Biology subjects

Duffy, D. J.

Publications and source records attributed to Duffy, D. J..

5 recordsLinked to original sources

bioRxiv2026

Genomic indicators of risk and resilience in global leatherback turtle populations

Understanding the drivers of genomic health and their consequences for population viability is often overlooked but potentially important to effective conservation amidst the biodiversity crisis of the Anthropocene. Leatherback turtle (Dermochelys coriacea) populations have declined globally due to anthropogenic factors, with some populations losing over 90% of their abundance over the past 30-50 years. While conservation efforts have been successful in stabilizing some populations, others continue to decline, and the reasons for these differential trajectories remain unclear. To assess how recent demographic factors, such as population size and decline, influence population genomic health, we combined population monitoring information with medium depth whole-genome and reduced representation resequencing data from globally representative populations. We found that small-stable populations have lower genomic diversity and higher inbreeding than large declining populations, reflecting prolonged small population sizes and limited gene flow. Yet, small-stable populations also show evidence of deleterious allele purging, suggesting genetic resilience. This, combined with lack of detectable genomic erosion over the study period, provides hope for potential recovery of healthy leatherback populations provided that anthropogenic threats are effectively mitigated. However, potential time lags and possible recent increases in inbreeding among close relatives in recently declined populations warrant continued monitoring and assessment. Genomic and abundance-based metrics were less aligned following rapid population declines, emphasizing the different timescales of the evolutionary and demographic processes they reflect, respectively, and the strength in their complementary, integrative use for extinction risk assessments. This also supports that it is not too late to turn the tide for recently declined leatherback populations and that continued investment in conservation efforts and threat reductions are warranted. Collectively, our results highlight how recent and historical demography shapes current genomic health and recovery potential in leatherback turtles, aids understanding of current risks and informs future conservation and management strategies.

ecology↗

bioRxiv2024

Long-read nanopore shotgun eDNA sequencing for river biodiversity, pollution and environmental health monitoring

As global temperatures rise, species populations and biodiversity decline, and infectious diseases emerge all at unprecedented rates, it is more vital than ever to accurately understand the current state of natural habitats. While traditional methods including direct sampling and observation have their merits, newer technologies offer additional sampling capabilities. Here, we assess the feasibility of a single assay: shotgun long-read sequencing, to monitor species eDNA from across the tree of life, from viruses to complex multicellular organisms, across a river system (mountain tributary to sea). We conducted eDNA sampling and shotgun long-read sampling from water taken from the Avoca River watercourse, Co. Wicklow, Ireland, from a mountain tributary through to the sea, and comparative nearby beach sand sampling. We report that shotgun long-read sequencing and metagenomic analysis have utility for the detection and quantification of organismal DNA present in eDNA samples, from across the tree of life, from microbes (including DNA viruses) to mammals. With this single assay we were able to simultaneously quantify differences in eDNA abundance for a broad range of biodiversity and pathogens across sites and sample types. This included human, wildlife, plant and microbial pathogens and parasites with health, agricultural and economic importance. Additionally, the generated eDNA genomic data enabled population genetic applications even from natural complex community settings, as demonstrated here for blue mussels (Mytilus edulis). The results demonstrate that Oxford Nanopore sequencing provides a quantitative approach for river biodiversity, pollution and environmental health monitoring. This method is more cost-effective and requires less laboratory preparation time or molecular expertise (barcode/primer design) than alternative biodiversity eDNA approaches (e.g. metabarcoding or qPCR). Shotgun analysis approaches will also benefit from the continual expansion of reference genome databases, for environmental, evolutionary and medical reasons, among others. Computation, cloud and artificial intelligence (AI) tools (such as the cloud-based analyses utilized here) can analyze shotgun sequencing eDNA data in a matter of hours and can be used by conservation practitioners, environmentalists and public health personnel without the need for coding or in-depth bioinformatics skills. The proven citizen/community scientist applicability and ease of eDNA sampling may further revolutionize and democratize biodiversity research, conservation surveillance, and environmental health monitoring. Long-read shotgun sequencing of eDNA offers the means to assess whole ecosystems, and the ecological, trophic, and host-pathogen interactions occurring within them.

genomics↗

bioRxiv2024

Global overview of sea turtle fibropapillomatosis tumors: a survey of expert opinions and trends.

