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Biology subjects

Taylor, R. S.

Publications and source records attributed to Taylor, R. S..

12 recordsLinked to original sources

A Single-Nucleus Transcriptomic Atlas Reveals Cell-Type-Specific Responses to OsHV-1 Infection in the Pacific Oyster

BackgroundThe Pacific oyster (Crassostrea/Magallana gigas) is increasingly recognised as a model marine invertebrate. Valued for both ecological and commercial importance, Pacific oysters are farmed widely, supporting global food security by providing a sustainable nutrient-rich source of protein. Despite the significant and recurring economic losses caused by Ostreid herpesvirus (OsHV-1) outbreaks, only a limited number of studies have examined host-pathogen interplay at single-cell resolution. The few available studies largely focus on circulating immune cells (haemocytes), thereby overlooking the complexity of host responses across different tissues and organs. ResultsWe present a detailed single-nucleus transcriptomic atlas of the whole Pacific oysters, including during OsHV-1 infection. A total of 18 distinct transcriptomic clusters were resolved, capturing major cell populations from the gill, mantle, hepatopancreas, adductor muscle, and haemocytes. Notably, three populations- gill ciliary cells, hepatopancreas cells, and an immune-enriched cluster 1- exhibited pronounced transcriptomic responses to OsHV-1 infection. Across the 6, 24, 72, and 96 hours post-infection (hpi) time course, viral transcripts were detected almost exclusively at 72 hpi, with enrichment primarily in adductor muscle cells and two immune cell populations- immature haemocytes, and hyalinocytes. ConclusionsOur findings suggest potential entry portals and tissue-specific replication sites for the OsHV-1 virus in Pacific oysters. This atlas resource provides a high-resolution cellular framework for understanding host-virus interactions and establishes a foundation for future investigations into herpesvirus pathogenesis in marine invertebrates.

genomics↗

Transposable element-mediated co-option drives the evolution of the miRNA regulatory system in Oryza AA-genome species

MicroRNAs (miRNAs) are key post-transcriptional regulators in plants, yet the evolutionary dynamics of the entire miRNA-mediated regulatory system remain poorly understood. We performed small RNA sequencing and comparative genomics analyses across all eight AA-genome species of Oryza within a well-resolved phylogenetic framework. We found that miRNA gene (MIRNA) families evolve with low birth-death rates, while individual paralogous MIRNAs turn over rapidly. We identified a novel mechanism in which transposable element (TE) insertions de novo generates functional miRNA target sites. miRNA target genes are characterized by distinct evolutionary signatures, including greater sequence length, lower GC content, moderately highly expression, reduced expression variability, and higher evolutionary conservation, which is consistent with their role as a conserved kernel regulatory subsystem. In contrast, the majority of recently evolved target genes that have acquired their miRNA binding sites through TE insertions tend to exhibit the opposite set of features. Furthermore, we uncovered co-evolutionary signatures between duplicated MIRNAs and their target genes, as well as between MIRNAs and phased siRNAs (phasiRNAs). Taken together, our study reveals multi-level evolutionary dynamics driven by TEs that rapidly generate new regulatory circuit and proposes a generalizable TE-MIRNA co-option model for regulatory network expansion in plants.

genomics↗

Embracing the power of genomics to inform evolutionary significant units

Appropriate identification of evolutionary significant units (ESUs) is essential for effective conservation planning. Genomic data has emerged as a key tool to inform ESU decisions due to the increased information resolution, yet it remains unclear how genomic data are being used in practice to identify the number of ESUs. To address this, we conducted a systematic literature review and found that genomic data are increasingly being used to suggest numbers of ESUs globally across plant and animal taxa. However, our review revealed inconsistencies in how ESUs are defined, with many studies not providing a definition at all. We also found inconsistencies in the methods used to analyze genomic data, highlighting the need for greater standardization to ensure studies adequately address all components of an ESUs. Adaptive loci, a key advantage of genomic data, need to be interpreted with caution and simply identifying these loci may lead to inflated ESU estimates. Overall, we found that 68% of studies suggested an increase in the number of ESUs, and that the amount of gene flow detected did not appear to influence this conclusion. We outline how genomic data can be used to assess the two key components of ESUs and provide recommendations for future studies aiming to identify ESUs with genomic data.

genomics↗

Virus-inclusive single-nucleus RNA sequencing reveals two distinct endothelial response patterns in infectious salmon anaemia.

