CTL killing activity to discriminate different hypotheses about how infected cells get killed based on quantitative 2-photon in vivo observations. We compared a constant CTL killing probability with mechanisms of signal integration in CTL or infected cells. The most likely scenario implied increased susceptibility of infected cells with increasing number of CTL contacts where the total number of contacts was a critical factor as opposed to signal integration over many contacts. However, when allowing in silico T cells to interact with apoptotic target cells (zombie contacts), a contact history independent killing mechanism was also in agreement with the experimental datasets. We showed that contacts that take place between CTLs and dying infected cells impact the observed killing dynamics because even in absence of modulation of cell properties, we saw an increase of the observed probability of killing infected cells with more interactions. The duration taken by an infected cell to die and the per capita killing rate (PCKR) of CTLs, parameters hard to measure directly, were determined from the model and turned out predictive to distinguish the different CTL killing models in future experiments. The comparison of observed datasets to simulation results, revealed limitations in interpreting 2-photon data, and provided prediction for additional measurements to distinguish CTL killing models. HighlightsO_LIKilling of infected cells by cytotoxic T cells typically involves more than a single contact. C_LIO_LICytotoxic T cells or infected cells integrate signals from multiple interactions. C_LIO_LIT cell contacts with dying infected cells have a major impact on in vivo data interpretation. C_LI Significance StatementDespite having a clear understanding of cytotoxic T lymphocyte (CTL) mediated cytotoxicity mechanisms, the quantitative dynamics remain unexplored at a cellular level. We developed an agent-based model to compare different hypotheses for mechanisms of CTL mediated cytotoxicity that could lead to an increase in observed probability of killing infected cells at higher interactions with CTLs as seen in vivo. We showed that this behaviour can be explained by modulation of properties by infected cells or CTLs with increasing number of contacts. For the modulation, we compared two modes of signal integration and showed that time is not a relevant parameter in signal integration. We also studied the impact of contacts between CTLs and apoptotic infected cells on observed killing properties.

systems biology↗

bioRxiv2019

Assortative mating by population of origin in a mechanistic model of admixture

Populations whose mating pairs have levels of similarity in phenotypes or genotypes that differ systematically from the level expected under random mating are described as experiencing assortative mating. Excess similarity in mating pairs is termed positive assortative mating, and excess dissimilarity is negative assortative mating. In humans, empirical studies suggest that mating pairs from various admixed populations--whose ancestry derives from two or more source populations--possess correlated ancestry components that indicate the occurrence of positive assortative mating on the basis of ancestry. Generalizing a two-sex mechanistic admixture model, we devise a model of one form of ancestry-assortative mating that occurs through preferential mating based on source population. Under the model, we study the moments of the admixture fraction distribution for different assumptions about mating preferences, including both positive and negative assortative mating by population. We consider the special cases of assortative mating by population that involve a single admixture event and that consider a model of constant contributions to the admixed population over time. We demonstrate that whereas the mean admixture under assortative mating is equivalent to that of a corresponding randomly mating population, the variance of admixture depends on the level and direction of assortative mating. In contrast to standard settings in which positive assortment increases variation within a population, certain assortative mating scenarios allow the variance of admixture to decrease relative to a corresponding randomly mating population: with the three populations we consider, the variance-increasing effect of positive assortative mating within a population might be overwhelmed by a variance-decreasing effect emerging from mating preferences involving other pairs of populations. The effect of assortative mating is smaller on the X chromosome than the autosomes because inheritance of the X in males depends only on the mothers ancestry, not on the mating pair. Because the variance of admixture is informative about the timing of admixture and possibly about sex-biased admixture contributions, the effects of assortative mating are important to consider in inferring features of population history from distributions of admixture values. Our model provides a framework to quantitatively study assortative mating under flexible scenarios of admixture over time.

evolutionary biology↗

bioRxiv2017

Continuous gene flow contributes to low global species abundance and distribution of a marine model diatom

Diatoms emerged in the Mesozoic period and presently constitute one of the main primary producers in the worlds ocean and are of a major economic importance. In the current study, using whole genome sequencing of ten accessions of the model diatom Phaeodactylum tricornutum, sampled at broad geospatial and temporal scales, we draw a comprehensive landscape of the genomic diversity within the species. We describe strong genetic subdivisions of the accessions into four genetic clades (A-D) with constituent populations of each clade possessing a conserved genetic and functional makeup, likely a consequence of the limited dispersal of P. tricornutum in the open ocean. We further suggest dominance of asexual reproduction across all the populations, as implied by high linkage disequilibrium. Finally, we show limited yet compelling signatures of genetic and functional convergence inducing changes in the selection pressure on many genes and metabolic pathways. We propose these findings to have significant implications for understanding the genetic structure of diatom populations in nature and provide a framework to assess the genomic underpinnings of their ecological success and impact on aquatic ecosystems where they play a major role. Our work provides valuable resources for functional genomics and for exploiting the biotechnological potential of this model diatom species.

genomics↗

bioRxiv2017

Integrative analysis of large scale transcriptome data draws a comprehensive landscape of Phaeodactylum tricornutum functional genome and evolutionary origin of diatoms

Diatoms are one of the most successful and ecologically important groups of eukaryotic phytoplankton in the modern ocean. Deciphering their genomes is a key step towards better understanding of their biological innovations, evolutionary origins, and ecological underpinnings. Here, we have used 90 RNA-Seq datasets from different growth conditions combined with published expressed sequence tags and protein sequences from multiple taxa to explore the genome of the model diatom Phaeodactylum tricornutum, and introduce 1,489 novel genes. The new annotation additionally permitted the discovery for the first time of extensive alternative splicing (AS) in diatoms, including intron retention and exon skipping which increases the diversity of transcripts to regulate gene expression in response to nutrient limitations. In addition, we have used up-to-date reference sequence libraries to dissect the taxonomic origins of diatom genomes. We show that the P. tricornutum genome is replete in lineage-specific genes, with up to 47% of the gene models present only possessing orthologues in other stramenopile groups. Finally, we have performed a comprehensive de novo annotation of repetitive elements showing novel classes of TEs such as SINE, MITE, LINE and TRIM/LARD. This work provides a solid foundation for future studies of diatom gene function, evolution and ecology.

bioinformatics↗