Biology subjects

Brewer, G.

Publications and source records attributed to Brewer, G..

5 recordsLinked to original sources

bioRxiv2025

Classification of Urticaceae based on morphology and phylogenetic inference

The Urticaceae (ca. 2600 species) were first formally recognized by Jussieu in the 18th century and last comprehensively monographed by Weddell in the 19th century. Since Weddells work, family delimitation has been modified and many genera described in a fragmented manner. Over the past two decades, numerous molecular studies have supported the inclusion of Cecropiaceae within Urticaceae and identified paraphyly in several genera, notably Laportea, Urera, Boehmeria, Parietaria, Pellionia, and Pouzolzia. However, few studies have translated these molecular insights into a revised taxonomy. This study aimed to provide a robust, updated classification for Urticaceae by: a) increasing taxon and genomic locus sampling through the integration of newly generated sequence data with previously published datasets; and b) incorporating morphological data to support a revised delimitation of tribes and genera, and to establish a new linear sequence for the family. We also sought to identify remaining taxonomic challenges. Using Sanger and Angiosperms353 sequence data, we constructed a phylogenetic framework for 57 out of 59 currently accepted genera. We also assessed the phylogenetic informativeness of 57 morphological characters by mapping them onto the phylogeny. Our analyses support the delimitation of 61 monophyletic genera and an infrafamilial classification comprising seven tribes, two of which we describe as new: Myriocarpeae and Leukosykeae. We provide a revised linear sequence for the family. Our classification reinstates several names previously treated as synonyms (Fleurya, Leptocnide, Margarocarpus, Polychroa, Scepocarpus, Sceptrocnide), places several genera in synonymy (Hemistylus and Rousselia under Pouzolzia; Hesperocnide under Urtica; Gesnouinia and Soleirolia under Parietaria), and proposes the recognition of two new genera, Muimar gen. nov. and Pouzolziella gen. nov., to accommodate Boehmeria nivea and Pouzolzia australis, respectively. Mapping morphological characters onto the phylogeny indicates that while most states are homoplastic at the family level, their combination is valuable for recognizing genera. Geographic character mapping suggests a high degree of spatial conservatism at the genus rank. Our dated ultrametric tree suggests an origin for Urticaceae in Indomalaya during the mid-Cretaceous, followed by establishment in the Laurasian boreotropical flora and subsequent dispersal to the neotropics and Africa. Once classified within an evolutionary framework we believe that the Urticaceae represent a valuable study system in evolutionary biology for investigating transitions across biomes, the drivers of floral trait evolution, and intrinsic speciation mechanisms. New tribes: --Leukosykeae, Myriocarpeae New genera: --Muimar, Pouzolziella

evolutionary biology↗

bioRxiv2023

Enterovirus Evolution Reveals the Mechanism of an RNA-Targeted Antiviral and Determinants of Viral Replication

Selective pressures on positive-strand RNA viruses provide opportunities to establish target site specificity and mechanisms of action of antivirals. Here, Enterovirus-A71 revertant viruses with resistant mutations in the SLII IRES domain (SLIIresist) were selected at low doses of the antiviral DMA-135. The EV-A71 revertant viruses were resistant to DMA-135 at concentrations that robustly inhibit replication of wild-type virus. EV-A71 IRES structures harboring the suppressor mutations induced efficient expression of reporter Luciferase mRNA in the presence of non-cytotoxic doses of DMA-135 whereas DMA-135 dose-dependently inhibited Luciferase expression from the wild-type IRES element. NMR studies indicate that the resistant mutations change the structure of SLII at the bulge loop binding site of DMA-135 and at part of an extended surface recognized by host RNA-binding protein AUF1. Comparisons of biophysical analysis of complexes formed between AUF1, DMA-135, or either SLII or SLIIresist show that DMA-135 stabilizes a ternary complex with AUF1-SLII but not AUF1-SLIIresist. Further studies demonstrate that the hnRNP A1 protein retains binding affinity for SLIIresist, illustrating that DMA-135 inhibition and viral resistance do not perturb the SLII-hnRNP A1 arm of the regulatory axis. Taken together, this work demonstrates how viral evolution under selective pressures of small molecules can elucidate RNA binding site specificity, mechanisms of action, and provide additional insights into the viral pathways inhibited by the antiviral DMA-135.

