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Ferguson, S.

Publications and source records attributed to Ferguson, S..

At least 19 recordsLinked to original sources

Lineage-specific expansion of a potential novel class of resistance genes in Myrtaceae

Genes encoding intracellular nucleotide-binding site leucine-rich repeat (NBS-LRR) receptors represent the largest class of resistance (R) genes in plants, yet their evolutionary trajectory in trees remains poorly understood. Using high-quality long-read genome assemblies from eight Myrtaceae species, we identified 15,792 NBS-encoding genes with threefold variation in gene content across species. To investigate potential decoy domains for effector proteins of pathogens, we parsed the annotated NBS-encoding genes and determined 181 unique non-canonical domains. Notably, we observed frequent integration of Jacalin domains into TIR-NBS proteins. This novel gene family, named TNJ, is hypothesized to represent a new R gene class. Further exploration of TNJ sequence analysis shows up to seven Jacalin domains per protein and forming a monophyletic clade; however, AF3 modelling confirmed only six domains. Conserved residues in the TIR domain and functional motifs within the NB-ARC domain supports TNJs potential role in immune signalling. Most hypervariable sites and positively selected sites detected to be surface-exposed were clustered in the Jacalin region of TNJ, suggesting that surfaces of Jacalin domain may harbour residues determining pathogen recognition specificity. These findings support TNJ as a potentially new class of R genes in Myrtaceae with Jacalin as a replacement for LRR.

evolutionary biology↗

Habitat discontinuity and fidelity to migratory routes shape narwhal genetic structure and diversity

Rapid Arctic warming is reshaping marine ecosystems and altering the evolutionary trajectories of ice-associated species. Narwhals (Monodon monoceros) are Arctic endemics that are thought to be vulnerable to climate change. We present the first nuclear genomic assessment of narwhals across their distribution to evaluate population structure, demographic history, local adaptation, inbreeding and genetic load. Using genomes from 117 individuals, we identified three populations: Canadian Arctic Archipelago/West Greenland, Northeast Greenland/Svalbard and Southeast Greenland. Demographic reconstructions indicated low effective population size over at least 600,000 years, followed by population growth during the last glacial period. Our results suggest that population structure is maintained by habitat discontinuities and fidelity to migration routes. The latter may promote local adaptation, as genes related to long-term memory were found in regions putatively under selection in Canadian Arctic Archipelago/West Greenland narwhals, which undertake the longest migrations. Genome-wide diversity was uniformly low across populations. Inbreeding levels were inversely related to estimated population sizes. The small and rapidly declining Southeast Greenland population exhibited elevated recent inbreeding. Deleterious mutations were primarily masked in heterozygous genotypes, raising concerns for this population. Together, our results demonstrate that past climate, habitat discontinuities and migration fidelity jointly structure narwhal populations.

evolutionary biology↗

Cytotoxicity of Pelargonic Acid and Its Commercial Formulation Roundup NL (Glyphosate-Free Roundup)

Evidence of negative health and environmental effects of glyphosate-based herbicides (GBHs) has led to marketing of glyphosate-free formulations. A frequent glyphosate replacement is pelargonic acid, which is rapidly degraded, leading to claims of greater safety and less environmentally damaging than GBHs. However, toxicity of commercial pelargonic acid formulations containing several co-formulants have not been determined. Using Roundup NL, a representative pelargonic acid-based herbicide, we undertook tissue culture cell assays measuring viability, plasma membrane integrity, DNA damage, and activation of stress-response pathways. In human hepatoma HepG2 cells, Roundup NL was more cytotoxic than pelargonic acid, and more toxic than the GBH Roundup ProBio and glyphosate as shown by reduced viability underpinned by plasma membrane damage. Pelargonic acid and Roundup NL did not induce oxidative stress. However, comet assays revealed that pelargonic acid but not Roundup NL caused a modest but significant increase in DNA damage at sub-cytotoxic concentrations. The murine embryonic stem cell-based ToxTracker system confirmed Roundup NL as not directly genotoxic but triggered oxidative stress and protein damage (ER stress, impaired proteostasis) indicating cell and assay dependency of oxidative stress pathway activation. Our results suggest that exposure to pelargonic acid-based herbicides constitutes a health hazard and that co-formulants present in Roundup NL contribute substantially to its overall toxicity.

