Biology subjects

Carr, I. M.

Publications and source records attributed to Carr, I. M..

7 recordsLinked to original sources

bioRxiv2025

A genomic perspective on the origins, evolution and adaptation of Galapagos iguanas

Island taxa provide opportunities to explore the genomic basis of species diversification and trait evolution arising from adaptation to new environmental conditions and ecological niches. Here we generate the first genomic sequences for the four endemic Galapagos iguana species to reconstruct their evolutionary history and to identify genes which may contribute to their unique adaptations. We show that the marine (Amblyrhynchus) and land (Conolophus) lineages evolved in situ on now submerged islands, following a single colonisation event 9 - 12.4 million years ago. Genomic selection scans identified genes linked to traits potentially facilitating adaptation to the Galapagos environment, including specialised pigmentation phenotypes (e.g. ASIP, BCO2 and KITLG), DNA damage and UV irradiation inflammation responses (e.g. MAPK14 and BRAF), which may contribute to increased resilience to elevated UV exposure at equatorial latitudes. A shift from eumelanin (dark) to pheomelanin (yellow-orange) dominated colouration in Conolophus species may be attributable to fixed substitutions in the MC1R gene that influence protein structure and interactions, with the depigmented skin phenotype of the pink iguana additionally linked to positive selection in regulators of MITF activity, melanosome transport and dermal vasculature unique to that lineage. Further genes with signatures of positive selection in marine iguanas have putative functions including hypoxia response, that may be associated with their transition to underwater foraging (e.g. HBA, HMOX2, HIF), as well as their unique ability to repeatedly shrink and grow in body size through tissue and bone remodelling (e.g. AREG, BMP2, CPNE7). Genome-wide patterns of genetic diversity indicate recent inbreeding coincident with the timing of human settlement. Our study provides insights into the origins and diversification of the iguanas and the molecular basis of adaptation to life in the Galapagos, facilitating future conservation genomic management of threatened iguanid populations.

evolutionary biology↗

bioRxiv2024

Inferring species interactions from co-occurrence networks with environmental DNA metabarcoding data in a coastal marine food-web

Improved understanding of biotic interactions is necessary to accurately predict the vulnerability of ecosystems to climate change. Recently, co-occurrence networks built from environmental DNA (eDNA) metabarcoding data have been advocated as a means to explore interspecific interactions in ecological communities exposed to different human and environmental pressures. Co-occurrence networks have been widely used to characterise microbial communities, but it is unclear if they are effective for characterising eukaryotic ecosystems, or whether biotic interactions drive inferred co-occurrences. Here, we assess spatiotemporal variability in the structure and complexity of a North Sea coastal ecosystem inferred from co-occurrence networks and food webs using 60 eDNA samples covering vertebrates and other eukaryotes. We compare topological characteristics and identify potential keystone species, i.e., highly connected species, across spatial and temporal subsets, to evaluate variance in community composition and structure. We find consistent trends in topological characteristics across co-occurrence networks and food webs, despite trophic interactions forming a minority of significant co-occurrences. Known keystone species in food webs were not highly connected in co-occurrence networks. The lack of significant trophic interactions detected in co-occurrence networks may result from ecological complexities such as generalist predators having flexible interactions or behavioural partitioning, as well as methodological limitations such as the inability to distinguish age class with eDNA, or co-occurrences being driven by other interaction types or shared environmental requirements. Deriving biotic interactions with co-occurrence networks constructed from eDNA requires further validation in well-understood ecosystems, and improved reporting of methodological limitations, such as species detection uncertainties, which could influence inferred ecosystem complexity.

ecology↗

bioRxiv2023

Environmental DNA reveals fine scale spatial and temporal variation of prey species for marine mammals in a Scottish marine protected area

Marine mammal foraging grounds are popular focal points for marine protected area (MPA) implementation, but may be temporally dynamic, requiring continuous monitoring to infer prey availability and abundance. Marine mammal distributions are assumed to be driven by their prey in foraging areas, but limited understanding of prey distributions often prevents us from exploring how shifting prey availability impacts both seasonal and long-term marine mammal distributions. Environmental DNA (eDNA) metabarcoding could enhance understanding of marine mammal habitat use in relation to their prey through simultaneous monitoring of both. However, eDNA applications focused on marine mammals or predator-prey dynamics have been limited to date. In this study, we assess spatiotemporal changes in the availability and abundance of minke whale (Balaenoptera acutorostrata) prey species in a newly established MPA, employing eDNA metabarcoding. We recovered 105 molecular operational taxonomic units (OTUs) from marine vertebrates using two primer sets targeting 12S and 16S genes, along with 112 OTUs from a broader eukaryotic primer set targeting 18S rRNA. Overall, key forage fish prey species, sandeels and clupeids, were the most abundant teleost fishes detected, although their availability varied temporally and with distance from shore. We also found clear spatial partitioning between coastal bottlenose dolphins and the more pelagic minke whales and harbour porpoises, paralleling availability of their main prey species. Other species of conservation interest were also detected including the critically endangered European eel (Anguilla anguilla), blue fin tuna (Thunnus thynnus), and the invasive pink salmon (Oncorhynchus gorbuscha). This study demonstrates the application of eDNA to detect spatiotemporal trends in the occurrence and abundance of cetacean predators and their prey, furthering our understanding of fine-scale habitat use within MPAs. Future, long-term monitoring of predator-prey dynamics with eDNA could improve our ability to predict climate-induced shifts in foraging grounds and enhance rapid responses with appropriate management actions.

ecology↗

bioRxiv2023

Single Cell Track and Trace: live cell labelling and temporal transcriptomics via nanobiopsy.

