bioRxiv Science⌕ Search

Biology subjects

Fraser, D. J.

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

9 recordsLinked to original sources

eDNA provides accurate and precise estimates of abundance by integrating bioenergetics and particle mass-balance

Anthropogenic activities have led to an unprecedented crisis in freshwater biodiversity loss. The capacity to monitor the abundance of wild populations is critical to conserving biodiversity, but conventional physical specimen collection methods are invasive, costly, and labour-intensive. Environmental DNA (eDNA) offers a promising alternative, being easy to sample, with studies under controlled laboratory conditions showing consistent correlations between eDNA concentration and abundance. However, applying eDNA to monitor abundance remains contentious, as eDNA particle dynamics and the ecology of eDNA production can decouple this relationship in natural ecosystems. To address this, we provide a novel modeling method to produce population estimates from eDNA. We integrated bioenergetics and mass-balance frameworks to relate eDNA concentrations to freshwater fish population abundance estimated through conventional mark-recapture in Brook Trout (Salvelinus fontinalis) across nine Rocky Mountains lakes, five of which underwent size-selective harvesting over two years. Our integrated framework improved the variance explained in eDNA concentrations from 24% to 71%. The integrated model accurately distinguished most (94%) abundance estimates across populations and sampling periods, detecting both natural and harvest-induced reductions in abundance within several populations. This study is the first to empirically integrate the DNA production mechanism and particle dynamics and provide a new methodological approach enabling rapid and accurate abundance quantification. We also discuss how this new tool can be integrated in existing monitoring programs.

ecology↗

Dextrin conjugation to colistin inhibits its toxicity, cellular uptake and acute kidney injury in vivo.

The acute kidney injury (AKI) and dose-limiting nephrotoxicity, which occurs in 20-60% of patients following systemic administration of colistin, represents a challenge in the effective treatment of multi-drug resistant gram-negative infections. To reduce clinical toxicity of colistin and improve targeting to infected /inflamed tissues, we previously developed dextrin-colistin conjugates, whereby colistin is designed to be released by amylase-triggered degradation of dextrin in infected and inflamed tissues, after passive targeting by the enhanced permeability and retention effect. Whilst it was evident in vitro that polymer conjugation can reduce toxicity and prolong plasma half-life, without significant reduction in antimicrobial activity of colistin, it was unclear how dextrin conjugation would alter cellular uptake and localisation of colistin in renal tubular cells in vivo. We discovered that dextrin conjugation effectively reduced colistins toxicity towards human kidney proximal tubular epithelial cells (HK-2) in vitro, which was mirrored by significantly less cellular uptake of Oregon Green (OG)-labelled dextrin-colistin conjugate, when compared to colistin. Using live-cell confocal imaging, we revealed localisation of both, free and dextrin-bound colistin in endolysosome compartments of HK-2 and NRK-52E cells. Using a murine AKI model, we demonstrated dextrin-colistin conjugation dramatically diminishes both proximal tubular injury and renal accumulation of colistin. These findings reveal new insight into the mechanism by which dextrin conjugation can overcome colistins renal toxicity and show the potential of polymer conjugation to improve the side effect profile of nephrotoxic drugs. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=126 SRC="FIGDIR/small/565265v1_ufig1.gif" ALT="Figure 1"> View larger version (42K): org.highwire.dtl.DTLVardef@1ec6ac8org.highwire.dtl.DTLVardef@56a2b1org.highwire.dtl.DTLVardef@1d347fborg.highwire.dtl.DTLVardef@1ab7da_HPS_FORMAT_FIGEXP M_FIG C_FIG

pharmacology and toxicology↗

Vive la difference: why, how, and what trait combinations improve functional community ecology

Analyses of functional trait variation across ecological communities offer valuable insights into the factors that influence and predict trait composition, deepening our understanding of community structure. These analyses also shed light on patterns of trait dispersion, including underdispersion and overdispersion, which are often linked to the mechanisms underlying community assembly. However, striking a balance between characterizing complex phenotypes through the integration of comprehensive set of traits while ensuring the preservation of the distinct signals of overdispersion and underdispersion can pose significant challenges. This is because some trait combinations can result in high functional dispersion or overdispersion, while others may lead to underdispersion within the same community. In this study, we provide a rationale for the importance of trait selection in community ecology and develop a framework that optimizes patterns of functional trait variation among communities. We explored the responses of six trait sets along large-scale environmental gradients, using [~]700 lake-fish communities in Ontario (Canada). We started by adopting the conventional approaches of combining all traits as well as leveraging prior knowledge in fish biology to group traits that are functionally related (Diet, Morphology, Temperature Preference). We contrasted these approaches with a novel computational method to select combinations of traits that maximise overdispersion and minimise underdispersion. We found that separating traits according to their functions or by their patterns revealed signals in communities that appeared random when all the traits were pooled together. Combining our computational approach with environmental models revealed that functional patterns could be very well explained by multiple environmental predictors (model R2 up to 0.7). Our study also outlines future selection procedures to further uncover more complex patterns of species associations based on their traits.