pharmacology and toxicology↗

IDENTIFICATION OF HUMAN PHOTORECEPTORS SUITABLE FOR CELL REPLACEMENT STUDIES IN A PRECLINICAL ACHROMATOPSIA MODEL

Cell replacement represents a potential treatment modality for retinal disorders characterized by photoreceptor loss. However, photoreceptor replacement approaches have not been clinically established. To take this forward, the main goal of this study was to systematically compare human photoreceptors of different ages and identify those that enable functional integration into the degenerative retina. Donor cells were isolated from iPSC-derived retinal organoids generated by a GMP-compliant protocol at differentiation days 120, 150, or 200 and transplanted subretinally into cone photoreceptor function loss 1 (Cpfl1) recipients, an inherited mouse model of cone degeneration. While younger photoreceptors showed slightly improved transplantation outcomes, donor photoreceptors of all culture stages displayed long-term survival, cone identity, structural integration into the host retina, and tight interactions with host Muller glia, including formation of a continuous outer limiting membrane. Transplanted photoreceptors showed signs of advanced maturation, including correct polarization with generation of apical inner- and outer segments, while basal synapses were formed with host bipolar cells. Electrophysiological assessment of host retinal ganglion cells revealed light-evoked responses in transplant-containing regions, providing evidence for functional incorporation of human photoreceptors into the mouse neuro-retinal circuitry. Thus, GMP-compliant human iPSC-derived photoreceptors are stable over a wide range of differentiation stages and constitute a robust cell source for retinal transplantation and functional repair. The findings provide important prerequisites for the development of standardized procedures towards clinical translation of photoreceptor replacement in the retina. Significant statementCell transplantation represents a potential therapy for retinal dystrophies. However, conditions allowing stable functional integration and maturation of donor photoreceptors have not been defined. We systematically compared GMP-compliant iPSC-derived photoreceptors of different culture times after transplantation into a retinal degeneration mouse model. Photoreceptors of all ages showed structural integration and advanced maturation in close interaction with host Muller glia and bipolar cells, allowing restoration of light-driven responses. Thus human photoreceptors isolated from retinal organoids represent a robust source for clinical development of cell replacement in the diseased retina.

neuroscience↗

Calsyntenin-1 and calsyntenin-3 coordinate TGN exit of axonal cargoes

Neurons rely on precise biosynthetic protein transport from the soma to the axon and dendrites. Brain-enriched calsyntenins (CSTN1-3) are unique transmembrane adaptors that link cargo to kinesin-1 for transport. Yet, the neuronal distribution and interdependence of the three CSTN paralogs remain unclear. Here, we dissected their subcellular localization and contribution to biosynthetic protein transport. CSTN paralogs were predominantly localized to the TGN and axonal vesicles, with CSTN1 and CSTN3 showing higher expression levels than CSTN2. Depletion of either CSTN1 or CSTN3 affected axonal abundance of the other, suggesting that they function within the same pathway. Consistently, knockdown of CSTN1 or CSTN3, but not CSTN2, impaired the TGN exit and transport of multiple biosynthetic cargoes to the axon. Interestingly, most CSTN-positive vesicles exiting the TGN and in the axon were marked by the biosynthetic trafficking regulator RAB6A. Furthermore, we identified opposing, paralog-specific roles of CSTN1 and CSTN3 in regulating RAB6A levels at the TGN, thereby contributing to Golgi organization and axonal trafficking. Loss of CSTN1 reduced RAB6A and induced Golgi compaction, whereas loss of CSTN3 increased RAB6A and promoted Golgi dispersal. Together, we reveal that CSTN1 and CSTN3 have distinct, yet intersecting roles in the regulation of biosynthetic axonal transport.

