Biology subjects

Moore, M.

Publications and source records attributed to Moore, M..

54 records · Page 3Linked to original sources

bioRxiv2022

Glioblastoma exosomes influence glial cell hyaluronic acid deposition to promote invasiveness

BackgroundInfiltration of glioblastoma (GBM) throughout the brain leads to its inevitable recurrence following standard-of-care treatments, such as surgical resection, chemo- and radio-therapy. A deeper understanding of the mechanisms invoked by GMB to infiltrate the brain is needed to develop approaches to contain the disease and reduce recurrence. The aim of this study was to discover mechanisms through which extracellular vesicles (EVs) released by GBM influence the brain microenvironment to facilitate infiltration, and to determine how altered extracellular matrix (ECM) deposition by glial cells might contribute to this. MethodsCRISPR was used to delete genes, previously established to drive carcinoma invasiveness and EV production, from patient-derived primary and GBM cell lines. We purified and characterised EVs released by these cells, assessed their capacity to foster pro-migratory microenvironments in mouse brain slices, and evaluated the contribution made by astrocyte-derived extracellular matrix (ECM) to this. Finally, we determined how CRISPR-mediated deletion of genes, which we had found to control EV-mediated communication between GBM cells and astrocytes, influenced GBM infiltration when orthotopically injected into CD1-nude mice. ResultsGBM cells expressing a p53 mutant (p53273H) with established pro-invasive gain-of-function release EVs containing a sialomucin, podocalyxin (PODXL), which encourages astrocytes to deposit ECM with increased levels of hyaluronic acid (HA). This HA-rich ECM, in turn, promotes migration of GBM cells. Consistently, CRISPR-mediated deletion of PODXL opposes infiltration of GBM in vivo. ConclusionsThis work describes several key components of an EV-mediated mechanism though which GBM cells educate astrocytes to support infiltration of the surrounding healthy brain tissue. KEY POINTSThe p53R273H oncogene encourages GBM cells to release EVs containing podocalyxin. Podocalyxin-containing EVs from GBM increase hyaluronic acid production by astrocytes. Hyaluronic acid production by astrocytes drives GBM migration. IMPORTANCE OF THE STUDYThe infiltrative behaviour of glioblastoma (GBM) leads to widespread dissemination of cancer cells throughout the brain. Thus, even following successful resection of the primary tumour these disseminated cells inevitably contribute to post-surgical relapse. In this study, we have discovered a new mechanism through which GBM can release small extracellular vesicles (EVs) to reprogramme extracellular matrix (ECM) production by astrocytes in a way that supports increased invasive behaviour of the GBM cells. Moreover, we have discovered several key components of the pathway which contribute to this EV-mediated GBM-glial cell communication. Principal amongst these, we show that a particular mutant of the p53 tumour suppressor, p53273H drives the release of EVs which foster the deposition of pro-invasive ECM by astrocytes. This study provides mechanistic insight into why brain tumours expressing p53273H are associated with particularly poor patient survival and highlights the possibility of deploying agents which target astrocyte ECM deposition to reduce the morbidity of p53273H- expressing GBM.

cancer biology↗

bioRxiv2021

3D reconstruction of cell nuclei in a full Drosophila brain

We reconstructed all cell nuclei in a 3D image of a Drosophila brain acquired by serial section electron microscopy (EM). The total number of nuclei is approximately 133,000, at least 87% of which belong to neurons. Neuronal nuclei vary from several hundred down to roughly 5 cubic micrometers. Glial nuclei can be even smaller. The optic lobes contain more than two times the number of cells than the central brain. Our nuclear reconstruction serves as a spatial map and index to the cells in a Drosophila brain.

neuroscience↗

bioRxiv2021

Retrograde Control of Cytosolic Translation Targets Synthesis of Plastid Localized Proteins and Nuclear Responses for Efficient Light Acclimation.

