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Parsons, K. M.

Publications and source records attributed to Parsons, K. M..

9 recordsLinked to original sources

Fifteen-year microbiome survey of endangered killer whales (Orcinus orca) reveals declining diversity and population differences

The endangered Southern Resident killer whale (Orcinus orca) (SRKW) population is burdened by multiple anthropogenic stressors with limited non-invasive approaches for health surveillance. The gut microbiome is interconnected with host physiology and can be characterized using remotely collected fecal samples, creating unique opportunities to integrate environmental and individualized host-associated features of health. In this study, we used fecal samples collected over a 15-year period (2005-2019) from 77% of the living, wild SRKW population (56 individuals, 1-17 time points per individual), as well as fecal samples from the conspecific Northern and Alaska Resident killer whale populations, to characterize distal gut microbiota structure and genomic composition. SRKW microbiotas were individualized and distinct from those of the nearby Northern and Alaska Resident populations, both of which exhibit consistently higher fecundity and survivorship. During the study period, SRKW fecal microbiota species richness declined, despite stability over periods of time less than or equal to 1 year. Several potential bacterial pathogens, such as Fusobacterium spp., achieved dominance in the fecal microbiotas of SRKW individuals sampled within 6 months of death. These findings demonstrate the feasibility and value of harnessing non-invasively collected fecal samples and microbiome profiles for longitudinal killer whale health surveillance.

microbiology↗

Quantitative, Multispecies Monitoring at a Continental Scale

Molecular data from environmental samples can reflect the abundance of species DNA, an index immediately relevant to natural-resources management at a broad geographic scale. These data commonly derive from assays designed and targeted for individual species (e.g., using qPCR or ddPCR), or from metabarcoding that use more general PCR primers to amplify many species simultaneously. Multispecies analyses make efficient use of field samples and laboratory time, and speak to inherently multispecies questions of management and ecological interest. However, unlike single-species techniques, metabarcoding alone generally reflects only the environmental DNA (eDNA) proportions of target-species DNA present, not their absolute quantities. Here, we combine qPCR and metabarcoding data derived from the same samples to estimate quantities of eDNA from many fish species along the US West Coast in three dimensions, demonstrating a technique of practical relevance for both management and ecology. We derive spatially explicit maps of eDNA abundances for 12 common species of ecological and management importance and point the way to quantitative surveys of wild species using molecules alone. We find that species distribution maps derived from eDNA largely mirror known species niches and known spatial distributions. Notably, our analyses indentify biodiversity hotspots that align with previously documented regions of ecological significance, such as the Columbia River plume and the Heceta Bank.

ecology↗

Differential Decay of Multiple eNA Components from a Cetacean

Environmental nucleic acids (eNA), such as DNA and RNA, are powerful tools for monitoring biodiversity. Yet, interpreting eNA detections requires understanding of their environmental persistence. We conducted a decay experiment using seawater from an open enclosure to track degradation of six eNA components derived from Tursiops truncatus: mitochondrial eDNA of varying lengths, ribosomal eRNA, and messenger eRNA. Targets were quantified over seven days via digital droplet PCR (ddPCR). Decay followed a biphasic exponential model with rapid initial loss ([~]24 hours at 15 {degrees}C), followed by slower degradation. Cytb messenger eRNA was least stable, disappearing within four hours. Ribosomal eRNA persisted longer but degraded slightly faster than its eDNA counterpart ({lambda} = 0.236 vs. 0.165 hr-{superscript 1}). Longest eDNA fragments decayed more rapidly ({lambda} = 0.190 hr-1) than shorter ones ({lambda} = 0.114 hr-1). These findings support the use of eDNA fragment length as a proxy for degradation state and reinforce that combining multiple eNA components with distinct stabilities can potentially provide a molecular clock for inferring eNA age. This approach improves the spatiotemporal resolution of eNA-based monitoring, particularly for rare marine-mammal that act as point sources. We also emphasize the importance of explicitly distinguishing between RNA types (ribosomal vs. messenger) in environmental studies, given their divergent stability and interpretability.