Cell Biology↗

A Pan-pangenome illuminates complex structural variation and selection in humans, chimpanzees, and bonobos

Complete, haplotype-resolved genome assemblies have provided unprecedented insight into the evolution of structurally complex, rapidly evolving regions of human genomes1-6; however, population-scale pangenome resources of our closest relatives, chimpanzees and bonobos (genus, Pan), are necessary to ascertain the origins and evolutionary context of these loci. Here, we sequence and assemble 58 haplotypes from four distinct Pan clades to high contiguity (median contig NG50=54 Mb), including eight near-T2T genomes. These genomes reveal previously intractable genetic variation increasing estimates of genome-wide genetic diversity 6-37% across populations compared to short-read estimates7. We identify recurrent structural polymorphisms across species impacting genes associated with immune response and host-pathogen interaction and find that structural variants (SVs) are 170- to 260-fold more likely than single nucleotide variants (SNVs) to exhibit high-impact effects across species. Contrasting SV patterns across primates we find that transposable element mutation rates differ by as much as threefold between species. We show that human disease-associated short tandem repeat (TR) loci have uniquely expanded in humans sensitizing our species to these TR-expansion disorders. Physically phased haplotypes enable reconstruction of genome-wide genealogical histories, uncovering ancient, functional genetic variation maintained by balancing selection, as well as signatures of recent adaptation in chimpanzee subspecies. Several malaria-associated loci exhibit ancient structural polymorphism, including the African great ape-specific glycophorin (GYP) gene expansion. We characterize the sequence, structure, and composition of diverse glycophorin haplotypes in humans and chimpanzees. We identify independent malaria-protective GYPA-B fusion events in humans and novel chimpanzee glycophorin genes resulting from both ancient and recent fusion events demonstrating parallel adaptations to pathogen resistance across hominins. Together, our resource highlights the critical importance of nonhuman primate population-scale pangenomics for understanding the evolution of complex genome structures and the biodiversity of our endangered closest living relatives.

evolutionary biology↗

Complex Genomic Structural Variation Underlies Climate Adaptation among Eucalyptus species

Climate change threatens global natural forest ecosystems, however, our limited understanding of adaptive genomic variation in wild forest trees restricts our ability to address this threat. Eucalyptus species likely harbour many climate adaptive alleles considering their long-standing evolutionary success across the Australian continent, yet their complex genomic variation and adaptive implications remain undercharacterised. Here, we present a comprehensive pangenome analysis of Eucalyptus viminalis using haplotype-resolved genomes and population-level long-read sequencing spanning the species natural distribution. We discovered complex and simple structural variants (SVs) that doubled the haploid genome length (530 Mbp haploid to 1.1 Gbp pan-genome). Landscape genomic analyses with SVs identified CHILL1, a 400-kb cold-adaptation locus underlined by complex structural variation. Validation across 434 accessions from three Eucalyptus species confirmed the large-effects of CHILL1, which outperforms species classification at predicting cold adaptation. These findings demonstrate that wild tree populations harbour critical adaptive alleles that can expedite climate-informed restoration.

genomics↗

Exploring contemporary and historic effective population sizes in Atlantic beluga whale populations

Ongoing global environmental changes will require animals to adapt to new conditions, as their necessary resources for survival may shift or decline. Understanding population dynamics in wildlife informs conservation strategies by providing context for genetic diversity and current population abundances. Here, we use whole genome data to reconstruct past demographic trends and estimate contemporary effective population sizes in the beluga whale (Delphinapterus leucas), an Arctic endemic species with significant cultural importance, that is an integral part of the marine ecosystem along the Canadian coast. In line with previous work, we identified six genetic populations: 1) St. Lawrence Estuary, 2) Eastern High Arctic, 3) James Bay, 4) Cumberland Sound, 5) Hudson Bay-Strait Complex and 6) Little and Great Whale Rivers. Demographic history in the deep (up to 1,000,000 years) past revealed all but the Hudson Bay-Strait Complex population declined in effective population sizes following the last glacial period. Within the last several centuries, the Eastern High Arctic and Hudson Bay-Strait Complex populations have shown evidence for an increase in effective population size and have contemporary estimates greater than 2,000. The other four populations have contemporary estimates below 400. The very low effective population size estimates in Cumberland Sound, Little and Great Whale Rivers and James Bay, as well as the high inbreeding in the St. Lawrence Estuary indicate that these populations are in need of protective measures for long-term sustainability. These results have advanced our understanding of the dynamics of beluga genetics across eastern Canada and provide valuable metrics for conservation strategies.