Viral replication in endothelial cells is a hallmark of many viral diseases in humans and other animals, underscoring the importance of understanding cellular mechanisms that restrict viral replication and the associated consequences for vascular health. Pathogenic variants of infectious salmon anaemia virus (ISAV, Isavirus salaris) target endothelial cells of Atlantic salmon (Salmo salar L.), causing severe systemic disease and major losses during outbreaks in aquaculture. To better understand the endothelial response to ISAV, we used single nucleus RNA-sequencing at pre-clinical (12 days post infection, dpi) and clinical (16 dpi) stages of infection. Our approach enables an assessment of transcriptomic responses for different endothelial subpopulations at unprecedented resolution. ISAV RNA was predominantly detected in endothelial cells, which, along with mononuclear phagocytes, showed the highest number of differentially regulated genes at both time points. At 12 dpi, differentially expressed genes in endothelial cells were enriched for pathways related to NOD-like receptor signaling, antiviral responses, and regulation of programmed cell death. By 16 dpi, we observed a shift toward enrichment of pathways associated with cellular senescence, apelin signaling, and insulin signaling. We identified two distinct infection-related states at both time points: a virus-permissive state characterized by upregulation of genes involved in protein synthesis, small GTPase signaling, and MAPK activity, and a bystander phenotype marked by activation of antiviral responses, immune signaling, and translational regulation. This study is the first to capture the individual cell type responses to ISAV infection, and to characterize the in vivo endothelial response to active viral replication at single-cell resolution in any species.

immunology↗

Characterization of bacteria colonizing the mucosal layer of the gastrointestinal tract of Atlantic salmon farmed in a warm water region

Atlantic salmon (Salmo salar) farmed in seawater in Tasmania (lutruwita) can experience temperatures close to their thermotolerance limit during summer. Gut microbiome data from eight successive annual surveys and a specific survey of GI tract mucosa and digesta bacterial cross-sectional distributions indicated members of the genus Aliivibrio, Vibrio, and an unclassified Mycoplasmoidaceae are the main colonizers of the gut mucosal layer in Tasmanian farmed salmon. Peak abundance levels are reached after 7-8 months, corresponding to the late summer, following the transfer of hatchery smolt to seawater farms. Salmon Aliivibrio isolates comprise three novel non-bioluminescent species distinct from species found in the northern hemisphere growing regions. Along with other Aliivibrio species these species share many genes required for host colonization and biofilm formation and also include species and strain-level dependent features. Two of the novel Aliivibrio species surprisingly possessed genes for cytolethal distending toxin while the more predominant species lacked any known virulence genes. The overall observations suggest a small number of species actively colonize the mucosal layer of Atlantic salmon farmed in Tasmania and that this process is strongly influenced by the environmental temperature.

microbiology↗

Continent-wide phylogenomic framework reveals introgression as a driver of intra-specific diversity and enriched molecular pathways in caribou

High intra-specific genetic diversity is associated with adaptive potential which is key for resilience to global change. However, high variation may also support deleterious alleles through genetic load, unless purged, thereby increasing the risk of inbreeding depression if population sizes decrease rapidly. Purging of deleterious variation has now been demonstrated in some threatened species. However, less is known about the costs of population declines and inbreeding in species with large population sizes and high genetic diversity even though this encompasses many species globally that have or are expected to undergo rapid population declines. Caribou is a species of ecological and cultural significance in North America with a continental-wide distribution supporting extensive phenotypic variation, but with some populations undergoing significant declines resulting in their at-risk status in Canada. We assessed intra-specific genetic variation, adaptive divergence, inbreeding, and genetic load across populations with different demographic histories using an annotated chromosome-scale reference genome and 66 whole genome sequences. We found high genetic diversity and nine phylogenomic lineages across the continent with adaptive diversification of genes, but also high genetic load among lineages. We also found highly divergent levels of inbreeding across individuals including the loss of alleles by drift (genetic erosion) but not purging, likely due to rapid population declines not allowing time for purging of deleterious alleles. As a result, further inbreeding may need to be mitigated through conservation efforts. Our results highlight the double-edged sword of genetic diversity that may be representative of other species-at-risk affected by anthropogenic activities.

genomics↗

Single cell transcriptomics of Atlantic salmon (Salmo salar L.) liver reveals cellular heterogeneity and immunological responses to challenge by Aeromonas salmonicida

