Biology subjects

Lorenzen, E.

Publications and source records attributed to Lorenzen, E..

14 recordsLinked to original sources

bioRxiv2026

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↗

bioRxiv2026

Evolutionary history and genomic vulnerability of the extinct giant deer Megaloceros giganteus

The extinct giant deer (Megaloceros giganteus) was one of the most striking megafaunal species of the Late Quaternary, distinguished by its enormous palmated antlers reaching up to 3.5 m across, the largest known among both living and extinct cervids. Despite its iconic status, little is known about its genomic history prior to extinction [~]8 thousand years ago (kya). We generated the first nuclear palaeogenomes for Megaloceros, represented by nine individuals from Germany ([~]40 kya) and Ireland ([~]11 kya), mapped to a new chromosome-level reference genome of the fallow deer (Dama dama). Phylogenomic analyses placed Megaloceros as sister to Dama (divergence [~]3.5 Ma) and revealed evidence of gene flow with ancestral Cervus lineages. Population analyses identified clear differentiation between German and Irish lineages, with higher genetic diversity in the German individuals. Two genes under strong positive selection, BNIPL and SLC10A7, are associated with apoptosis regulation and skeletal development/bone mineralisation, respectively, and may relate to the species large body and antler size. Demographic reconstructions indicate a long-term decline in effective population size, extremely low heterozygosity, little evidence of extensive runs of homozygosity, and an elevated burden of predicted deleterious alleles. Together, these results suggest that Megaloceros entered the terminal Pleistocene in a genomically fragile state, offering new insight into the biology and evolutionary legacy of one of the largest and most distinctive cervids that ever lived.

evolutionary biology↗

bioRxiv2025

Impact of tusk anomalies on the long-term foraging ecology of narwhals

Male narwhals are unique in having one long, spiralled tusk, while females of the species do not have a tusk. However, a small number of individuals develop tusk anomalies, including two-tusked males or females with a tusk. In this study, we combine genetic sexing and bone collagen stable isotope ({delta}13C and {delta}15N) analysis to evaluate whether these tooth anomalies impact foraging ecology. Our analysis of individuals collected in the waters around Greenland showed no systematic impacts; nine of ten two-tusked male narwhals, and all three one-tusked female narwhals were within the normal range of known isotopic diversity from the sampled geographic regions. Two specimens with other forms of unusual dentition both showed stable isotope values outside the range of narwhals, suggesting their diet was different. Our findings underscore how DNA data retrieved from museum specimens can elucidate biological questions of interest, such as the sex of anomalous individuals. They also show how stable isotope analysis can be used to assign individuals with unknown provenance to their geographic region of origin.

zoology↗

bioRxiv2024

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↗

bioRxiv2023

Late Pleistocene polar bear genomes reveal the timing of allele fixation in key genes associated with Arctic adaptation

The polar bear (Ursus maritimus) occupies a relatively narrow ecological niche, with many characteristics adapted for cold temperatures, movement across snow, ice and open water, and for consuming highly lipid-dense prey species. The divergence of polar bears from brown bears (Ursus arctos) and their adaptation to their Arctic lifestyle is a well-known example of rapid evolution. Previous research investigating whole genomes uncovered genomic regions containing an array of key genes highly differentiated between polar and brown bears, many of which were linked to the novel Arctic environment. Further research suggested fixed alleles in these genes arose from selection on both standing variation and de novo mutations in the evolution of polar bears. Here, we reevaluate these findings by incorporating more genomic data from previously unavailable polar and brown bear populations, and assess the timing of allele fixation by utilising the genomes of two Late Pleistocene polar bears (aged 130-100,000 years old and 100-70,000 years old). Contrary to previous results, we found no evidence for alleles fixed in all polar bears within these key genes arising from de novo mutation. Most alleles fixed in modern polar bears were also fixed in the Late Pleistocene bears, suggesting selection occurred prior to 70,000 years ago. However, some sites fixed in modern polar bears were not fixed in the Late Pleistocene bears, including at sites within APOB, LYST, and TTN. The functions of these three genes are associated with the cardiovascular functions, metabolism, and pigmentation, suggesting that selection may have acted on different loci at different times.

evolutionary biology↗

bioRxiv2023

Unpacking Unstructured Data: A Pilot Study on Extracting Insights from Neuropathological Reports of Parkinson's Disease Patients using Large Language Models