evolutionary biology↗

Rapid turnover and recurrent structural variation at the 17q21.31 locus in modern and ancient human genomes, and primates

The 17q21.31 locus in humans harbors several complex structural haplotypes including a [~]970kb inversion. Different inversion haplotypes have been associated with susceptibility to microdeletions causing Koolen-de Vries syndrome and variation in fecundity and recombination rates. Here, using 210 haplotype-resolved human genome assemblies and pangenome graph-based approaches we characterize 11 distinct structural haplotypes, several of which have not been previously described. Extending our analyses to a set of haplotype-resolved great-ape genomes, we characterize the structure of an independent inversion in chimpanzees which extends an additional 650kb, encompasses 5 additional genes, and is [~]2 million years younger than the human inversion. We further determine that gorillas exhibit an independent duplication of the KANSL1 gene which may predispose them to Koolen-de Vries syndrome causing microdeletions. Using short read sequencing data we characterize 17q21.31 haplotype diversity worldwide in [~]5174 individuals from 107 populations finding increased frequencies of KANSL1 duplication-containing haplotypes in both European and South Asian populations as well as 8 double recombination events between inverted and non-inverted haplotypes ranging in size from 20-180kb. Finally, using 626 ancient Eurasian human genomes we show the frequency of haplotypes containing KANSL1 duplications has increased [~]6-fold over the past 12 thousand years in Europe. Together, our results highlight the dynamics, complexity, and recurrent, independent evolution of a medically relevant locus across humans and great apes.

genomics↗

APOE4 genotype negates the benefits of 17β-estradiol on cerebrovascular endothelial and mitochondrial function

BackgroundPostmenopausal females who carry an APOE{varepsilon}4 allele are at higher risk of late-onset Alzheimers Disease compared to age-matched APOE{varepsilon}4 males. Estrogen deficiency predisposes females to an increased risk of vascular, cognitive, and metabolic impairments. While estrogen and APOE genotype are known to impact metabolic and mitochondrial function in the brain, their cerebrovascular effects are less understood. Thus, the purpose of this study was to determine the interaction between APOE genotype and estrogen on cerebrovascular endothelial and mitochondrial function. MethodsYoung female homozygous APOE{varepsilon}3 and APOE{varepsilon}4 mice (n=19-20/group; ~6 months old) fed a high-fat diet were ovariectomized (OVX), OVX and supplemented with 17{beta}-estradiol, or left intact. ResultsIn APOE{varepsilon}3 mice, OVX was associated with impaired posterior cerebral artery endothelium-dependent dilation, which was rescued by 17{beta}-estradiol. However, in APOE{varepsilon}4 mice, there was no effect of OVX or 17{beta}-estradiol on cerebral artery endothelial function. Carotid artery passive stiffness was greater with OVX and lower with 17{beta}-estradiol treatment in APOE{varepsilon}3 mice, but there was no impact of OVX or 17{beta}-estradiol in the APOE{varepsilon}4 mice. In cerebral arteries and arterioles, mitochondrial complexes I and I+II respiration were lower in APOE{varepsilon}4 mice compared with APOE{varepsilon}3 mice. 17{beta}-estradiol led to higher mitochondrial complex I respiration in APOE{varepsilon}3 but not APOE{varepsilon}4 mice. These functional differences were concomitant with group differences in mitochondrial DNA copy number, antioxidant enzymes, and pro-inflammatory factors. In contrast to other outcomes, we found that 17{beta}-estradiol treatment was associated with lower cerebral artery stiffness in APOE{varepsilon}4 but not APOE{varepsilon}3 mice. ConclusionsOverall, these results indicate that the APOE genotype modulates the impact of estrogen on the cerebral vasculature. We found that 17{beta}-estradiol enhances cerebrovascular endothelial and mitochondrial function in APOE{varepsilon}3 mice but not in APOE{varepsilon}4 mice. The results suggest that 17{beta}-estradiol supplementation has more cerebrovascular benefit for APOE{varepsilon}4 non-carriers. Novelty & SignificanceO_ST_ABSWhat is known?C_ST_ABSO_LIFemales have twice the risk of Alzheimers disease compared with males, and the APOE4 genetic variant is associated with a greater risk for Alzheimers disease compared with the APOE3 variant. C_LIO_LIThe risk for Alzheimers disease increases after menopause in females, suggesting that the loss of female sex hormones may play a role. C_LIO_LIThere are highly inconsistent results among past studies examining the interaction of APOE genotype and estrogens on cognitive function and other brain outcomes. C_LI What new information does this article contribute?Vascular outcomes were not measured in previous studies examining the interaction between APOE genotype and estrogens. As such, we aimed to determine the impact of APOE4 genotype on the cerebrovascular response to estradiol. We found that estradiol improved cerebral artery endothelial function and mitochondrial respiration in APOE3 mice following ovariectomy. In contrast, APOE4 mice were refractory to the beneficial effects of estradiol on cerebrovascular endothelial and mitochondrial function. The broader implication of this research is that APOE genotype may be a consideration when prescribing hormone replacement therapy to menopausal females due to the impact on vascular outcomes.