Canonical retrograde signalling comprises information transmission from organelles to the nucleus and in particular controls gene expression for organellar proteins. The need to re-assess this paradigm was suggested by discrepancies between de novo protein synthesis and transcript abundance in response to excess light. Here we uncover major components of a translation-dependent retrograde signalling pathway that first impacts translation and then transcription. The response realization depends on the kinases Mitogen-activated protein kinase 6 (MPK6) and Sucrose non-fermenting 1-related kinase (SnRK1) subunit, AKIN10. Global ribosome foot-printing revealed differential ribosome association of 951 transcripts within 10 min after transfer from low to high light. Despite predominant translational repression, 15 % of transcripts were increased in translation and enriched for chloroplast-localized photosynthetic proteins. About one third of these transcripts, including Stress associated proteins (SAP) 2 and 3, share regulatory motifs in their 5'-UTR that act as binding sites for glyceraldehyde-3-phosphate dehydrogenase (GAPC) and light responsive RNA binding proteins (RBPs). SAP2 and 3 are both translationally regulated and interact with the calcium sensor Calmodulin-like 49 (CML49), which promotes relocation to the nucleus inducing a translation-dependent nuclear stress response. Thus, translation-dependent retrograde signalling bifurcates to directly regulate a translational circuit of chloroplast proteins and simultaneously initiate a nuclear circuit synchronizing retrograde and anterograde response pathways, serving as a rapid mechanism for functional acclimation of the chloroplast.

plant biology↗

bioRxiv2021

Dynamics and turnover of memory CD8 T cell responses following yellow fever vaccination

Understanding how immunological memory lasts a lifetime requires quantifying changes in the number of memory cells as well as how their division and death rates change over time. We address these questions by using a statistically powerful mixed-effects differential equations framework to analyze data from two human studies that follow CD8 T cell responses to the yellow fever vaccine (YFV-17D). Models were first fit to the frequency and division rates of YFV-specific memory CD8 T cells 42 days to 1 year post-vaccination. A different dataset, on the loss of YFV-specific CD8 T cells over three decades, was used to assess out of sample predictions of our models. The commonly used exponential and bi-exponential decline models performed relatively poorly. Models with the cell loss following a power law (exactly or approximately) were most predictive. Notably, using only the first year of data, these models accurately predicted T cell frequencies up to 30 years post-vaccination. Our analyses suggest that division rates of these cells drop and plateau at a low level (0.001 per day, ~double estimates for naive T cells) within one year following vaccination, whereas death rates continue to decline for much longer. Our results show that power laws can be predictive for T cell memory, a finding that may be useful for vaccine evaluation and epidemiological modeling. Moreover, since power laws asymptotically decline more slowly than any exponential decline, our results help explain the longevity of immune memory phenomenologically. Author summaryImmunological memory, generated in response to infection or vaccination, may provide complete or partial protection from antigenically similar infections for the lifetime. Memory CD8 T cells are important players in protection from secondary viral infections but quantitative understanding of their dynamics in humans is limited. We analyze data from two studies where immunization with the yellow fever virus vaccine (YFV-17D) generates a mild acute infection and long-term memory. We find that: (i) the division rate of YFV-17D-specific CD8 T cells drops and stabilizes at ~ 0.1% per day during the first year following vaccination whereas the death rate declines more gradually, and (ii) the number of these cells declines approximately in accordance with a power law ({propto}time-0.82) for at least several decades following vaccination.

immunology↗

bioRxiv2020

Capturing in-field root system dynamics with the RootTracker

Optimizing root system architecture offers a promising approach to developing stress tolerant cultivars in the face of climate change, as root systems are critical for water and nutrient uptake as well as mechanical stability. However, breeding for optimal root system architecture has been hindered by the difficulty in measuring root growth in the field. Here, we describe a technology, the RootTracker (RT), which employs capacitance touch sensors to monitor in-field root growth over time. Configured in a cylindrical shutter-like fashion around a planted seed, 264 electrodes are individually charged multiple times over the course of an experiment. Signature changes in the measured capacitance and resistance readings indicate when a root has touched or grown close to an electrode. Using the RootTracker, we have measured root system dynamics of commercial maize hybrids growing in both typical Midwest field conditions and under different irrigation regimes. We observed rapid responses of root growth to water deficits and found evidence for a "priming response" in which an early water deficit causes more and deeper roots to grow at later time periods. There was genotypic variation among hybrid maize lines in their root growth in response to drought, indicating a potential to breed for root systems adapted for different environments.