The liver is a multitasking organ with essential functions for vertebrate health spanning metabolism and immunity. In contrast to mammals, our understanding of liver cellular heterogeneity and its role in regulating immunological status remains poorly defined in fishes. Addressing this knowledge gap, we generated a transcriptomic atlas of 47,432 nuclei isolated from the liver of Atlantic salmon (Salmo salar L.) contrasting control fish with those challenged with a pathogenic strain of Aeromonas salmonicida, a problematic bacterial pathogen in global aquaculture. We identified the major liver cell types and their sub-populations, revealing poor conservation of many hepatic cell marker genes utilized in mammals, while identifying novel heterogeneity within the hepatocyte, lymphoid, and myeloid lineages. This included polyploid hepatocytes, multiple T cell populations including {gamma}{delta} T cells, and candidate populations of monocytes/macrophages/dendritic cells. A dominant hepatocyte population radically remodeled its transcriptome following infection to activate the acute phase response and other defense functions, while repressing routine functions such as metabolism. These defense-specialized hepatocytes showed strong activation of genes controlling protein synthesis and secretion, presumably to support the release of acute phase proteins into circulation. The infection response further involved up-regulation of numerous genes in an immune-cell specific manner, reflecting functions in pathogen recognition and killing, antigen presentation, phagocytosis, regulation of inflammation, B cell differentiation and T cell activation. Overall, this study greatly enhances our understanding of the multifaceted role played by liver cells in immune defense and metabolic remodeling following infection and provides many novel cell-specific marker genes to empower future studies of this organ in fishes.

immunology↗

A de novo genome assembly and annotation of the southern flying squirrel (Glaucomys volans)

Northern (Glaucomys sabrinus) and southern (Glaucomys volans) flying squirrels are widespread species distributed across much of North America. Northern flying squirrels are common inhabitants of the boreal forest, also occurring in coniferous forest remnants farther south, whereas the southern flying squirrel range is centered in eastern temperate woodlands. These two flying squirrel species exhibit a hybrid zone across a latitudinal gradient in an area of recent secondary contact. Glaucomys hybrid offspring are viable and can successfully backcross with either parental species, however, the fitness implications of such events are currently unknown. Some populations of G. sabrinus are endangered, and thus, interspecific hybridization is a key conservation concern in flying squirrels. We sequenced and assembled a de novo long-read genome from a G. volans individual sampled in southern Ontario, Canada, while four short-read genomes (2 G. sabrinus and 2 G. volans, all from Ontario) were re-sequenced on Illumina platforms. The final genome assembly consisted of approximately 2.40Gb with a scaffold N50 of 455.26Kb. Benchmarking Universal Single-Copy Orthologs reconstructed 3,742 (91.2%) complete mammalian genes and genome annotation using RNA-seq identified the locations of 19,124 protein-coding genes. The four short-read individuals were aligned to our reference genome to investigate the demographic history of the two species. A Principal Component Analysis clearly separated re-sequenced individuals, while inferring population size history using the Pairwise Sequentially Markovian Coalescent model noted an approximate species split one million years ago, and a single, possibly recently introgressed individual.

genomics↗

Genomic islands of heterozygosity maintained across caribou populations despite inbreeding

Small, isolated populations are prone to inbreeding, increasing the proportion of homozygous sites across the genome that can be quantified as runs of homozygosity (ROH). Caribou (Rangifer tarandus) are declining across their range in Canada; thus, understanding the effects of inbreeding on genetic potential is pertinent for conserving small, isolated populations. We quantified ROH in high-coverage whole genomes of boreal caribou from small, isolated populations in southern Ontario, Canada, in comparison to caribou from the continuous range of Ontario, other caribou ecotypes in Canada, and western Greenland. Sampled populations presented divergent evolutionary histories, differing population sizes, and extents of isolation. We conducted BLAST searches across regions of elevated heterozygosity to identify genes that have maintained variation despite inbreeding. We found caribou from recently isolated populations in Ontario had a large proportion of their genome in long ROH. We observed even larger proportions but shorter ROH in western Greenland, indicating that inbreeding has occurred over a longer period in comparison to other populations. We observed the least inbreeding in barren-ground and eastern migratory caribou, which occur in larger population sizes than boreal caribou. Despite vastly different inbreeding extents, we found regions of high heterozygosity maintained across all populations. Within these islands of heterozygosity, we identified genes associated with immunity, signaling regulation, nucleotide binding, toxin elimination, and feeding behaviour regulation. In this study, we confirm inbreeding in isolated populations of a species at risk, but also uncover high variation in some genes maintained across divergent populations despite inbreeding, suggesting strong balancing selection.

genomics↗

Major diversification of caribou shaped by glacial cycles before the Last Glacial Maximum