physiology↗

Tracing the drivers of range-wide bowhead whale genomic structure and diversity

Understanding how past environmental and anthropogenic factors shaped contemporary genetic patterns is essential for assessing the vulnerability of species in the face of ongoing climate change. The bowhead whale (Balaena mysticetus) - the only baleen whale found in the Arctic year-round - has a strong association with sea ice, long history of human exploitation, and a circumpolar distribution, making it a valuable model for investigating how these factors have shaped population structure in the marine Arctic. We analysed both nuclear and mitochondrial genomes from bowhead whale individuals sampled across the species circumpolar range, encompassing all four recognized management stocks. Our results reveal three not four genetically differentiated populations: the Sea of Okhotsk stock; the East Greenland-Svalbard-Barents Sea stock; and a combined population containing the Bering-Chukchi-Beaufort Seas and East Canada-West Greenland stocks. We utilised ecological niche modeling and bowhead whale telemetry data to model stock connectivity over the past 11,700 years, and identify past habitat connectivity as a key driver of current population structure. Despite centuries of intensive commercial whaling, the three bowhead whale populations exhibit little-to-no evidence of recent inbreeding and retain high genetic diversity relative to other mammalian species. The lowest genetic diversity, most inbreeding, and highest realised genetic load being in the Sea of Okhotsk population. Collectively, our findings shed light on the recent population history and dynamics of bowhead whales, and offer valuable baseline data on present-day genetic structure and diversity to support effective conservation and management strategies.

evolutionary biology↗

LRP10 promotes trafficking of progranulin and prosaposin to lysosomes

Mutations in LRP10, a low-density lipoprotein receptor family member, cause familial Parkinsons disease and dementia with Lewy bodies. However, its direct cellular functions remain largely undefined. Using a multidisciplinary approach, our new data shows that LRP10 is required for the efficient trafficking of progranulin and prosaposin to lysosomes. Loss of LRP10 resulted in aberrant Golgi accumulations of progranulin and prosaposin and their reduced abundance in lysosomes. Disease-linked LRP10 missense mutations failed to support this lysosomal trafficking. Moreover, LRP10 KO mice developed striking microgliosis marked by enlarged and hyper-ramified microglia, accompanied by progranulin accumulation in the Golgi. Our results define LRP10 as a positive regulator of progranulin and prosaposin lysosomal protein trafficking and microglia homeostasis and thus shed new light on how its dysfunction may drive neurodegeneration in Parkinsons Disease and dementia with Lewy bodies.

cell biology↗

Complete genomes of 152 root commensal bacteria from the model legume Lotus japonicus

