Biology subjects

Jones, R. E.

Publications and source records attributed to Jones, R. E..

11 recordsLinked to original sources

bioRxiv2026

Integrative morphology and phylogenetics of Arcellidae (Amoebozoa:Arcellinida), with redescription of Arcella leidyana and Arcella artocrea and description of Galeripora purdoni sp. nov.

Arcellidae is a family of testate amoebae within Arcellinida (Amoebozoa), comprising three recognized genera: Arcella, Galeripora, and Antarcella. Although species in the family have been studied for nearly two centuries, many historically described taxa and major morphological groups remain unsampled at the molecular level. Here, we provide a comprehensive review of Arcellidae and generate new cytochrome c oxidase subunit I (COI) sequences for arcellid species from Canadian peatlands, focusing on tall-shelled Arcella historically classified in section Altae sensu Deflandre. COI phylogenetic analyses recover a strongly supported monophyletic clade corresponding to North American representatives of Altae, providing the first molecular corroboration of this morphologically defined group. Within this clade, we redescribe Arcella leidyana based on modern material from Eeyou Istchee (Quebec). We further describe Galeripora purdoni sp. nov. from a calcareous fen in eastern Ontario, representing a novel terrestrial lineage within the genus, and redescribe Galeripora artocrea, which we transfer to Arcella based on congruent molecular and morphological evidence. Phylogenomic analyses of Arcellidae isolates from the Protist 10,000 Genomes Project reveal an additional deep lineage basal to Arcella and Galeripora. Together, these results highlight hidden diversity and demonstrate the importance of integrative approaches for resolving arcellid systematics and refining its classification.

evolutionary biology↗

bioRxiv2025

Pyrumthecina Infraorder Nov.: Revisiting the morphological diversity and identifying the phylogenetic home of Argynnia within Arcellinida (Tubulinea:Amoebozoa)

Arcellinida is a diverse lineage of testate amoebae within Amoebozoa, whose evolutionary history has been clarified through phylogenomics. These efforts have led to a stable classification of the group into suborders and infraorders. However, several taxa, such as the genus Argynnia, remain unplaced due to ambiguous morphology and unresolved positions in single-gene phylogenies. In this study, we explore the diversity of Argynnia by presenting new records of species sampled across Brazil. To address its longstanding taxonomic uncertainty, we performed a phylogenomic analysis incorporating transcriptomic data from the Protist 10,000 Genomes isolate P10K-MW-000941 (P10K941). Through single-gene phylogenies, this isolate was shown to be closely related to Argynnia, which previously lacked genomic-level data. Here, we further confirm this relationship and present a 227-gene phylogenomic reconstruction that identifies the placement of P10K941 within Arcellinida, thereby resolving the phylogenetic placement of Argynnia. We obtained a curated, contaminant-free phylogenomic dataset for Arcellinida, including the P10K941, through the PhyloFisher workflow. Our analysis recovers P10K941 as a well-supported long-branch, sister to the infraorder Longithecina. Given this phylogenomic placement, along with Argynnias characteristic morphology and the consistent results of single-marker analyses placing it outside existing infraorders, we propose the Pyrumthecina infraorder novum and the family Argynniidae family novum to accommodate the P10K941 isolate and all Argynnia species. These findings resolve the phylogenetic position of Argynnia and allow for interpreting shell evolution and deep diversification patterns within Arcellinida. The recognition of Pyrumthecina also highlights the likely existence of deeply branching lineages among arcellinid taxa currently classified as incertae sedis.

evolutionary biology↗

bioRxiv2025

Phylogenetic placement and contamination screening of Amoebozoa genomic data from the Protist 10,000 Genomes (P10K) Database