ObjectiveThe aim of this study was to make unstructured neuropathological data, located in the NeuroBioBank (NBB), follow FAIR principles, and investigate the potential of Large Language Models (LLMs) in wrangling unstructured neuropathological reports. By making the currently inconsistent and disparate data findable, our overarching goal was to enhance research output and speed. Materials and MethodsThe NBB catalog currently includes information from medical records, interview results, and neuropathological reports. These reports contain crucial information necessary for conducting in-depth analysis of NBB data but have multiple formats that vary across different NBB biorepositories and change over time. In this study we focused on a subset of 822 donors with Parkinsons disease (PD) from 7 NBB biorepositories. We developed a data model with combined Brain Region and Pathological Findings data at its core. This approach made it easier to build an extraction pipeline and was flexible enough to convert resulting data to Common Data Elements (CDEs), a standardized data collection tools used by the neuroscience community to improve consistency and facilitate data sharing across studies. ResultsThis pilot study demonstrated the potential of LLMs in structuring unstructured neuropathological reports of PD patients available in the NBB. The pipeline enabled successful extraction of detailed tissue-level (microscopic) and gross anatomical (macroscopic) observations, along with staging information from pathology reports, with extraction quality comparable to manual curation results. To our knowledge, this is the first attempt to automatically standardize neuropathological information at this scale. The collected data has the potential to serve as a valuable resource for PD researchers, facilitating integration with clinical information and genetic data (such as genome-wide genotyping and whole genome sequencing) available through the NBB, hereby enabling a more comprehensive understanding of the disease.

pathology↗

bioRxiv2023

The origins and diversification of Holarctic brown bear populations inferred from genomes of past and present populations

The brown bear (Ursus arctos) is one of the survivors of the Late Quaternary megafauna extinctions. However, despite being widely distributed across the Holarctic, brown bears have experienced extensive range reductions, and even extirpations in some geographic regions. Previous research efforts utilising genetic data have provided valuable insights into their evolutionary history. However, most studies have been limited to contemporary individuals or mitochondrial DNA, limiting insights into population processes that preceded the present. Here we present genomic data from two Late Pleistocene brown bears from Honshu, Japan, and eastern Siberia, and combine them with published contemporary and ancient genomes from across the Holarctic range of brown bears to investigate the evolutionary relationships among brown bear populations through time and space. By including genomic data from Late Pleistocene and Holocene individuals sampled outside the current distribution range we uncover diversity not present in the contemporary populations. Notably, although contemporary individuals display geographically structured populations most likely driven by isolation-by-distance, this pattern varies among the ancient samples across different regions. The inclusion of ancient brown bears in our analysis provides novel insights into the evolutionary history of brown bears and contributes to understanding the populations and diversity lost during the Late Quaternary.

evolutionary biology↗

bioRxiv2022

Itch receptor MRGPRX4 interacts with the receptor activity-modifying proteins (RAMPs)

Cholestatic itch is a severe and debilitating symptom in liver diseases with limited treatment options. The class A G protein-coupled receptor (GPCR) Mas-related GPCR subtype X4 (MRGPRX4) has been identified as a receptor for bile acids, which are potential cholestatic pruritogens. An increasing number of GPCRs have been shown to interact with receptor activity-modifying proteins (RAMPs), which can modulate different aspects of GPCR biology. Using a combination of multiplexed immunoassay and proximity ligation assay we show that MRGPRX4 interacts with RAMPs. The interaction of MRGPRX4 with RAMP2, but not RAMP1 or 3, causes attenuation of basal and agonist-dependent signaling, which correlates with a decrease of MRGPRX4 cell surface expression as measured using a quantitative NanoBRET pulse-chase assay. Finally, we use AlphaFold Multimer to predict the structure of the MRGPRX4-RAMP2 complex. The discovery that RAMP2 regulates MRGPRX4 may have direct implications for future drug development for cholestatic itch.