Single-cell RNA sequencing has revolutionised our understanding of cellular heterogeneity, but whether using isolated cells or more recent spatial transcriptomics approaches, these methods require isolation and lysis of the cell under investigation. This provides a snapshot of the cell transcriptome from which dynamic trajectories, such as those that trigger cell state transitions, can only be inferred. Here, we present cellular nanobiopsy: a platform that enables simultaneous labelling and sampling from a single cell without killing it. The technique is based on scanning ion conductance microscopy (SICM) and uses a double-barrel nanopipette to inject a fluorescent dye and to extract femtolitre-volumes of cytosol. We used the nanobiopsy to longitudinally profile the transcriptome of single glioblastoma (GBM) brain tumour cells in vitro over 72hrs with and without standard treatment. Our results suggest that treatment either induces or selects for more transcriptionally stable cells. We envision the nanobiopsy will transform standard single-cell transcriptomics from a static analysis into a dynamic and temporal assay.

genomics↗

bioRxiv2021

Ferries and environmental DNA: underway sampling from commercial vessels provides new opportunities for systematic genetic surveys of marine biodiversity

Marine environmental DNA (eDNA) is an important tool for biodiversity research and monitoring but challenges remain in scaling surveys over large spatial areas, and increasing the frequency of sampling in remote locations at reasonable cost. Here we demonstrate the feasibility of sampling from commercial vessels (Mediterranean ferries) while underway, as a strategy to facilitate replicable, systematic marine eDNA surveys in locations that would normally be challenging and expensive for researchers to access. Sixteen eDNA samples were collected from 4 fixed sampling stations, and in response to 4 cetacean sightings, across three cruises undertaken along the 300 km ferry route between Livorno (Tuscany) and Golfo Aranci (Sardinia) in the Ligurian/Tyrrhenian Seas, June-July 2018. Using 12SrDNA and 16SrDNA metabarcoding markers, we recovered diverse marine vertebrate Molecular Operational Taxonomic Units (MOTUs) from teleost fish, elasmobranchs, and cetaceans. We detected sample heterogeneity consistent with previously known variation in species occurrences, including putative species spawning peaks associated with specific sea surface temperature ranges, and increased night time abundance of bathypelagic species known to undertake diel migrations through the water column. We suggest commercial vessel based marine eDNA sampling using the global shipping network has potential to facilitate broad-scale biodiversity monitoring in the worlds oceans.

molecular biology↗

bioRxiv2018

Plasmacytoid dendritic cells are functionally exhausted while non-haematopoietic sources of type I interferon dominate human autoimmunity

Autoimmune connective tissue diseases arise in a stepwise fashion from asymptomatic preclinical autoimmunity. Type I interferons (IFNs) have a crucial role in the progression to established autoimmune diseases such as systemic lupus erythematosus (SLE). However, their cellular source and regulation in disease initiation are unclear. The current paradigm suggests that plasmacytoid dendritic cells (pDCs) are activated in SLE contributing to excessive IFN production. Here, we show that in preclinical autoimmunity, established SLE, and primary Sjogrens Syndrome, pDCs are not effector cells, but rather have lost their capacity for TLR-mediated IFN- and TNF production and fail to induce T cell activation, independently of disease activity and blood IFN signature. In addition, pDCs present a transcriptional signature of cellular stress and senescence accompanied by increased telomere erosion. Instead, we demonstrate a marked enrichment of IFN signature in non-lesional skin in preclinical autoimmunity. In these individuals and SLE patients, type I IFNs were abundantly produced by keratinocytes in the absence of infiltrating leucocytes. These findings revise our understanding of the role of IFN in the initiation of human autoimmunity, with non-haematopoietic tissues perpetuating IFN responses, which in turn predict clinical disease. These data indicate potential therapeutic targets outside the conventional immune system for treatment and prevention.

immunology↗

bioRxiv2018

Interleukin-36 promotes systemic Type-I IFN responses in severe psoriasis.

Psoriasis is an immune-mediated skin disorder associated with severe systemic co-morbidities. Both chronic and acute forms of the disease are characterised by abnormal interleukin (IL)-36 signalling. While the mechanisms whereby IL-36 promotes cutaneous inflammation are well established, its systemic effects have not been investigated. To address this issue, we initially measured leukocyte gene expression in generalised pustular psoriasis, an acute disease variant caused by mutations of the IL-36 receptor antagonist. By undertaking whole-blood and neutrophil RNA-sequencing in affected individuals, we identified a Type-I IFN signature, which correlated with IL-36 signalling up-regulation. We then validated these observations in patients with chronic plaque psoriasis. Finally, we demonstrated that IL-36 acts directly on plasmacytoid dendritic cells, where it potentiates Toll-like Receptor (TLR)-9 activation and IFN production. This effect was mediated by the induction of PLSCR1, an endosomal TLR-9 transporter. These results define an IL-36/TLR-9/Type-I IFN axis that could be targeted for the treatment of psoriasis co-morbidities.

immunology↗