BackgroundGenomic data are essential for uncovering the evolutionary history, ecological roles, and diversity of life. Yet, diverse microbial eukaryotes, predominantly unicellular and traditionally referred to as protists, remain critically underrepresented in genomic repositories, limiting our ability to address fundamental questions in eukaryotic evolution. The Protist 10,000 Genomes (P10K) initiative seeks to fill this gap by generating and compiling genomic and transcriptomic data for a wide range of microbial eukaryotes. However, large-scale sequencing efforts face persistent challenges, including contamination and imprecise taxonomic identification, particularly for poorly studied taxa that require specialized taxonomic expertise. To ensure the reliability of these resources, robust and scalable approaches for taxonomic identification and contamination screening are essential. ResultsWe developed CSI-SSU (https://github.com/AlexTiceLab/CSI-SSU), a command-line tool for Contaminant Sequence Investigation (CSI) that uses small subunit ribosomal RNA (SSU) sequences, chimeric sequence detection, and phylogenetic placement to rapidly identify, retrieve, and classify SSU sequences from eukaryotic genomic-level assemblies. CSI-SSU incorporates a curated SSU reference dataset representing the major known eukaryotic supergroups, with sequences and taxonomic nomenclature derived from the Protist Ribosomal Reference (PR2) database. In addition to detecting contaminant sequences, CSI-SSU enables approximate taxonomic assignment of the target lineage in each assembly, with resolution constrained by the current diversity represented in PR2. To further assess potential bacterial contamination, CSI-SSU employs bacterial BUSCO searches as a proxy. We demonstrate CSI-SSU utility and performance by screening 2,960 genomic-level assemblies spanning a broad diversity of eukaryotes from P10K. CSI-SSU efficiently detected non-target eukaryotic SSU sequences, revealing cross-group contamination. Classifications also corroborated or refined the original taxonomic assignments, with resolution depending on PR2 representation. Bacterial BUSCO searches indicated bacterial contamination. Independent SSU and COI phylogenies of Amoebozoa supported CSI-SSU classifications, highlighting its accuracy and sensitivity. ConclusionCSI-SSU provides a scalable and reproducible framework for phylogenetically informed contamination screening and taxonomic validation of genomic and transcriptomic data. Coupling phylogenetic placement with contamination detection enabled us to distinguish high-quality P10K datasets from those requiring decontamination or additional sequencing before downstream use. These findings serve as a reference for future analyses and guide further sequencing efforts to expand the taxonomic diversity of microbial eukaryotes at the genomic level. Addressing imprecise taxonomic assignments, contamination, and reproducibility in genomic-level datasets will enhance the value of these resources and facilitate studies illuminating the evolution and diversification of eukaryotic life.

genomics↗

bioRxiv2025

Uracil-DNA glycosylase deficiency is associated with repressed tumor cell-intrinsic inflammatory signaling and altered sensitivity to exogenous interferons

2-deoxyuridine (dU) is a common DNA lesion resulting from cytosine deamination and from dUMP incorporation by DNA polymerases, both of which are prevalent in cancer. The primary mechanism that repairs dU lesions in genomic DNA is base excision repair initiated by Uracil-DNA Glycosylase 1 (UNG1). We generated Ung knockout mouse B16 melanoma cells to investigate the consequences of UNG deficiency in a well-characterized, immunoproficient, syngeneic mouse cancer model. We show that UNG-deficient ({Delta}UNG) B16 tumors have altered growth kinetics in vivo and that their delayed growth is T-cell dependent. Immune profiling revealed reduced CD8+ T cell infiltration but augmented CD4+ Th1 responses in {Delta}UNG tumors. In vitro, {Delta}UNG tumor cells exhibit strongly suppressed cell-intrinsic type-I interferon, type-II interferon, and inflammatory signaling gene expression signatures as well as altered cytokine and chemokine secretion. In vivo, {Delta}UNG tumors exhibit a modified inflammatory cytokine and chemokine milieu. Furthermore, {Delta}UNG tumor cells have altered sensitivity to exogenous interferons in vitro, with increased sensitivity to IFN-{gamma} but decreased sensitivity to IFN-/{beta}. Collectively, our data show that tumor cell-specific UNG deficiency results in an altered tumor microenvironment in vivo and provide proof-of-concept data for the use of UNG inhibitors to modulate inflammatory pathways in tumors.

cancer biology↗

bioRxiv2024

Deoxyuridine-rich cytoplasmic DNA antagonizes STING-dependent innate immune responses and sensitizes resistant tumors to anti-PD-L1 therapy