Bacterial culture collections represent a valuable tool for mechanistic understanding of microbiome assemblies and are increasingly used to assemble tailored synthetic communities to characterize their microbe-microbe interactions and those with the environment. Given the size of these collections, short-read sequencing is primarily used to capture the encoded genetic information. Whilst sufficient for many microbiome studies, this approach is not amenable for understanding bacterial genome evolution or detailed genetic analyses at the entire genome level. Here we report the assembly of 152 full bacterial genomes from the Lj-SPHERE, the Lotus japonicus collection of root commensals. We performed long-read sequencing using Oxford Nanopore technology and used this together with pre-existing Illumina sequences to de novo assemble these into high quality genomes with improved contiguity and quality. These genomes now provide a solid platform for detailed, mechanistic understanding of microbiome assembly, dynamics and evolution in plants.

genomics↗

The STRIPAK complex is required for radial sorting and laminin receptor expression in Schwann cells

During peripheral nervous system development, Schwann cells undergo Rac1-dependent cytoskeletal reorganization as they insert cytoplasmic extensions into axon bundles to radially sort, ensheath, and myelinate individual axons. However, our understanding of the direct effectors targeted by Rac1 is limited. Here, we demonstrate that striatin-3 and MOB4 are novel Rac1 interactors. We show that, similar to Rac1-null Schwann cells, Schwann cell specific ablation of striatin-3 causes defects in lamellipodia formation. In addition, conditional Schwann cell knockout of multiple striatin proteins presents a severe delay in radial sorting. Finally, we demonstrate here that deletion of Rac1 or striatin-1/3 in Schwann cells causes defects in Hippo pathway regulation, phosphorylation of the Hippo pathway effectors YAP and TAZ, and expression of genes co-regulated by YAP and TAZ, such as extracellular matrix receptors. In summary, our results indicate that striatin-3 is a novel Rac1 interactor, show that striatin proteins are required for peripheral nervous system development, and reveal a role for Rac1 in regulation of the Hippo pathway in Schwann cells.

neuroscience↗

Extensive monolayer formation depends on a subpopulation of transplanted human iPSC-derived RPE cells

Loss of the retinal pigment epithelium (RPE) in the eye leads to photoreceptor dysfunction and death causing eventually vision loss. Cell replacement strategies using RPE cells derived in vitro from pluripotent stem cells (PSCs) are currently evaluated as a potential therapeutic strategy. Generation of polarized monolayers represents an essential prerequisite for proper RPE function, however, monolayer formation following transplantation of RPE cell suspensions has not been systematically assessed. Using the sodium iodate mouse model of acute RPE depletion, significant increase in monolayer formation capacity of passage (P) 1 vs. P2 human iPSC-derived RPE cells was observed three weeks after transplantation. Transplant-derived monolayers showed characteristic apicobasal polarity, RPE marker expression, phagocytosis function, and preservation of the host outer nuclear layer. The cell surface marker panel CD54+/PSA-NCAM- was identified to enrich for an RPE subpopulation with high potential for monolayer formation following transplantation. Results underline the importance of defining and isolating competent cell subpopulations for successful RPE transplantation.

neuroscience↗

A diploid chromosome-level genome of Eucalyptus regnans: unveiling haplotype variance in structure and genes within one of the world's tallest trees

BackgroundEucalyptus regnans (Mountain Ash) is an Australian native giant tree species which form forests that are among the highest known carbon-dense biomasses in the world. To enhance genomic studies in this ecologically important species, we assembled a high-quality, mostly telomere-to-telomere complete, chromosome-level, haplotype-resolved reference genome. We sampled a single tree, the Centurion, which is currently a contender for the worlds tallest flowering plant. ResultsUsing long-read sequencing data (PacBio HiFi, Oxford Nanopore ultra-long reads) and chromosome conformation capture data (Hi-C), we assembled the most contiguous and complete Eucalyptus reference genome to date. For each haplotype, we observed contig N50s exceeding 36 Mbp, scaffold N50s exceeding 43 Mbp, and genome BUSCO completeness exceeding 99%. The assembled genome revealed extensive structural variations between the two haplotypes, consisting mostly of insertions, deletions, duplications and translocations. Analysis of gene content revealed haplotype-specific genes, which were enriched in functional categories related to transcription, energy production and conservation. Additionally, many genes reside within structurally rearranged regions, particularly duplications, suggesting that haplotype-specific variation may contribute to environmental adaptation in the species. ConclusionsOur study provides a foundation for future research into E. regnans environmental adaptation, and the high-quality genome will be a powerful resource for conservation of carbon-dense giant tree forests.