plant biology↗

bioRxiv2020

Inhibition of the phosphoinositide 3-kinase-AKT-cyclic GMP-c-Jun N-terminal kinase signaling pathway attenuates the development of morphine tolerance in a mouse model of neuropathic pain

BackgroundOpioid management of chronic pain can cause opioid-induced analgesic tolerance and hyperalgesia, complicating clinical pain-management treatments. Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3K{gamma}-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. MethodsMorphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated-JNK levels, cGMP, and gene expression analysis. ResultsGene expression for the PI3K{gamma}-AKT-cGMP-JNK signaling pathway including, Akt1, Akt2, Akt3, Pik3cg, Pten, Jnk3, and nNos1 were decreased in the spinal cord with varied expression changes in the dorsal root ganglia and sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We observed significant increases in total and phosphorylated-JNK levels in the spinal cord, total JNK in dorsal root ganglia, and cGMP in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K, nNOS, or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. ConclusionsOverall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance. Continued research into this pathway will contribute to the development of new analgesic drug therapies.

neuroscience↗

bioRxiv2020

FlyWire: Online community for whole-brain connectomics

Due to advances in automated image acquisition and analysis, new whole-brain connectomes beyond C. elegans are finally on the horizon. Proofreading of whole-brain automated reconstructions will require many person-years of effort, due to the huge volumes of data involved. Here we present FlyWire, an online community for proofreading neural circuits in a fly brain, and explain how its computational and social structures are organized to scale up to whole-brain connectomics. Browser-based 3D interactive segmentation by collaborative editing of a spatially chunked supervoxel graph makes it possible to distribute proofreading to individuals located virtually anywhere in the world. Information in the edit history is programmatically accessible for a variety of uses such as estimating proofreading accuracy or building incentive systems. An open community accelerates proofreading by recruiting more participants, and accelerates scientific discovery by requiring information sharing. We demonstrate how FlyWire enables circuit analysis by reconstructing and analysing the connectome of mechanosensory neurons.

neuroscience↗

bioRxiv2020

Swimming direction of the Glass Catfish, Kryptopterus bicirrhis, is responsive to magnetic stimulation

Several marine species have developed a magnetic perception that is essential for navigation and detection of prey and predators. One of these species is the transparent glass catfish that contains an ampullary organ dedicated to sense magnetic fields. Here we examine the behavior of the glass catfish in response to static magnetic fields which will provide valuable insight on function of this magnetic response. By utilizing state of the art animal tracking software and artificial intelligence approaches, we quantified the effects of magnetic fields on the swimming direction of glass catfish. The results demonstrate that glass catfish placed in a radial arm maze, consistently swim away from magnetic fields over 20 {micro}T and show adaptability to changing magnetic field direction and location.

animal behavior and cognition↗

bioRxiv2020

Nectar-dwelling microbes of common tansy are attractive to its mosquito pollinator, Culex pipiens L.