biochemistry↗

bioRxiv2022

Ancient dolphin genomes reveal rapid repeated adaptation to coastal waters

Parallel evolution provides among the strongest evidence of the role of natural selection in shaping adaptation to the local environment. Yet, the chronology, mode and tempo of the process of parallel evolution remains broadly debated and discussed in the field of evolutionary biology. In this study, we harness the temporal resolution of paleogenomics to understand the tempo and independence of parallel coastal ecotype adaptation in common bottlenose dolphins (Tursiops truncatus). For this, we generated whole genome resequencing data from subfossil dolphins (8,610-5,626 years BP) originating from around the formation time of new coastal habitat and compared them with data from contemporary populations. Genomic data revealed a shift in genetic affinity, with the oldest ancient sample being closer to the pelagic populations, while the younger samples had intermediate ancestry that showed greater affinity with the local contemporary coastal populations. We found coastal-associated genotypes in the genome of our highest coverage ancient sample, SP1060, providing rare evidence of rapid adaptation from standing genetic variation. Lastly, using admixture graph analyses, we found a reticulate evolutionary history between pelagic and coastal populations. Ancestral gene flow from coastal populations was the probable source of standing genetic variation present in the pelagic populations that enabled rapid adaptation to newly emerged coastal habitat. The genetic response to past climatic warming provides an understanding of how bottlenose dolphins will respond to ongoing directional climate change and shifting coastlines.

evolutionary biology↗

bioRxiv2022

Impact of Holocene environmental change on the evolutionary ecology of an Arctic top predator

The Arctic is among the most climatically sensitive environments on Earth, and the disappearance of multiyear sea-ice in the Arctic Ocean is predicted within decades. As apex predators, polar bears are sentinel species for addressing the impact of environmental variability on Arctic marine ecosystems. By integrating genomics, isotopic analysis, morphometrics, and ecological modelling, we investigate how Holocene environmental changes affected the evolutionary ecology of polar bears around Greenland. We show that throughout the last [~]11,000 years, Greenlandic polar bears have been heavily influenced by changes in sea-surface temperature (SST) and sea-ice cover. Most notable are major reductions in effective population size at the beginning of the Holocene and during the Holocene Thermal Maximum [~]6 kya, which coincide with increases in annual mean SST, reduction in sea-ice covers, declines in suitable habitat, and shifts in suitable habitat northwards. Furthermore, we show how individuals sampled from west and east Greenland are genetically, morphologically, and ecologically distinct. We find bears sampled in west Greenland to be larger, more genetically diverse and have diets dominated by ringed seals, whereas bears from east Greenland are smaller and less diverse with more varied diets, putatively driven by regional biotic differences. Taken together, we provide novel insights into the vulnerability of polar bears to environmental change, and how the Arctic marine ecosystem plays a vital role in shaping the evolutionary and ecological trajectories of its inhabitants. TeaserMultivariate investigations of the environments role in the evolutionary ecology of Greenlandic polar bears.

evolutionary biology↗

bioRxiv2022

Genomic insights into the evolutionary relationships and demographic history of kiwi

Kiwi are a unique and emblematic group of birds endemic to New Zealand. Deep-time evolutionary relationships among the five extant kiwi species have been difficult to resolve, in part due to the absence of pre-Quaternary fossils to inform speciation events among them. Here, we utilise single representative nuclear genomes of all extant kiwi species (great spotted kiwi, little spotted kiwi, Okarito brown kiwi, North Island brown kiwi, and southern brown kiwi) and investigate their evolutionary histories with phylogenomic, genetic diversity, and deep-time (past million years) demographic analyses. We uncover low levels of gene-tree phylogenetic discordance across the genomes, suggesting clear distinction between species. However, we also find indications of post-divergence gene flow, concordant with recent reports of interspecific hybrids. The four species with available reference assemblies show relatively low levels of genetic diversity, which we suggest reflects a combination of older environmental as well as more recent anthropogenic influence. In addition, we uncover similarities and differences in the demographic histories of the five kiwi species over the past million years, and suggest hypotheses regarding the impact of known past environmental events, such as volcanic eruptions and glacial periods, on the evolutionary history of the group.

evolutionary biology↗

bioRxiv2022

Sex and size matter: foraging ecology of offshore harbour porpoises in waters around Greenland