Marine environments offer a wealth of opportunities to improve understanding and treatment options for cancers, through insights into a range of fields from drug discovery to mechanistic insights. By applying One Health principles the knowledge obtained can benefit both human and animal populations, including marine species suffering from cancer. One such species is green sea turtles (Chelonia mydas), which are under threat from fibropapillomatosis (FP), an epizootic tumor disease (animal epidemic) that continues to spread and increase in prevalence globally. In order to effectively address this epizootic, a more thorough understanding is required of the prevalence of the disease and the approaches to treating afflicted turtles. To identify knowledge gaps and assess future needs, we conducted a survey of sea turtle FP experts. The survey consisted of 47 questions designed to assess general perceptions of FP, the areas where more information is needed, local FP trends, the disease status, and mitigation needs, and was voluntarily completed by 44 experts across a broad geographic range. The survey responses provided a valuable overview of the current FP status in sea turtles, FP research, and insight into the approaches currently taken by turtle rehabilitation facilities around the world. Over 70% of respondents both recognized FP as a cancerous panzootic disease, and reported that FP is increasing in prevalence. They report several factors contributing to this increase. Nearly all of the respondents reported that FP research, patient treatment and rehabilitation required more funding in their area, and reported inadequate facilities and capacity for dealing with FP patients. Treatment approaches varied: just over 70% of the medical experts that responded surgically remove FP tumors, either using laser or scalpel. Just under half of respondents use anti-cancer drugs in their treatment of FP. Internal tumors were reported as justification for euthanasia by 61.5% of respondents, and 30.8% reported severe external tumors to be sufficient grounds for euthanasia. Most medical respondents (93.3%) routinely perform necropsy on deceased or euthanized FP-afflicted turtles. Over 80% of respondents considered large-scale multidisciplinary collaboration extremely important for advancing the field of FP research. The survey responses provide a valuable insight into the current state of FP treatment, rehabilitation and research, and help to identify critical FP-related research and rehabilitation areas most in need of attention.

cancer biology↗

bioRxiv2022

Proteasomal downregulation of the pro-apoptotic MST2 pathway contributes to BRAF inhibitor resistance in melanoma

The RAS-RAF-MEK-ERK pathway is hyperactivated in almost all malignant melanomas, and mutations in BRAF or NRAS account for most of these cases. BRAF inhibitors are highly efficient for treating patients with BRAFV600E mutations, but tumours frequently acquire resistance within a few months. Multiple resistance mechanisms have been identified, due to mutations or network adaptations that revive ERK signalling. We have previously shown that RAF proteins inhibit the MST2 proapoptotic pathway in a kinase independent fashion. Here, we have investigated the role of the MST2 pathway in mediating resistance to BRAF inhibitors. We show that the BRAFV600E mutant protein, but not the wildtype BRAF protein, strongly binds to MST2 and inhibits MST2 pro-apoptotic signalling. Downregulation of MST2 reduces BRAF inhibitor induced apoptosis. In BRAF inhibitor resistant cell lines MST2 pathway proteins are downregulated by ubiquitination and subsequent proteasomal degradation rendering cells refractory to MST2 pathway induced apoptosis. Restoration of apoptosis can be achieved by increasing MST2 pathway protein expression using proteasome inhibitors. In summary, we show that the MST2 pathway plays a role in the acquisition of BRAF inhibitor resistance in melanoma.

molecular biology↗

bioRxiv2020

Mutational, transcriptional and viral shedding dynamics of the marine turtle fibropapillomatosis tumor epizootic

Sea turtle populations are directly and indirectly under threat from a range of anthropogenic processes. Perhaps the most visibly apparent of these is the disfiguring tumor disease epizootic (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at a number of affected sites globally. Environmental exposures seem key to inducing tumor development, possibly through weakening host immune systems to the point of enabling pathogen-induced tumor formation. However, we do not yet understand the precise molecular and mutational events driving fibropapillomatosis tumor formation and progression. Similarly, many open questions remain about the role of the herpesvirus (chelonid herpesvirus 5, ChHV5) associated with the disease as a potential co-trigger, and whether its occurrence within tumors is causative or opportunistic. Without improved understanding of the basic biology of this disease epizootic, treatment, containment and mitigation options are severely hampered. To address fundamental questions relating to the oncogenic signaling, mutational spectrum, viral load, viral transcriptional status (lytic or latent) and spread, we employed transcriptomic profiling, whole genome sequencing, immunohistochemistry and environmental (e)DNA-based monitoring of viral shedding. In particular we focused on the mutational landscape of tumors and assessing the transcriptional similarity of external (skin) and internal (visceral organs) tumors, and the oncogenic signaling events driving early stage tumor growth and post-surgical tumor regrowth. These analyses revealed that internal fibropapillomatosis tumors are molecularly distinct from the more common external tumors. However, our molecular analyses also revealed that there are a small number of conserved potentially therapeutically targetable molecular vulnerabilities in common between internal and external tumors, such as the MAPK, Wnt, TGF{beta} and TNF oncogenic signaling pathways. We also determined that the tumor genomes can harbor copy number gains, indicating potentially viral-independent oncogenic processes. Genes within such mutated genomic regions have known roles in human skin cancer, including MAPK-associated genes. Turtles attempt to mount an immune response, but in some animals this appears to be insufficient to prevent tumor development and growth. ChHV5 was transcriptionally latent in all tumor stages sequenced, including early stage and recurrent tumors. We also revealed that the tumors themselves are the primary source of viral shedding into the marine environment and, if they are surgically removed, the level of ChHV5 in the water column drops. Together, these results offer an improved understanding of fibropapillomatosis tumorigenesis and provide insights into the origins, therapeutic treatment, and appropriate quarantine responses for this wildlife epizootic. Furthermore, they provide insights into human pathogen-induced cancers, particularly mechanisms which are difficult to study in the human and terrestrial context, such as time-course quantification-based monitoring of viral shedding.

cancer biology↗