ecology↗

Global assessment of effective population sizes: consistent taxonomic differences in meeting the 50/500 rule

Effective population size (Ne) is a particularly useful metric for conservation as it affects genetic drift, inbreeding and adaptive potential within populations. Current guidelines recommend a minimum Ne of 50 and 500 to avoid short-term inbreeding and to preserve long-term adaptive potential, respectively. However, the extent to which wild populations reach these thresholds globally has not been investigated, nor has the relationship between Ne and human activities. Through a quantitative review, we generated a dataset with 4145 georeferenced Ne estimates from 3576 unique populations, extracted from 712 articles. These data show that certain taxonomic groups are less likely to meet 50/500 thresholds and are disproportionately impacted by human activities; plant, mammal, and amphibian populations had a [&le;]52% probability of reaching[N] e = 50 and a <5% probability of reaching[N] e = 500. Populations listed as being of conservation concern according to the IUCN Red List had a lower[N] e than unlisted populations, and this relationship held true across all taxonomic groups.[N] e was reduced in areas with a greater Global Human Footprint, especially for amphibians and mammals, however relationships varied between taxa. We also highlight several considerations for future works estimating[N] e, including the role that gene flow and subpopulation structure plays in the estimation of[N] e in wild populations, and the need for finer-scale taxonomic analyses. Our findings provide guidance for more specific thresholds based on Ne and help prioritize assessment of populations from taxa most at risk of failing to meet conservation thresholds.

evolutionary biology↗

Macrogenetics reveals multifaceted influences of environmental variation on vertebrate population genetic diversity across the Americas

Relative to species diversity gradients, the broad scale distribution of population-specific genetic diversity (PGD) across taxa remains understudied. We used nuclear DNA data collected from 6285 vertebrate populations across the Americas to assess the role environmental variables play in structuring the spatial/latitudinal distribution of PGD, a key component of adaptive potential in the face of environmental change. Our results provide key evidence for taxa-specific responses and that temperature variability in addition to mean temperature may be a primary driver of PGD. Additionally, we found some positive influence of precipitation, productivity, and elevation on PGD; identified trends were dependent on the metric of PGD. In contrast to the classic negative relationship between species diversity and latitude, we report either a positive or taxa-dependent relationship between PGD and latitude, depending on the metric of PGD. The inconsistent latitudinal gradient in different metrics of PGD may be due to opposing processes diminishing patterns across latitudes that operate on different timescales, as well as the flattening of large-scale genetic gradients when assessing across species versus within species. Our study highlights the nuance required to assess broad patterns in genetic diversity, and the need for developing balanced conservation strategies that ensure population, species, and community persistence.

ecology↗

Single generation exposure to a captive diet: a primer for domestication selection in a salmonid fish?

Millions of wild animals in captivity are reared on diets that differ in their uptake and composition from natural conditions. Few studies have investigated whether such novel diets elicit unintentional domestication selection in captive rearing and supplementation programs. In highly fecund salmonid fishes, natural and captive mortality is highest in the first few months of exogenous feeding. This high early mortality might be a potent driver of unintentional selection because wild fish normally forage on live prey whereas they are fed almost exclusively pellet feed in captivity: fish that do not adapt pellet feed well under captive conditions experience reduced growth and/or die. We tested this hypothesis by generating a large number of families from F1 captive and wild fish originating from the same three populations and then rearing them each on pellet and natural, live, drifting feed for three months at the beginning of exogenous feeding. We found that captive fish of every population grew faster than wild fish in all diet treatments. Populations exhibited an idiosyncratic response to diet treatment, with two populations exhibiting faster growth on a pellet diet versus the natural diet but another population exhibiting similar growth in both diet treatments. Fish exposed to a natural diet also exhibited higher survival relative to those given a pellet diet. Captive and wild fish did not differ in survival, regardless of population of origin. Overall, we found evidence that rapid domestication selection associated with a single generation exposure to a novel captive diet generates genetically-based changes to individual fitness (e.g., growth and survival) in a wild fish.

evolutionary biology↗

Allometric scaling strengthens the relationship between eDNA particle concentration and organism abundance in nature

