Biology subjects

Grant, C.

Publications and source records attributed to Grant, C..

4 recordsLinked to original sources

bioRxiv2026

Optimizing genome assembly, chromosome synteny, and genetic variant discovery from Oxford Nanopore sequences of Dermacentor reticulatus ticks

Generating high-quality genome assemblies for small animals with large genomes is complex due to their small body size, DNA contamination, and repetitive elements. Ticks exemplify these complexities, while also being a global health threat to humans, domestic animals, and wildlife. Advances in long-read sequencing platforms now make it feasible to obtain large amounts of raw sequence data from individual specimens, but challenges remain. Key genome workflow challenges include error correction, assembly, transposable element annotation, and chromosome assignment and synteny. Here we examine three individual Dermacentor reticulatus ticks using deep Oxford Nanopore sequencing. Comparing and contrasting bioinformatic tools for raw read and assembly manipulation allows us to identify the parameters that provide a high-quality haploid genome assembly among 38 assemblies. We find Dorado error corrected raw read data from approximately two flow cells are needed, but limiting assembly coverage to 40x produces the highest quality assemblies. Then we examined the effects of optimal workflow parameters on downstream analyses of gene synteny and manual transposable element annotation of the three tick assemblies in comparison to an independent assembly of a fourth D. reticulatus individual from a different country. Gene synteny analysis allows chromosome assignment of scaffolds and transposable element identification was improved markedly with manual curation. Finally, we compared the genetic variation of D. reticulatus across two populations and found similar genetic diversity. Our study provides a clear workflow to obtain high-quality assemblies from Oxford Nanopore sequences and genetic characterization of a species with a large, complex, and repetitive genome.

genomics↗

bioRxiv2025

A network of coiled-coil and actin-like proteins controls the cellular organization of magnetosome organelles in deep-branching magnetotactic bacteria

Magnetotactic Bacteria (MTB) are a diverse group of microorganisms that use magnetosomes, organelles composed of magnetite or greigite, to navigate along geomagnetic fields. While MTB span several phyla and exhibit diverse phenotypes, magnetosome formation has been mechanistically studied in only two species of Alphaproteobacteria. Here, we use Desulfovibrio magneticus RS-1 to uncover the mechanisms behind tooth-shaped magnetosome assembly in deep-branching MTB. Our findings show that magnetic particles in RS-1 initially form randomly within the cell before localizing to the positive cell curvature. Genetic and proteomic analyses indicate that early biomineralization involves membrane-associated proteins found in all MTB, while later stages depend on coiled-coil (Mad20, 23, 25, and 26) and actin-like (MamK and Mad28) proteins, most of which are unique to deep-branching MTB. These findings suggest that while biomineralization originates from a common ancestor, magnetosome chain organization has distinct evolutionarily origins among different MTB lineages.

microbiology↗

bioRxiv2024

A role for the putative error-prone polymerase REV1 in DNA damage and antifungal drug resistance in Candida albicans

Antimicrobial-induced DNA damage, and subsequent repair via upregulation of DNA repair factors, including error-prone translesion polymerases, can lead to the increased accumulation of mutations in the microbial genome, and ultimately increased risk of acquired mutations associated with antimicrobial resistance. While this phenotype is well described in bacterial species, it is less thoroughly investigated amongst microbial fungi. Here, we monitor DNA damage induced by antifungal agents in the fungal pathogen Candida albicans, and find that commonly used antifungal drugs are able to induce DNA damage, leading to the upregulation of transcripts encoding predicted error-prone polymerases and related factors. We focus on REV1, encoding a putative error-prone polymerase, and find that while deleting this gene in C. albicans leads to increased sensitivity to DNA damage, it also unexpectedly renders cells more likely to incur mutations and evolve resistance to antifungal agents. We further find that deletion of REV1 leads to a significant depletion in the uncharacterized protein Shm1, which itself plays a role in fungal mutagenesis. Together, this work lends new insight into previously uncharacterized factors with important roles in the DNA damage response, mutagenesis, and the evolution of antifungal drug resistance.

microbiology↗

bioRxiv2017

MoMo: Discovery of post-translational modification motifs

MotivationPost-translational modifications (PTMs) of proteins are associated with many significant biological functions and can be identified in high throughput using tandem mass spectrometry. Many PTMs are associated with short sequence patterns called \"motifs\" that help localize the modifying enzyme. Accordingly, many algorithms have been designed to identify these motifs from mass spectrometry data.\n\nResultsMoMo is a software tool for identifying motifs among sets of PTMs. The program re-implements two previously described algorithms, Motif-X and MoDL, packaging them in a web-accessible user interface. In addition to reading sequence files in FASTA format, MoMo is capable of directly parsing output files produced by commonly used mass spectrometry search engines. The resulting motifs are presented to the user in an HTML summary with motif logos and linked text files in MEME motif format.\n\nAvailabilitySource code and web server available at http://meme-suite.org\n\nContacttimothybailey@unr.edu and william-noble@uw.edu\n\nSupplementary informationSupplementary figures are available at Bioinformatics online.

bioinformatics↗