molecular biology↗

Widespread parasite infections in living resident killer whales in the Northeast Pacific Ocean

Multiple populations of resident ecotype killer whales (Orcinus orca ater) inhabit the Northeast Pacific, but the southern resident killer whale (SRKW) population is the most at-risk. SRKWs were listed as endangered in the United States in 2005 and have since shown little sign of recovery. Several factors have been identified as key threats to this population, and previously published studies suggest the population may be energetically stressed. Underlying health risks, such as parasitism, may be contributing to this populations failure to recover, but little is known about parasite infections in living individuals from natural killer whale populations. To assess the prevalence of internal parasite infections in Northeastern Pacific killer whales, we examined scat from endangered SRKW (n = 25) compared to two conspecific populations of resident killer whales that are not in decline: northern resident (NRKW, n = 2) and southern Alaska resident killer whales (SARKW, n = 7), and one offshore killer whale (OKW, n = 1). We analyzed 35 fecal samples collected from 27 wild killer whales using both microscopic identification of parasite eggs and genetic detection of parasites through DNA metabarcoding. We used body condition indices derived from concurrent aerial photogrammetry to evaluate whether parasite infection status was associated with individual body condition. We found that most individuals sampled (94%) were positive for Anisakis spp. - a parasitic nematode known to inhabit the intestines of cetaceans. These infections were detected across populations, and were not correlated with body condition, based on limited paired data. These results suggest that Anisakis infection is widespread among resident killer whales of the Northeast Pacific. The widespread detections of Anisakis among the samples examined here emphasizes the need for further work to understand the potential health impacts of parasitic infections on individual killer whales, and potential synergistic effects with other environmental stressors.

ecology↗

Distinguishing Signal from Noise: Understanding Patterns of Non-Detections to Inform Accurate Quantitative Metabarcoding

Correcting for amplification biases in genetic metabarcoding data can yield quantitative estimates of template DNA concentrations. However, a major source of uncertainty in metabarcoding data is the presence of non-detections, where a technical PCR replicate fails to detect a species observed in other replicates. Such non-detections are an important special case of variability among technical replicates in metabarcoding data, particularly in environmental samples. While many sampling and amplification processes underlie observed variation in metabarcoding data, understanding the causes of non-detections is an important step in distinguishing signal from noise in metabarcoding studies. Here, we use both simulated and empirical data to 1) develop a qualitative understanding of how non-detections arise in metabarcoding data, 2) outline steps to recognize uninformative data in practice, and 3) identify the conditions under which amplicon sequence data can reliably detect underlying biological signals. We show in both simulations and empirical data that, for a given species, the rate of non-detections among technical replicates is a function of both the template DNA concentration and species-specific amplification efficiency. Consequently, we conclude metabarcoding datasets are strongly affected by (1) deterministic amplification biases during PCR and (2) stochastic sampling of amplicons during sequencing -- both of which we can model -- but also by (3) stochastic sampling of rare molecules prior to PCR, which remains a frontier for quantitative metabarcoding. Our results highlight the importance of estimating species-specific amplification efficiencies and critically evaluating patterns of non-detection in metabarcoding datasets to better distinguish environmental signal from the noise inherent in molecular detections of rare targets.

molecular biology↗

Message in a Bottle: Archived DNA Reveals Marine Heatwave-Associated Shifts in Fish Assemblages

Marine heatwaves can drive large-scale shifts in marine ecosystems but studying their impacts on whole species assemblages can be difficult. Here, we leverage the taxonomic breadth and resolution of DNA sequences derived from environmental DNA (eDNA) in the ethanol of a set of 23-year longitudinal ichthyoplankton samples, combining these with microscopy-derived ichthyoplankton identification to yield higher-resolution, species-specific quantitative abundance estimates of fish assemblages in the California Current Large Marine Ecosystem during and after the 2014-16 Pacific marine heatwave. This integrated dataset reveals patterns of tropicalization with increases in southern, mesopelagic species and associated declines in important temperate fisheries targets (e.g., North Pacific Hake (Merluccius productus) and Pacific Sardine (Sardinops sagax)). We observed novel assemblages of southern, mesopelagic fishes and temperate species (e.g., Northern Anchovy, Engraulis mordax) even after the return to average water temperatures. Our innovative preservative derived eDNA metabarcoding and quantitative modeling approaches open the door to reconstructing the historical dynamics of assemblages from modern and archived samples worldwide. SummaryNovel quantitative abundance estimates from archived DNA reveals marine heatwave-associated shifts in fish assemblages.