Organism abundance is a critical parameter in ecology, but its estimation is often challenging. Approaches utilizing eDNA to indirectly estimate abundance have recently generated substantial interest. However, preliminary correlations observed between eDNA concentration and abundance in nature are typically moderate in strength with significant unexplained variation. Here we apply a novel approach to integrate allometric scaling coefficients into models of eDNA concentration and organism abundance. We hypothesize that eDNA particle production scales non-linearly with mass, with scaling coefficients < 1. Wild populations often exhibit substantial variation in individual body size distributions; we therefore predict that the distribution of mass across individuals within a population will influence population-level eDNA production rates. To test our hypothesis, we collected standardized body size distribution and mark-recapture abundance data using whole-lake experiments involving nine populations of brook trout. We correlated eDNA concentration with three metrics of abundance: density (individuals/ha), biomass (kg/ha), and allometrically scaled mass (ASM) ({sum}(individual mass0.73)/ha). Density and biomass were both significantly positively correlated with eDNA concentration (adj. R2 = 0.59 and 0.63, respectively), but ASM exhibited improved model fit (adj. R2 = 0.78). We also demonstrate how estimates of ASM derived from eDNA samples in unknown systems can be converted to biomass or density estimates with additional size structure data. Future experiments should empirically validate allometric scaling coefficients for eDNA production, particularly where substantial intraspecific size distribution variation exists. Incorporating allometric scaling may improve predictive models to the extent that eDNA concentration may become a reliable indicator of abundance in nature.

ecology↗

Size reductions and genomic changes associated with harvesting within two generations in wild walleye populations

The extent and rate of harvest-induced genetic changes in natural populations may impact population productivity, recovery and persistence. While there is substantial evidence for phenotypic changes in harvested fishes, knowledge of genetic change in the wild remains limited, as phenotypic and genetic data are seldom considered in tandem, and the number of generations needed for genetic changes to occur is not well understood. We quantified changes in size-at-age, sex-specific changes in body size, and genomic metrics in three harvested walleye (Sander vitreus) populations and a fourth reference population with low harvest levels over a 15-year period in Mistassini Lake, Quebec. We also collected Traditional Ecological Knowledge (TEK) surrounding concerns about these populations over time. Using [~]9000 SNPs, genomic metrics included changes in population structure, neutral genomic diversity, effective population size and signatures of selection. TEK revealed concerns about overall reductions in body size and number of fish caught. Smaller body size, smaller size-at-age, changing population structure (population differentiation within one river and homogenization between two others), and signatures of selection between historical and contemporary samples reflected coupled phenotypic and genomic change in the three harvested populations in both sexes, while no change occurred in the reference population. Sex-specific analyses revealed differences in both body size and genomic metrics but were inconclusive about whether one sex was disproportionately affected. Our results support that harvest-induced genetic changes can arise within 1-2.5 generations in long-lived wild fishes, demonstrating the need to investigate concerns about harvest-induced evolution quickly once they have been raised.

ecology↗

Comparing low-pass sequencing and genotyping for trait mapping in pharmacogenetics

Low pass sequencing has been proposed as a cost-effective alternative to genotyping arrays to identify genetic variants that influence multifactorial traits in humans. For common diseases this typically has required both large sample sizes and comprehensive variant discovery. Genotyping arrays are also routinely used to perform pharmacogenetic (PGx) experiments where sample sizes are likely to be significantly smaller, but clinically relevant effect sizes likely to be larger. To assess how low pass sequencing would compare to array based genotyping for PGx we compared a low-pass assay (in which 1x coverage or less of a target genome is sequenced) along with software for genotype imputation to standard approaches. We sequenced 79 individuals to 1x genome coverage and genotyped the same samples on the Affymetrix Axiom Biobank Precision Medicine Research Array (PMRA). We then down-sampled the sequencing data to 0.8x, 0.6x, and 0.4x coverage, and performed imputation. Both the genotype data and the sequencing data were further used to impute human leukocyte antigen (HLA) genotypes for all samples. We compared the sequencing data and the genotyping array data in terms of four metrics: overall concordance, concordance at single nucleotide polymorphisms in pharmacogenetics-related genes, concordance in imputed HLA genotypes, and imputation r2. Overall concordance between the two assays ranged from 98.2% (for 0.4x coverage sequencing) to 99.2% (for 1x coverage sequencing), with qualitatively similar numbers for the subsets of variants most important in pharmacogenetics. At common single nucleotide polymorphisms (SNPs), the mean imputation r2 from the genotyping array was 90%, which was comparable to the imputation r2 from 0.4x coverage sequencing, while the mean imputation r2 from 1x sequencing data was 96%. These results indicate that low-pass sequencing to a depth above 0.4x coverage attains higher power for trait mapping when compared to the PMRA.

genetics↗