Pleistocene glacial cycles influenced the diversification of high-latitude wildlife species through recurrent periods of range contraction, isolation, divergence, and expansion from refugia and subsequent admixture of refugial populations. For many taxa, research has focused on genetic patterns since the Last Glacial Maximum (LGM), however glacial cycles before the LGM likely impacted genomic variation which may influence contemporary genetic patterns. We investigate diversification and the introgressive history of caribou (Rangifer tarandus) in western Canada using 33 high-coverage whole genomes coupled with larger-scale mitochondrial data. Contrary to the well-established paradigm that caribou ecotypes and contemporary genetic diversity arose from two major lineages in separate refugia during the LGM, a Beringian-Eurasian (BEL) and a North American (NAL) lineage, we found that the major diversifications of caribou occurred much earlier at around 110 kya, the start of the last glacial period. Additionally, we found effective population sizes of some caribou reaching ~700,000 to 1,000,000 individuals, one of the highest recorded historical effective population sizes for any mammal species thus far. Mitochondrial analyses dated introgression events prior to the LGM dating to 20-30 kya and even more ancient at 60 kya, coinciding with colder periods with extensive ice coverage, further demonstrating the importance of glacial cycles and events prior to the LGM in shaping demographic history. Reconstructing the origins and differential introgressive history has implications for predictions on species responses under climate change. Our results highlight the need to investigate pre-LGM demographic patterns to fully reconstruct the origin of species diversity, especially for high-latitude species.

evolutionary biology↗

Cytonuclear discordance in the crowned-sparrows, Zonotrichia atricapilla and Zonotrichia leucophrys: a mitochondrial selective sweep?

The golden-crowned (Zonotrichia atricapilla) and white-crowned (Z. leucophrys) sparrows have been presented as a compelling case for rapid speciation. They display divergence in song and plumage with overlap in their breeding ranges implying reproductive isolation, but have almost identical mitochondrial genomes. Previous research proposed hybridization and subsequent mitochondrial introgression as an alternate explanation, but lacked robust nuclear gene trees to distinguish between introgression and incomplete lineage sorting. We test for signatures of these processes between Z. atricapilla and Z. leucophrys, and investigate the relationships among Z. leucophrys subspecies, using mitochondrial sequencing and a reduced representation nuclear genomic dataset. Contrary to the paraphyly evident in mitochondrial gene trees, we confirmed the reciprocal monophyly of Z. atricapilla and Z. leucophrys using large panels of single nucleotide polymorphism (SNPs). The pattern of cytonuclear discordance is consistent with limited, historical hybridization and mitochondrial introgression, rather than a recent origin and incomplete lineage sorting between recent sister species. We found evidence of nuclear phylogeographic structure within Z. leucophrys with two distinct clades. Altogether, our results support the true species status of Z. atricapilla and Z. leucophrys, and indicate deeper divergences between the two species than inferred using mitochondrial markers. Our results demonstrate the limitations of relying solely on mitochondrial DNA for taxonomy, and raise questions about the possibility of selection on the mitochondrial genome during temperature oscillations (e.g. during the Pleistocene). Historical mitochondrial introgression facilitated by past environmental changes could cause erroneous dating of lineage splitting in other taxa when based on mitochondrial DNA alone.

evolutionary biology↗

Resolving the fibrotic niche of human liver cirrhosis using single-cell transcriptomics

Currently there are no effective antifibrotic therapies for liver cirrhosis, a major killer worldwide. To obtain a cellular resolution of directly-relevant pathogenesis and to inform therapeutic design, we profile the transcriptomes of over 100,000 primary human single cells, yielding molecular definitions for the major non-parenchymal cell types present in healthy and cirrhotic human liver. We uncover a novel scar-associated TREM2+CD9+ macrophage subpopulation with a fibrogenic phenotype, that has a distinct differentiation trajectory from circulating monocytes. In the endothelial compartment, we show that newly-defined ACKR1+ and PLVAP+ endothelial cells expand in cirrhosis and are topographically located in the fibrotic septae. Multi-lineage ligand-receptor modelling of specific interactions between the novel scar-associated macrophages, endothelial cells and collagen-producing myofibroblasts in the fibrotic niche, reveals intra-scar activity of several major pathways which promote hepatic fibrosis. Our work dissects unanticipated aspects of the cellular and molecular basis of human organ fibrosis at a single-cell level, and provides the conceptual framework required to discover rational therapeutic targets in liver cirrhosis.

immunology↗