molecular biology↗

bioRxiv2021

A Comprehensive Phylogenomic Platform for Exploring the Angiosperm Tree of Life

The tree of life is the fundamental biological roadmap for navigating the evolution and properties of life on Earth, and yet remains largely unknown. Even angiosperms (flowering plants) are fraught with data gaps, despite their critical role in sustaining terrestrial life. Today, high-throughput sequencing promises to significantly deepen our understanding of evolutionary relationships. Here, we describe a comprehensive phylogenomic platform for exploring the angiosperm tree of life, comprising a set of open tools and data based on the 353 nuclear genes targeted by the universal Angiosperms353 sequence capture probes. This paper (i) documents our methods, (ii) describes our first data release and (iii) presents a novel open data portal, the Kew Tree of Life Explorer (https://treeoflife.kew.org). We aim to generate novel target sequence capture data for all genera of flowering plants, exploiting natural history collections such as herbarium specimens, and augment it with mined public data. Our first data release, described here, is the most extensive nuclear phylogenomic dataset for angiosperms to date, comprising 3,099 samples validated by DNA barcode and phylogenetic tests, representing all 64 orders, 404 families (96%) and 2,333 genera (17%). Using the multi-species coalescent, we inferred a "first pass" angiosperm tree of life from the data, which totalled 824,878 sequences, 489,086,049 base pairs, and 532,260 alignment columns. The tree is strongly supported and highly congruent with existing taxonomy, while challenging numerous hypothesized relationships among orders and placing many genera for the first time. The validated dataset, species tree and all intermediates are openly accessible via the Kew Tree of Life Explorer. This major milestone towards a complete tree of life for all flowering plant species opens doors to a highly integrated future for angiosperm phylogenomics through the systematic sequencing of standardised nuclear markers. Our approach has the potential to serve as a much-needed bridge between the growing movement to sequence the genomes of all life on Earth and the vast phylogenomic potential of the worlds natural history collections.

evolutionary biology↗

bioRxiv2020

Amilorides inhibit SARS-CoV-2 replication in vitro by targeting RNA structures

The SARS-CoV-2 pandemic, and the likelihood of future coronavirus pandemics, has rendered our understanding of coronavirus biology more essential than ever. Small molecule chemical probes offer to both reveal novel aspects of virus replication and to serve as leads for antiviral therapeutic development. The RNA-biased amiloride scaffold was recently tuned to target a viral RNA structure critical for translation in enterovirus 71, ultimately uncovering a novel mechanism to modulate positive-sense RNA viral translation and replication. Analysis of CoV RNA genomes reveal many conserved RNA structures in the 5-UTR and proximal region critical for viral translation and replication, including several containing bulge-like secondary structures suitable for small molecule targeting. Following phylogenetic conservation analysis of this region, we screened an amiloride-based small molecule library against a less virulent human coronavirus, OC43, to identify lead ligands. Amilorides inhibited OC43 replication as seen in viral plaque assays. Select amilorides also potently inhibited replication competent SARS-CoV-2 as evident in the decreased levels of cell free virions in cell culture supernatants of treated cells. Reporter screens confirmed the importance of RNA structures in the 5-end of the viral genome for small molecule activity. Finally, NMR chemical shift perturbation studies of the first six stem loops of the 5-end revealed specific amiloride interactions with stem loops 4, 5a, and 6, all of which contain bulge like structures and were predicted to be strongly bound by the lead amilorides in retrospective docking studies. Taken together, the use of multiple orthogonal approaches allowed us to identify the first small molecules aimed at targeting RNA structures within the 5-UTR and proximal region of the CoV genome. These molecules will serve as chemical probes to further understand CoV RNA biology and can pave the way for the development of specific CoV RNA-targeted antivirals.

microbiology↗

bioRxiv2020

Small Molecule Targeting IRES Domain Inhibits Enterovirus 71 Replication via an Allosteric Mechanism that Stabilizes a Ternary Complex

We herein report an RNA-targeting antiviral small molecule that reduces replication of the human enterovirus 71 (EV71) via stabilization of an inhibitory small molecule-RNA-protein ternary complex. The EV71 virus poses serious threats to human health, particularly in regions of Southeast Asia, and no FDA approved drugs or vaccines are available. We first screened an RNA-biased small molecule library using a peptide-displacement assay to identify ligands for the stem loop II structure of the EV71 internal ribosomal entry site, which was previously shown to impact viral translation and replication. One ligand, DMA-135, decreased viral translation and replication in cell-based studies in a dose-dependent manner with no significant toxicity. Structural, biophysical, and biochemical characterization support an allosteric mechanism in which DMA-135 induces a conformational change in the RNA structure that stabilizes a ternary complex with the AUF1 protein that then represses translation. This mechanism was further supported by pull-down experiments in cell culture. These detailed studies establish enterovirus RNA structures as promising drug targets while revealing an approach and mechanism of action that should be broadly applicable to functional RNA targeting.

biochemistry↗