DNA damage and cytoplasmic DNA induce type-1 interferon (IFN-1) and potentiate responses to immune checkpoint inhibitors. Our prior work found that inhibitors of the DNA damage response kinase ATR (ATRi) induce IFN-1 and deoxyuridine (dU) incorporation by DNA polymerases, akin to antimetabolites. Whether and how dU incorporation is required for ATRi-induced IFN-1 signaling is not known. Here, we show that ATRi-dependent IFN-1 responses require uracil DNA glycosylase (UNG)-initiated base excision repair and STING. Quantitative analyses of nine distinct nucleosides reveals that ATRi induce dU incorporation more rapidly in UNG wild-type than knockout cells, and that induction of IFN-1 is associated with futile cycles of repair. While ATRi induce similar numbers of micronuclei in UNG wild-type and knockout cells, dU containing micronuclei and cytoplasmic DNA are increased in knockout cells. Surprisingly, DNA fragments containing dU block STING-dependent induction of IFN-1, MHC-1, and PD-L1. Furthermore, UNG knockout sensitizes cells to IFN-{gamma} in vitro, and potentiates responses to anti-PD-L1 in resistant tumors in vivo. These data demonstrate an unexpected and specific role for dU-rich DNA in suppressing STING-dependent IFN-1 responses, and show that UNG-deficient tumors have a heightened response to immune checkpoint inhibitors. STATEMENT OF SIGNIFICANCEAntimetabolites disrupt nucleotide pools and increase dU incorporation by DNA polymerases. We show that unrepaired dU potentiates responses to checkpoint inhibitors in mouse models of cancer. Patients with low tumor UNG may respond to antimetabolites combined with checkpoint inhibitors, and patients with high tumor UNG may respond to UNG inhibitors combined with checkpoint inhibitors.

cancer biology↗

bioRxiv2023

A PhyloFisher utility for nucleotide-based phylogenomic matrix construction; nucl_matrix_constructor.py

Phylogenies built from multiple genes have become a common component of evolutionary biology studies. Molecular phylogenomic matrices used to build multi-gene phylogenies can be built from either nucleotide or protein matrices. Nucleotide-based analyses are often more appropriate for addressing phylogenetic questions in evolutionarily shallow timescales (i.e., less than 100 million years) while protein-based analyses are often more appropriate for addressing deep phylogenetic questions. PhyloFisher is a phylogenomic software package written in Python3. The manually curated PhyloFisher database contains 240 protein-coding genes from 304 eukaryotic taxa. Here we present nucl_matrix_constructor.py, an expansion of the PhyloFisher starting database, and an update to PhyloFisher that maintains DNA sequences. This combination will allow users the ability to easily build nucleotide phylogenomic matrices while retaining the benefits of protein-based pre-processing used to identify contaminants and paralogy.

bioinformatics↗

bioRxiv2023

Time perception reflects individual differences in motor and non-motor symptoms of Parkinson's disease

Dopaminergic signaling in the striatum has been shown to play a critical role in the perception of time. Decreasing striatal dopamine efficacy is at the core of Parkinsons disease (PD) motor symptoms and changes in dopaminergic action have been associated with many comorbid non-motor symptoms in PD. We hypothesize that patients with PD perceive time differently and in accordance with their specific comorbid non-motor symptoms and clinical state. We recruited patients with PD and compared individual differences in patients clinical features with their ability to judge millisecond to second intervals of time (500ms-1100ms) while on or off their prescribed dopaminergic medications. We show that individual differences in comorbid non-motor symptoms, PD duration, and prescribed dopaminergic pharmacotherapeutics account for individual differences in time perception performance. We report that comorbid impulse control disorder is associated with temporal overestimation; depression is associated with decreased temporal accuracy; and PD disease duration and prescribed levodopa monotherapy are associated with reduced temporal precision and accuracy. Observed differences in time perception are consistent with hypothesized dopaminergic mechanisms thought to underlie the respective motor and non-motor symptoms in PD, but also raise questions about specific dopaminergic mechanisms. In future work, time perception tasks like the one used here, may provide translational or reverse translational utility in investigations aimed at disentangling neural and cognitive systems underlying PD symptom etiology. One Sentence SummaryQuantitative characterization of time perception behavior reflects individual differences in Parkinsons disease motor and non-motor symptom clinical presentation that are consistent with hypothesized neural and cognitive mechanisms.

neuroscience↗

bioRxiv2021

Regulation of Blos1 by IRE1 prevents the accumulation of Huntingtin protein aggregates

