Biology subjects

Dewar, K.

Publications and source records attributed to Dewar, K..

4 recordsLinked to original sources

bioRxiv2022

Replication-associated inversions are the dominant form of bacterial chromosome structural variation

Structural arrangement of a bacterial chromosome varies widely between closely related species and can result in significant phenotypic outcomes. The appearance of large-scale chromosomal inversions that are symmetric relative to the dnaA gene (usually linked to oriC, the origin of replication) has been previously observed; however, the overall prevalence of replication-associated structural rearrangements (RASRs) in bacteria and their causal mechanisms are currently unknown. The decreased cost of full-length genome sequencing has led to a rapidly growing collection of complete genomes spanning multiple different clades, therefore allowing an opportunity to examine chromosomal inversions in the context of species spanning diverse phylogenetic classifications. Here we systematically identify the locations of large, chromosomal inversions in species with multiple complete sequenced genomes using the Refseq and Genbank NCBI databases to investigate potential mediating biological mechanisms. Out of the 239 species available with 10 or more complete genomes, 206 contained sequences with at least one large ([≥]50Kb) inversion in their set of within-species sequence comparisons. We observed 73.4% of the 127,161 large inversions were centered at a point within 10% proportionate distance to the annotated dnaA gene, which is often nearby the origin of replication. Inversions offset from the annotated dnaA sequence were generally confirmed to be centered on the actual origin of replication. Equidistant breakpoints from the replication origin and prevalence of flanking repeats provide evidence that the breaks that are formed during the replication process are then repaired to opposing positions. We also found a strong relationship between the later stages of replication and the range in variation of distance from symmetry, suggesting that replication fork arrest may be a mechanistic cause for the asymmetry in some inversions.

genomics↗

bioRxiv2019

Identification and characterization of OmpT-like proteases in uropathogenic Escherichia coli clinical isolates

Bacterial colonization of the urogenital tract is limited by innate defenses, including the production of antimicrobial peptides (AMPs). Uropathogenic Escherichia coli (UPEC) resist AMP-killing to cause a range of urinary tract infections (UTIs) including asymptomatic bacteriuria, cystitis, pyelonephritis, and sepsis. UPEC strains have high genomic diversity and encode numerous virulence factors that differentiate them from non-UTI causing strains, including ompT. As OmpT homologues cleave and inactivate AMPs, we hypothesized that high OmpT protease activity-levels contribute to UPEC colonization during symptomatic UTIs. Therefore, we measured OmpT activity in 58 UPEC clinical isolates. While heterogeneous OmpT activities were observed, OmpT activity was significantly greater in UPEC strains isolated from patients with symptomatic infections. Unexpectedly, UPEC strains exhibiting the greatest protease activities harboured an additional ompT-like gene called arlC (ompTp). The presence of two OmpT-like proteases in some UPEC isolates led us to compare the substrate specificities of OmpT-like proteases found in E. coli. While all three cleaved AMPs, cleavage efficiency varied on the basis of AMP size and secondary structure. Our findings suggest the presence ArlC and OmpT in the same UPEC isolate may confer a fitness advantage by expanding the range of target substrates.

microbiology↗

bioRxiv2018

De novo genome assembly of the olive fruit fly (Bactrocera oleae) developed through a combination of linked-reads and long-read technologies

Long-read sequencing has greatly contributed to the generation of high quality assemblies, albeit at a high cost. It is also not always clear how to combine sequencing platforms. We sequenced the genome of the olive fruit fly (Bactrocera oleae), the most important pest in the olive fruits agribusiness industry, using Illumina short-reads, mate-pairs, 10x Genomics linked-reads, Pacific Biosciences (PacBio), and Oxford Nanopore Technologies (ONT). The 10x linked-reads assembly gave the most contiguous assembly with an N50 of 2.16 Mb. Scaffolding the linked-reads assembly using long-reads from ONT gave a more contiguous assembly with scaffold N50 of 4.59 Mb. We also present the most extensive transcriptome datasets of the olive fly derived from different tissues and stages of development. Finally, we used the Chromosome Quotient method to identify Y-chromosome scaffolds and show that the long-reads based assembly generates very highly contiguous Y-chromosome assembly.\n\nJR is a member of the MinION Access Program (MAP) and has received free-of-charge flow cells and sequencing kits from Oxford Nanopore Technologies for other projects. JR has had no other financial support from ONT.\n\nAB has received re-imbursement for travel costs associated with attending Nanopore Community meeting 2018, a meeting organized my Oxford Nanopore Technologies.

genomics↗

bioRxiv2016

Genetic variation and gene expression across multiple tissues and developmental stages in a non-human primate

By analyzing multi-tissue gene expression and genome-wide genetic variation data in samples from a vervet monkey pedigree, we generated a transcriptome resource and produced the first catalogue of expression quantitative trait loci (eQTLs) in a non-human primate model. This catalogue contains more genome-wide significant eQTLs, per sample, than comparable human resources, and reveals sex and age-related expression patterns. Findings include a master regulatory locus that likely plays a role in immune function, and a locus regulating hippocampal long non-coding RNAs (lncRNAs), whose expression correlates with hippocampal volume. This resource will facilitate genetic investigation of quantitative traits, including brain and behavioral phenotypes relevant to neuropsychiatric disorders.

genetics↗