BackgroundThere is widespread interkingdom signalling between insects and microbes. For example, microbes found in floral nectar may modify its nutritional composition and produce odorants that alter the floral odor bouquet which may attract insect pollinators. Mosquitoes consume nectar and can pollinate flowers. We identified microbes isolated from nectar of common tansy, Tanacetum vulgare, elucidated the microbial odorants, and tested their ability to attract the common house mosquito, Culex pipiens. ResultsWe collected 18 microbial isolates from T. vulgare nectar, representing at least 12 different taxa which we identified with 16S or 26S rDNA sequencing as well as by biochemical and physiological tests. Three microorganisms (Lachancea thermotolerans, Micrococcus lactis, Micrococcus luteus) were grown on culture medium and tested in bioassays. Only the yeast L. thermotolerans grown on nectar, malt extract agar, or in synthetic nectar broth significantly attracted C. pipiens females. The odorant profile produced by L. thermotolerans varied with the nutritional composition of the culture medium. Surprisingly, all three microbes grown separately, but presented concurrently, attracted fewer C. pipiens females than L. thermotolerans by itself. ConclusionsFloral nectar of T. vulgare contains various microbes whose odorants contribute to the odor profile of inflorescences. In addition, L. thermotolerans produced odorants that attract Cx. pipiens females. As the odor profile of L. thermotolerans varied with the composition of the culture medium, we hypothesize that microbe odorants inform nectar-foraging mosquitoes about the availability of certain macro-nutrients which, in turn, affect foraging decisions by mosquitoes.

ecology↗

bioRxiv2019

The a-isoform of VEGFA165 is a Significantly Stronger Activator of Human Retinal Endothelial Cells compared to the b-isoform

PurposeThere are reports that a b-isoform of Vascular Endothelial Growth Factor-A-165 (VEGFA165b) is predominant in normal human vitreous, switching to the a-isoform (VEGFA165a) in the vitreous of some diseased eyes. While these isoforms appear to have a different ability to activate the VEGF-Receptor-2 (VEGFR2) in various endothelial cells, the nature of their ability to activate intracellular signalling pathways is not fully characterized, especially in retinal endothelial cells. We determined their activation potential for two key intracellular signalling pathways (MAPK, AKT) over complete dose-response curves and compared potential effects on the expression of several VEGFA165 target genes in primary human retinal microvascular endothelial cells (HRMECs). MethodsTo determine full dose-response curves for the activation of MAPK (ERK1/2), AKT and VEGFR2, direct in-cell western assays were developed using primary Human Retinal Microvascular Endothelial Cells (HRMECs). Potential differences in dose-response effects on gene expression markers related to endothelial cell / leukocyte adhesion (ICAM1, VCAM1 and SELE) and tight-junctions (CLDN5 and OCLN) were tested by quantitative-PCR. ResultsActivation dose-response analysis revealed much stronger activation of MAPK, AKT and VEGFR2 by the a-isoform at lower doses. MAPK activation in primary HRMECs displayed a sigmoidal dose-response to a range of VEGFA165a concentrations spanning 10-250 pM, which shifted higher into the 100-5,000 pM range with VEGFA165b. Similar maximum activation of MAPK was achieved by both isoforms at high concentration. Maximum activation of AKT by VEGFA165b was only half of the maximum activation from VEGFA165a. At a lower intermediate dose, where VEGFA165a activated intracellular signalling stronger than VEGFA165b, the changes to VEGFA target gene expression was generally greater with VEGFA165a. ConclusionsIn primary HRMECs, VEGFA165a could maximally activate MAPK and AKT at lower concentrations where VEGFA165b had relatively little effect. The timing for maximal activation of MAPK was similar for both isoforms, which is different than reprorted for non-retinal endothelial cells. While VEGFA165a and VEGFA165b are limited to the sequence of their six C-terminal six amino acids, this results in a large difference in their ablility to activate at least two key intracellular signalling pathways and potentially VEGF target gene expression in primary human retinal endothelial cells.

cell biology↗

bioRxiv2019

Disentangling Sources of Gene Tree Discordance in Phylotranscriptomic Datasets: A Case Study from Amaranthaceae s.l.