Individuals of different sex or age can vary in their resource use due to differences in behaviour, life history, energetic need, or size. Harbour porpoises are small cetaceans that rely on a constant prey supply to survive. Here, we use bone collagen carbon ({delta}13C) and nitrogen ({delta}15N) isotope compositions to elucidate sex and size differences in the foraging ecology of harbour porpoises from West Greenland. In this region, populations have a unique offshore, deep-water ecology. Female harbour porpoises are larger than males and we find that females have a higher trophic level than males, and {delta}15N positively correlates with size for females only. This indicates that size may matter in the ability of females to handle larger prey and/or dive deeper to catch higher trophic level prey. These results suggest that females, which also feed their calves, may be under different ecological constraints than males. We also analysed the harbour porpoise data with comparable stable isotope data from Greenland populations of belugas and narwhals. Consistent with their small body size, and a diet consisting primarily of capelin, we find that harbour porpoises have a lower trophic level than belugas and narwhals. Furthermore, harbour porpoises have the largest ecological niche of the three species, which is in accordance with tagging studies indicating they have a wide range in shelf and deep offshore waters of the sub-arctic and North Atlantic.

ecology↗

bioRxiv2019

Multiplexed Analysis of the Secretin-like GPCR-RAMP Interactome

Although receptor activity-modifying proteins (RAMPs) have been shown to modulate the functions of several different G protein-coupled receptors (GPCRs), potential direct interactions among the three known RAMPs and hundreds of GPCRs has never been investigated. We engineered three epitope-tagged RAMPs and 23 epitope-tagged GPCRs, focusing on the secretin-like family of GPCRs, and developed a suspension bead array (SBA) immunoassay designed to detect RAMP-GPCR complexes. We then used 64 antibodies raised against native RAMPs and GPCRs, along with four antibodies targeting the epitope tags, to multiplex the SBA assay to detect and measure all possible combinations of interaction among the 23 GPCRs and three RAMPs. The results of the SBA assay provide a complete interactome of secretin-like GPCRs with RAMPs. We demonstrate direct interaction of previously reported secretin-like GPCRs whose functions are modulated by RAMPs. We also discovered novel sets of GPCR-RAMP interacting pairs, and found additional secretin-like GPCRs, chemokine receptors and orphan receptors that interact with RAMPs. Using in situ roximity ligation assay, we verified a subset of these novel GPCR-RAMP interactions in cell membranes. In total, we found GPCR-RAMP interactions for the majority of the 23 GPCRs tested. Each GPCR interacted with either all three RAMPs or with RAMP2 and RAMP3, with the exception of one GPCR that interacted with just RAMP3. In summary, we describe an SBA strategy that will be useful to search for GPCR-RAMP interactions in cell lines and tissues, and conclude that GPCR-RAMP interactions are more common than previously appreciated.

biochemistry↗

bioRxiv2019

High-Affinity Binding of Chemokine Analogs that Display Ligand Bias at the HIV-1 Co-receptor CCR5

The chemokine receptor CCR5 is a drug target to prevent transmission of HIV/AIDS. We studied four analogs of the native chemokine RANTES (CCL5) that have anti-HIV potencies of around 25 pM, which is more than four orders-of-magnitude higher than that of RANTES itself. It has been hypothesized that the ultra-high potency of the analogs is due to their ability to bind populations of receptors not accessible to native chemokines. To test this hypothesis, we developed a homogeneous dual-color fluorescence cross-correlation spectroscopy (FCCS) assay for saturation and competition binding experiments. The FCCS assay has the advantage that it does not rely on competition with radioactively labeled native chemokines used in conventional assays. We prepared site-specifically labeled fluorescent analogs using native chemical ligation of synthetic peptides, followed by bioorthogonal fluorescent labeling. We engineered a mammalian cell expression construct to provide fluorescently labeled CCR5, which was purified using a tandem immunoaffinity and size-exclusion chromatography approach to obtain monomeric fluorescent CCR5 in detergent solution. We found subnanomolar binding affinities for the two analogs 5P12-RANTES and 5P14-RANTES, and about twenty-fold reduced affinities for PSC-RANTES and 6P4-RANTES. Using homologous and heterologous competition experiments with unlabeled chemokine analogs, we conclude that the analogs all bind at the same binding site; whereas, the native chemokines (RANTES and MIP1) fail to displace bound fluorescent analogs even at tens of micromolar concentrations. Our results can be rationalized with de novo structural models of the N-terminal tails of the synthetic chemokines that adopt a different binding mode as compared to the parent compound.

biophysics↗