Huntingtons disease is characterized by accumulation of the aggregation-prone mutant Huntingtin (mHTT) protein. Here, we show that expression of mHTT in mouse cultured cells activates IRE1, the transmembrane sensor of stress in the endoplasmic reticulum, leading to degradation of the Blos1 mRNA and repositioning of lysosomes and late endosomes toward the microtubule organizing center. Overriding Blos1 degradation results in excessive accumulation of mHTT aggregates in both cultured cells and primary neurons. Although mHTT is degraded by macroautophagy when highly expressed, we show that prior to the formation of large aggregates, mHTT is degraded via an ESCRT-dependent, macroautophagy-independent pathway consistent with endosomal microautophagy. This pathway is enhanced by Blos1 degradation and appears to protect cells from a toxic, less aggregated form of mHTT. Condensed titleBlos1 regulation protects from Huntingtin aggregation Short summaryHere the authors demonstrate that the regulation of Blos1 by the unfolded protein response prevents the excessive accumulation of Huntingtin, the protein that underlies Huntingtons disease. This pathway involves the macroautophagy-independent degradation of Huntingtin prior to its forming large aggregates.

cell biology↗

bioRxiv2021

Integrated spatial multi-omics reveals fibroblast fate during tissue repair

In the skin, tissue injury results in fibrosis in the form of scars composed of dense extracellular matrix deposited by fibroblasts. The therapeutic goal of regenerative wound healing has remained elusive in part because principles of fibroblast programming and adaptive response to injury remain incompletely understood. Here, we present a multimodal -omics platform for the comprehensive study of cell populations in complex tissue, which has allowed us to characterize the cells involved in wound healing across both time and space. We employ a stented wound model that recapitulates human tissue repair kinetics and multiple Rainbow transgenic lines to precisely track fibroblast fate during the physiologic response to injury. Through integrated analysis of single cell chromatin landscapes and gene expression states, coupled with spatial transcriptomic profiling, we are able to impute fibroblast epigenomes with temporospatial resolution. This has allowed us to define the mechanisms controlling cell fate during migration, proliferation, and differentiation following tissue injury and thereby reexamine the canonical phases of wound healing. These findings have broad implications for the study of tissue repair in complex organ systems.

bioinformatics↗

bioRxiv2021

Modest changes in Spi1 dosage reveal the potential for altered microglial function as seen in Alzheimers disease

Genetic association studies have identified multiple variants at the SPI1 locus that modify risk and age of onset for Alzheimers Disease (AD). Reports linking risk variants to gene expression suggest that variants denoting higher SPI1 expression are likely to have an earlier AD onset, and several other AD risk genes contain PU.1 binding sites in the promoter region. Overall, this suggests altered levels of SPi1 may alter microglial phenotype potentially impacting AD. This study determined how the mouse microglial transcriptome was altered following modest changes to Spi1 expression in primary microglia. RNA-sequencing was performed on microglia with reduced or increased Spi1/PU.1 expression to provide an unbiased approach to determine transcriptomic changes affected by Spi1. In summary, a reduction in microglial Spi1 resulted in the dysregulation of transcripts encoding proteins involved in DNA replication pathways while an increased Spi1 results in an upregulation of genes associated with immune response pathways. Additionally, a subset of 194 Spi1 dose-sensitive genes was identified and pathway analysis suggests that several innate immune and interferon response pathways are impacted by the concentration of Spi1. Together these results suggest Spi1 levels can alter the microglial transcriptome and suggests interferon pathways may be altered in individuals with AD related Spi1 risk SNPs.

neuroscience↗

bioRxiv2020

The integrin-mediated adhesome complex, essential to multicellularity, is present in the most recent common ancestor of animals, fungi, and amoebae

Integrins are transmembrane receptor proteins that activate signal transduction pathways upon extracellular matrix binding. The Integrin Mediated Adhesion Complex (IMAC), mediates various cell physiological process. The IMAC was thought to be an animal specific machinery until over the last decade these complexes were discovered in Obazoa, the group containing animals, fungi, and several microbial eukaryote lineages. Amoebozoa is the eukaryotic supergroup sister to Obazoa. Even though Amoebozoa represents the closest outgroup to Obazoa, little genomic-level data and attention to gene inventories has been given to the supergroup. To examine the evolutionary history of the IMAC, we examine gene inventories of deeply sampled set of 100+ Amoebozoa taxa, including new data from several taxa. From these robust data sampled from the entire breadth of known amoebozoan clades, we show the presence of an ancestral complex of integrin adhesion proteins that predate the evolution of the Amoebozoa. Our results highlight that many of these proteins appear to have evolved earlier in eukaryote evolution than previously thought. Co-option of an ancient protein complex was key to the emergence of animal type multicellularity. The role of the IMAC in a unicellular context is unknown but must also play a critical role for at least some unicellular organisms.

evolutionary biology↗