Gene tree discordance in large genomic datasets can be caused by evolutionary processes such as incomplete lineage sorting and hybridization, as well as model violation, and errors in data processing, orthology inference, and gene tree estimation. Species tree methods that identify and accommodate all sources of conflict are not available, but a combination of multiple approaches can help tease apart alternative sources of conflict. Here, using a phylotranscriptomic analysis in combination with reference genomes, we test a hypothesis of ancient hybridization events within the plant family Amaranthaceae s.l. that was previously supported by morphological, ecological, and Sanger-based molecular data. The dataset included seven genomes and 88 transcriptomes, 17 generated for this study. We examined gene-tree discordance using coalescent-based species trees and network inference, gene tree discordance analyses, site pattern tests of introgression, topology tests, synteny analyses, and simulations. We found that a combination of processes might have generated the high levels of gene tree discordance in the backbone of Amaranthaceae s.l. Furthermore, we found evidence that three consecutive short internal branches produce anomalous trees contributing to the discordance. Overall, our results suggest that Amaranthaceae s.l. might be a product of an ancient and rapid lineage diversification, and remains, and probably will remain, unresolved. This work highlights the potential problems of identifiability associated with the sources of gene tree discordance including, in particular, phylogenetic network methods. Our results also demonstrate the importance of thoroughly testing for multiple sources of conflict in phylogenomic analyses, especially in the context of ancient, rapid radiations. We provide several recommendations for exploring conflicting signals in such situations.

evolutionary biology↗

bioRxiv2019

Separation of hemodynamic signals from GCaMP fluorescence measured with widefield imaging

Widefield calcium imaging is often used to measure brain dynamics in behaving mice. With a large field of view and a high sampling rate, widefield imaging can monitor activity from several distant cortical areas simultaneously, revealing cortical interactions. Interpretation of widefield images is complicated, however, by the absorption of light by hemoglobin, which can substantially affect the measured fluorescence. One approach to separating hemodynamics and calcium signals is to use multi-wavelength backscatter recordings to measure light absorption by hemoglobin. Following this approach, we develop a spatially-detailed regression-based method to estimate hemodynamics. The spatially-detailed model is based on a linear form of the Beer-Lambert relationship, but is fit at every pixel in the image and does not rely on the estimation of physical parameters. In awake mice of three transgenic lines, the Spatial Model offers improved separation of hemodynamics and changes in GCaMP fluorescence. The improvement is pronounced near blood vessels and, in contrast with other models based on regression or the Beer-Lambert law, can remove vascular artifacts along the sagittal midline. Compared to other separation approaches, the spatially-detailed model permits more accurate fluorescence-based determination of neuronal activity across the cortex.\n\nNEW & NOTEWORTHYThis manuscript addresses a well-known and strong source of contamination in widefield calcium imaging data: hemodynamics. To guide researchers towards the best method to separate calcium signals from hemodynamics, we compare the performance of several commonly used methods in three commonly-used Cre-driver lines, and we present a novel regression model that out-performs the other techniques we consider.

neuroscience↗

bioRxiv2019

Syndecan-1 facilitates breast cancer metastasis to the brain

PurposeAlthough survival rates for patients with localized breast cancer have increased, patients with metastatic breast cancer still have poor prognosis. Understanding key factors involved in promoting breast cancer metastasis is imperative for better treatments. In this study, we investigated the role of syndecan-1 (Sdc1) in breast cancer metastasis. MethodsTo assess the role of Sdc1 in breast cancer metastasis, we silenced Sdc1 expression in the triple-negative breast cancer human MDA-MB-231 cell line and overexpressed it in the mouse mammary carcinoma 4T1 cell line. Intracardiac injections were performed in an experimental mouse metastasis model using both cell lines. In vitro transwell blood-brain barrier (BBB) and brain section adhesion assays were utilized to specifically investigate how Sdc1 promotes brain metastasis. A cytokine array was performed to evaluate differences in the breast cancer cell secretome when Sdc1 was silenced. ResultsSilencing expression of Sdc1 in breast cancer cells significantly reduced metastasis to the brain. Conversely, overexpression of Sdc1 increased metastasis to the brain. We found that the reduction in brain metastases with Sdc1 knockdown was likely due to reduced breast cancer cell migration across the BBB and adhesion to the perivascular regions of the brain. However, there was no change in attachment to brain endothelial cells or astrocytes. Loss of Sdc1 also led to changes in breast cancer cell-secreted cytokines, which may influence the BBB. ConclusionsTaken together, our study demonstrates a role for Sdc1 in promoting breast cancer metastasis to the brain. These findings suggest that Sdc1 supports breast cancer cell migration across the BBB through regulation of cytokines, which may modulate the BBB. Further elucidating this mechanism will allow for the development of therapeutic strategies to combat brain metastasis.

cancer biology↗

bioRxiv2019

Reconstructing and Analysing The Genome of The Last Eukaryote Common Ancestor to Better Understand the Transition from FECA to LECA.

