Biology subjects

Ramsden, D.

Publications and source records attributed to Ramsden, D..

4 recordsLinked to original sources

bioRxiv2022

Retrotransposons hijack alt-EJ DNA repair process for mobilization and eccDNA biogenesis

Parasitic retrotransposons populate in the genome to rewrite the hosts genetic code. How retrotransposons use the host factors to achieve their propagation remains largely unclear. Here we report retrotransposons hijack the alternative end-joining (alt-EJ) DNA repair process to accomplish mobilization cycle. We applied Nanopore sequencing to examine the fates of replicated retrotransposon DNA, and found that only 10% of them achieve integration, while 90% exist as extrachromosomal circular DNA (eccDNA). Using eccDNA production as a readout, further genetic screens identified factors from alt-EJ as essential for retrotransposon replication. alt-EJ drives the 2nd-strand synthesis of the retrotransposon DNA via a circularization process, thus is necessitated for eccDNA production and integrations. Our study reveals a conserved function of alt-EJ in promoting selfish element propagation, which potentially causes disease or drives evolution.

cell biology↗

bioRxiv2022

NeuVue: A Framework and Workflows for High-Throughput Electron Microscopy Connectomics Proofreading

Connectomic reconstruction from large image volumes produces segmentation and synaptic-assignment errors that must be resolved to support downstream analyses. As datasets have grown larger and teams more distributed, proofreading has become a critical operational bottleneck. Workflows for proofreading and error correction have not scaled commensurately with connectomic data production and may not accommodate heterogeneous proofreader expertise and machine-generated candidate edits. New tools are therefore needed to organize, prioritize, and coordinate proofreading at volume scale. Here we present NeuVue, a task-management and prioritization framework that operationalizes proofreading through atomic, auditable tasks for individual and team review, multistage routing across proofreader cohorts, performance and volume-state tracking, and integration with community annotation, visualization, and analysis services. We report the use of NeuVue across two volumetric datasets, supporting scalable proofreading by over forty proofreaders and producing over fifty thousand edits. NeuVue provides a reproducible human-in-the-loop framework for generating, validating, and maintaining large connectomic datasets.

neuroscience↗

bioRxiv2021

Unexpected post-glacial colonisation route explains the white colour of barn owls (Tyto alba) from the British Isles

The climate fluctuations of the Quaternary shaped the movement of species in and out of glacial refugia. In Europe, the majority of species followed one of the described traditional postglacial recolonization routes from the southern peninsulas towards the north. Like most organisms, barn owls are assumed to have colonized the British Isles by crossing over Doggerland, a land bridge that connected Britain to northern Europe. However, while they are dark rufous in northern Europe, barn owls in the British Isles are conspicuously white, a contrast that could suggest selective forces are at play on the islands. However, analysis of known candidate genes involved in colouration found no signature of selection. Instead, using whole genome sequences and species distribution modelling, we found that owls colonised the British Isles soon after the last glaciation, directly from a white coloured refugium in the Iberian Peninsula, before colonising northern Europe. They would have followed a yet unknown post-glacial colonization route to the Isles over a westwards path of suitable habitat in now submerged land in the Bay of Biscay, thus not crossing Doggerland. As such, they inherited the white colour of their Iberian founders and maintained it through low gene flow with the mainland that prevents the import of rufous alleles. Thus, we contend that neutral processes likely explain this contrasting white colour compared to continental owls. With the barn owl being a top predator, we expect future research will show this unanticipated route was used by other species from its paleo community.

evolutionary biology↗

bioRxiv2019

The Drosophila melanogaster ortholog of RFWD3 functions independently of RAD51 during DNA repair

Repair of damaged DNA is required for the viability of all organisms. Studies in Drosophila melanogaster, driven by the power of genetic screens, pioneered the discovery and characterization of many genes and pathways involved in DNA repair in animals. However, fewer than half of the alleles identified in these screens have been mapped to a specific gene, leaving a potential for new discoveries in this field. Here we show that the previously uncharacterized mutagen sensitive gene mus302 codes for the Drosophila melanogaster ortholog of the E3 ubiquitin ligase RING finger and WD domain protein 3 (RFWD3). In human cells, RFWD3 promotes ubiquitylation of RPA and RAD51 to facilitate repair of collapsed replication forks and double strand breaks through homologous recombination. Despite the high similarity in sequence to the human ortholog, our evidence fails to support a role for Mus302 in the repair of these types of damage. Last, we observe that the N-terminal third of RFWD3 is only present in mammals and absent in the rest of vertebrates and invertebrates. We propose that the additional N-terminal portion accounts for the acquisition of a new biological function in mammals that explains the functional differences between the human and the fly orthologs, and that Drosophila Mus302 may retain the ancestral function of the protein.

genetics↗