ecology↗

DNA Methylation Networks Underlying Mammalian Traits

Epigenetics has hitherto been studied and understood largely at the level of individual organisms. Here, we report a multi-faceted investigation of DNA methylation across 11,117 samples from 176 different species. We performed an unbiased clustering of individual cytosines into 55 modules and identified 31 modules related to primary traits including age, species lifespan, sex, adult species weight, tissue type and phylogenetic order. Analysis of the correlation between DNA methylation and species allowed us to construct phyloepigenetic trees for different tissues that parallel the phylogenetic tree. In addition, while some stable cytosines reflect phylogenetic signatures, others relate to age and lifespan, and in many cases responding to anti-aging interventions in mice such as caloric restriction and ablation of growth hormone receptors. Insights uncovered by this investigation have important implications for our understanding of the role of epigenetics in mammalian evolution, aging and lifespan.

evolutionary biology↗

Nuclear stabilisation of p53 requires a functional nucleolar surveillance pathway

The nucleolar surveillance pathway (NSP) monitors nucleolar fidelity and responds to nucleolar stresses (i.e., inactivation of ribosome biogenesis) by mediating the inhibitory binding of ribosomal proteins (RPs) to mouse double minute 2 homolog (MDM2), a nuclear-localised E3 ubiquitin ligase, which results in p53 accumulation. Inappropriate activation of the NSP has been implicated in the pathogenesis of collection of human diseases termed "ribosomopathies", while drugs that selectively activate the NSP are now in trials for cancer. Despite the clinical significance, the precise molecular mechanism(s) regulating the NSP remain poorly understood. Using genome-wide loss of function screens, we demonstrate the ribosome biogenesis (RiBi) axis as the most potent class of genes whose disruption stabilises p53. Furthermore, we identified a novel suite of genes critical for the NSP, including a novel mammalian protein implicated in 5S ribonucleoprotein particle (5S-RNP) biogenesis, HEATR3. By selectively disabling the NSP, we unexpectedly demonstrate that a functional NSP is required for the ability of all nuclear acting stresses tested, including DNA damage, to robustly induce p53 accumulation. Together, our data demonstrates that the NSP has evolved as the dominant central integrator of stresses that regulate nuclear p53 abundance, thus ensuring RiBi is hardwired to cellular proliferative capacity.

cell biology↗

Cohesin mutations are synthetic lethal with stimulation of WNT signaling

Mutations in genes encoding subunits of the cohesin complex are common in several cancers, but may also expose druggable vulnerabilities. We generated isogenic MCF10A cell lines with deletion mutations of genes encoding cohesin subunits SMC3, RAD21 and STAG2 and screened for synthetic lethality with 3,009 FDA-approved compounds. The screen identified several compounds that interfere with transcription, DNA damage repair and the cell cycle. Unexpectedly, one of the top hits was a GSK3 inhibitor, an agonist of Wnt signaling. We show that sensitivity to GSK3 inhibition is likely due to stabilization of {beta}-catenin in cohesin mutant cells, and that Wnt-responsive gene expression is highly sensitized in STAG2-mutant CMK leukemia cells. Moreover, Wnt activity is enhanced in zebrafish mutant for cohesin subunit rad21. Our results suggest that cohesin mutations could progress oncogenesis by enhancing Wnt signaling, and that targeting the Wnt pathway may represent a novel therapeutic strategy for cohesin mutant cancers.

cancer biology↗