It is still a matter of debate whether the First Eukaryote Common Ancestor (FECA) arose from the merger of an archaeal host with an alphaproteobacterium, or was a proto-eukaryote with significant eukaryotic characteristics way before endosymbiosis occurred. The Last Eukaryote Common Ancestor (LECA) as its descendant is thought to be an entity that possessed functional and cellular complexity comparable to modern organisms. The precise nature and physiology of both of these organisms has been a long-standing, unanswered question in evolutionary and cell biology. Recently, a much broader diversity of eukaryotic genomes has become available and this means we can reconstruct early eukaryote evolution with a greater deal of precision. Here, we reconstruct a hypothetical genome for LECA from modern eukaryote genomes. The constituent genes were mapped onto 454 pathways from the KEGG database covering cellular, genetic, and metabolic processes across six model species to provide functional insights into its capabilities. We reconstruct a LECA that was a facultatively anaerobic, single-celled organism, similar to a modern Protist possessing complex predatory and sexual behaviour. We go on to examine how much of these capabilities arose along the FECA-to-LECA transition period. We see a at least 1,554 genes gained by FECA during this evolutionary period with extensive remodelling of pathways relating to lipid metabolism, cellular processes, genetic information processing, protein processing, and signalling. We extracted the BRITE classifications for the genes from the KEGG database, which arose during the transition from FECA-to-LECA and examine the types of genes that saw the most gains and what novel classifications were introduced. Two-thirds of our reconstructed LECA genome appears to be prokaryote in origin and the remaining third consists of genes with functional classifications that originate from prokaryote homologs in our LECA genome. Signal transduction and Post Translational Modification elements stand out as the primary novel classes of genes developed during this period. These results suggest that largely the eukaryote common ancestors achieved the defining characteristics of modern eukaryotes by primarily expanding on prokaryote biology and gene families.

evolutionary biology↗

bioRxiv2018

Ribosomal stress-induced senescence as a novel pro-senescence strategy for p16 positive basal-like breast cancer

Re-engaging the senescent programme represents an attractive yet underexplored strategy for cancer therapy, particularly for those tumour subtypes where targeted agents are limited or unavailable. Here, we identify a specific subset of ribosomal proteins as novel pro-senescence therapeutic targets for a highly aggressive subtype of breast cancer, p16 positive basal-like breast cancer. Mechanistically, ribosomal stress-induced senescence generates a stable cell cycle arrest, is dependent on endogenous p16 triggering a resensitisation to the p16/RB tumour suppressor axis, followed by establishment of a senescence-associated secretory phenotype, and is independent of DNA damage. Conversely, ribosomal protein knockdown in a p16 negative breast cancer model results in caspase-mediated apoptosis. Importantly, individual ribosomal protein loss is well tolerated by a panel of normal human cells. We demonstrate a reciprocal feedback loop between loss of RPS3A and RPS7 at both the transcriptional and post-transcriptional level during ribosomal stress-induced senescence. Further, our ribosomal hits are co-ordinately dysregulated in breast cancer, with elevated expression associated with a poor prognosis. Clinical relevance is demonstrated in tissue microarrays, and a RPS3AHIGHRPS7HIGH signature is associated with an earlier disease onset and synergises with p16 to further worsen patient outcome. We conclude that dysregulation of ribosomal proteins constitutes a cancer cell-specific mechanism of senescence evasion and that engaging ribosomal stress-induced senescence may be relevant for future pro-senescence therapies.