genomics↗

Four centuries of commercial whaling eroded 11,000 years of population stability in bowhead whales

The bowhead whale, an Arctic endemic, was heavily overexploited during commercial whaling between the 16th-20th centuries1. Current climate warming, with Arctic amplification of average global temperatures, poses a new threat to the species2. Assessing the vulnerability of bowhead whales to near-future predictions of climate change remains challenging, due to lacking data on population dynamics prior to commercial whaling and responses to past climatic change. Here, we integrate palaeogenomics and stable isotope ({delta}13C and{delta} 15N) analysis of 201 bowhead whale fossils from the Atlantic Arctic with palaeoclimate and ecological modelling based on 823 radiocarbon dated fossils, 151 of which are new to this study. We find long-term resilience of bowhead whales to Holocene environmental perturbations, with no obvious changes in genetic diversity or population structure, despite large environmental shifts and centuries of whaling by Indigenous peoples prior to commercial harvests. Leveraging our empirical data, we simulated a time-series model to quantify population losses associated with commercial whaling. Our results indicate that commercial exploitation induced population subdivision and losses of genetic diversity that are yet to be fully realised; declines in genetic diversity will continue, even without future population size reductions, compromising the species resilience to near-future predictions of Arctic warming.

evolutionary biology↗

Elucidating the sustainability of 700 years of Inuvialuit beluga whale hunting in the Mackenzie River Delta, Northwest Territories, Canada

Beluga whales play a critical role in the subsistence economies and cultural heritage of Indigenous communities across the Arctic, yet the effects of Indigenous hunting on beluga whales remains unknown. Here, we integrate paleogenomics and stable{delta} 13C and{delta} 15N isotope analysis to investigate 700 years of beluga subsistence hunting in the Mackenzie Delta area of northwestern Canada. Genetic identification of the zooarchaeological remains, which based on radiocarbon dating span three time periods (1290-1440 CE; 1450-1650 CE; 1800-1870 CE), indicate shifts across time in the sex ratio of the harvested belugas. The equal number of females and males harvested in 1450-1650 CE versus more males harvested in the two other time periods may reflect changes in hunting practices or temporal shifts in beluga availability. We find temporal shifts and sex-based differences in {delta}13C of the harvested belugas across time, suggesting historical adaptability in the foraging ecology of the whales. Although we uncovered novel mitochondrial diversity in the Mackenzie Delta belugas, we found no changes in nuclear genomic diversity nor any substructuring across time. Our findings indicate the genomic stability and continuity of the Mackenzie Delta beluga population across the 700 years surveyed, indicating the impact of Inuvialuit subsistence harvests on the genetic diversity of contemporary beluga individuals has been negligible. Significance StatementSince colonizing the Mackenzie Delta in northwestern Canada [~]1200 CE, Inuvialuit have been heavily reliant on belugas for their livelihoods and cultural heritage. However, little is known of the impact of centuries of sustained Inuvialuit subsistence hunting on the beluga population inhabiting the Mackenzie Delta. Using palaeogenomic and stable isotope analysis of zooarchaeological remains, and comparing the findings with contemporary data, we investigate temporal changes in beluga diversity, structuring, and foraging ecology. We show Inuvialuit harvests had a negligible impact on the genetic diversity of contemporary Mackenzie belugas, and highlight the applicability of combining genomic sexing and isotope analysis of zooarchaeological remains for advancing our understanding of past hunting practices and faunal ecologies.

genomics↗