cancer biology↗

bioRxiv2018

Genetic data and cognitively-defined late-onset Alzheimer’s disease subgroups

Categorizing people with late-onset Alzheimers disease into biologically coherent subgroups is important for personalized medicine. We evaluated data from five studies (total n=4 050, of whom 2 431 had genome-wide single nucleotide polymorphism (SNP) data). We assigned people to cognitively-defined subgroups on the basis of relative performance in memory, executive functioning, visuospatial functioning, and language at the time of Alzheimers disease diagnosis. We compared genotype frequencies for each subgroup to those from cognitively normal elderly controls. We focused on APOE and on SNPs with p<10-5 and odds ratios more extreme than those previously reported for Alzheimers disease (<0.77 or >1.30). There was substantial variation across studies in the proportions of people in each subgroup. In each study, higher proportions of people with isolated substantial relative memory impairment had [≥]1 APOE e4 allele than any other subgroup (overall p= 1.5 x 10-27). Across subgroups, there were 33 novel suggestive loci across the genome with p<10-5 and an extreme OR compared to controls, of which none had statistical evidence of heterogeneity and 30 had ORs in the same direction across all datasets. These data support the biological coherence of cognitively-defined subgroups and nominate novel genetic loci.

genetics↗

bioRxiv2017

Improved Transcriptome Sampling Pinpoints 26 Paleopolyploidy Events In Caryophyllales, Including Two Paleo-Allopolyploidy Events

O_LIStudies of the macroevolutionary legacy of paleopolyploidy are limited by an incomplete sampling of these events across the tree of life. To better locate and understand these events, we need comprehensive taxonomic sampling as well as homology inference methods that accurately reconstruct the frequency and location of gene duplications.\nC_LIO_LIWe assembled a dataset of transcriptomes and genomes from 169 species in Caryophyllales, of which 43 were newly generated for this study, representing one of the densest sampled genomic-scale datasets yet available. We carried out phylogenomic analyses using a modified phylome strategy to reconstruct the species tree. We mapped phylogenetic distribution of paleopolyploidy events by both tree-based and distance-based methods, and explicitly tested scenarios for paleo-allopolyploidy.\nC_LIO_LIWe identified twenty-six paleopolyploidy events distributed throughout Caryophyllales, and using novel techniques inferred two to be paleo-allopolyploidy.\nC_LIO_LIThrough dense phylogenomic sampling, we show the propensity of paleo-polyploidy in the clade Caryophyllales. We also provide the first method for utilizing transcriptome data to detect paleo-allopolyploidy, which is important as it may have different macro-evolutionary implications compared to paleo-autopolyploidy.\nC_LI

evolutionary biology↗

bioRxiv2017

Disparity, Diversity, And Duplications In The Caryophyllales

O_LIThe role whole genome duplication (WGD) plays in the history of lineages is actively debated. WGDs have been associated with advantages including superior colonization, various adaptations, and increased effective population size. However, the lack of a comprehensive mapping of WGDs within a major plant clade has led to uncertainty regarding the potential association of WGDs and higher diversification rates.\nC_LIO_LIUsing seven chloroplast and nuclear ribosomal genes, we constructed a phylogeny of 5,036 species of Caryophyllales, representing nearly half of the extant species. We phylogenetically mapped putative WGDs as identified from analyses on transcriptomic and genomic data and analyzed these in conjunction with shifts in climatic niche and lineage diversification rate.\nC_LIO_LIThirteen putative WGDs and twenty-seven diversification shifts could be mapped onto the phylogeny. Of these, four WGDs were concurrent with diversification shifts, with other diversification shifts occurring at more recent nodes than WGDs. Five WGDs were associated with shifts to colder climatic niches.\nC_LIO_LIWhile we find that many diversification shifts occur after WGDs it is difficult to consider diversification and duplication to be tightly correlated. Our findings suggest that duplications may often occur along with shifts in either diversification rate, climatic niche, or rate of evolution.\nC_LI

evolutionary biology↗