Biology subjects

van Dorp, L.

Publications and source records attributed to van Dorp, L..

At least 19 recordsLinked to original sources

bioRxiv2026

The Genomic Landscape of Post-Black Death Epidemics in Northern Europe and the Caucasus

One of the most devastating events in human history, the Black Death (c.1347-1353), marked the beginning of the Second Plague Pandemic. After initially receding, plague returned in intermittent outbreaks throughout Europe, beginning with the pestis secunda. Despite its significance, the post-Black Death epidemiology of Yersinia pestis remains poorly understood. Here, we report 23 new Y. pestis genomes recovered from Second Plague Pandemic contexts across Scandinavia, the Netherlands, Iceland, and Armenia, spanning approximately 270 years. Applying a reproducible mutation-filtering pipeline to assess genetic diversity, we report both Black Death and post-Black Death lineages and document multiple waves of plague at individual cemetery sites. We identify four pestis secunda genomes, including three from Armenia, supporting the eastward dissemination of this lineage prior to its disappearance from Europe. We also resolve a previously under-characterised Branch 1A sub-lineage of Y. pestis and provide the first genomic evidence of plague in Iceland, resolving longstanding uncertainty over its presence on the island. Finally, by calling variants against a reconstructed ancestral reference, we identify clade-defining mutations, including nonsynonymous changes in metabolic and biofilm-related genes with predicted structural effects that may have contributed to shaping the epidemiological dynamics of the Second Plague Pandemic.

genetics↗

bioRxiv2026

Mothers face immediate, but family-size dependent, costs of sons in preindustrial Finland

The expensive son hypothesis posits that mothers incur higher fitness costs when caring for sons versus daughters in species with male-biased size dimorphism. Evidence for maternal survival costs of sons in humans is limited to shortened overall lifespans; whether having more sons reduces short-term survival during reproductive years is unknown. Here, we utilised life-history data from 5,456 mothers from preindustrial Finland to examine whether mothers with more sons had reduced survival within one year of their last birth. While mothers with few children but more sons showed no differences in survival, at higher family sizes, mothers with more sons had increasingly lower survival. These differences peaked at [~]0.4% lower survival per son among mothers with five children, suggesting accumulated physiological costs of sons. These differences then declined and reversed among mothers with more children, potentially due to selective disappearance of frailer mothers. Our results suggest that studies focusing on post-menopausal mothers may bias estimates of the fitness costs of sons and reproductive costs more broadly. We recommend future research further examines the overlooked short-term fitness costs of sons during reproductive years, which is vital for understanding how life-history trade-offs, sexual dimorphism, and their interaction have shaped human evolution.

evolutionary biology↗

bioRxiv2025

Characterising the microbial and antimicrobial resistance signatures of hospital-acquired pneumonia using nanopore metagenomic sequencing

Hospital-acquired pneumonia (HAP) is a significant burden in nosocomial settings, yet its microbial underpinnings remain poorly understood. Here, we leverage shotgun nanopore sequencing to characterise the respiratory microbiomes of 250 HAP patients in a UK multi-site cohort, validating these using paired PCR and culture assays. Sequencing identified the dominant microbes implicated in HAP, including detection of probable pathogens in 49 PCR- and culture-negative cases. We found a high prevalence of fungi in 81/239 (34%) in HAP patients, of whom 26/81 (32%) were PCR/culture-negative, suggesting that fungi may represent an under-investigated component of HAP, whether as colonists or pathogens. Although HAP is clinically sub-categorised based on the use and duration of ventilation before disease onset, we found that the microbial profiles of these sub-groups were indistinguishable. We also found a concerningly high proportion of multi-drug-resistant microbes in HAP patients, with 21% of assembled bacterial genomes harbouring acquired antimicrobial resistance (AMR) genes that confer resistance to at least three classes of antimicrobials. This included high AMR gene carriage associated to Staphylococcus epidermidis, which may be an important reservoir of AMR, though typically viewed as a commensal. Our work provides extensive metagenomic characterisation of HAP, underscores the value of metagenomics in describing its complex aetiology, and further prompts its potential role for pathogen detection, resistance profiling and treatment.

microbiology↗

bioRxiv2025

Climate associated natural selection in the human mitochondrial genome

Mitochondria are essential for cellular energy production and biosynthesis, thermogenesis, and cell signalling, and thus help coordinate physiological responses to changing environments. Humans (Homo sapiens) have adapted to cope with a wide range of climatic conditions, however the role of the mitochondrial genome (mtDNA) in mediating this process remains poorly understood. Here we curated a dataset of 23,790 publicly available full human mitochondrial genomes, an approximate 40-fold increase on earlier studies, paired with modern climate and reconstructed paleoclimate variables. Using a Generalised Linear Model approach, we identify 18 independent candidate variants significantly associated with climatic conditions, suggesting local adaptation in human mitochondrial genomes. Candidate variants are distributed across multiple loci in regulatory, tRNA, rRNA and protein-coding regions - including prominently in ND2 and ND4 complex I subunits. Specific variants are predicted to impact mtDNA transcription, ribosome or protein structure, and multiple have been associated with disease pathologies. We further show that candidate variant genotype distributions are each best modelled by different paleo-bioclimatic variables, consistent with environmental stressors linked to our measured variables exerting subtly distinct selective effects. These stressors may reflect dietary changes or different thermogenic demands at lower temperatures. Our results provide genetic evidence to support the accumulating body of work from functional studies that mitochondria can modulate adaptation to diverse environments. This work underscores the importance of mtDNA in evolutionary biology and its relevance for understanding both disease and physiological variation in global populations.

evolutionary biology↗

bioRxiv2024

Intrahost dynamics, together with genetic and phenotypic effects predict the success of viral mutations

Predicting the fitness of mutations in the evolution of pathogens is a long-standing and important, yet largely unsolved problem. In this study, we used SARS-CoV-2 as a model system to explore whether the intrahost diversity of viral infections could provide clues on the relative fitness of single amino acid variants (SAVs). To do so, we analysed [~]15 million complete genomes and nearly [~]8000 sequencing libraries generated from SARS-CoV-2 infections, which were collected at various timepoints during the COVID-19 pandemic. Across timepoints, we found that many of the SAVs that went on to reach high frequency could be detected in the intrahost diversity of samples collected at a median of 3-22 months prior. Additionally, we found that genetic linkage patterns observed at the interhost level can also be observed in the intrahost diversity of infections. Application of machine learning models allowed us to learn highly generalisable intrahost, physiochemical and phenotypic patterns to forecast the future fitness of intrahost SAVs (r2=0.48-0.63). Most of these models performed significantly better when considering genetic linkage between mutations (r2=0.53-0.67), pointing to epistasis being an important determinant in the evolution of SARS-CoV-2. Overall, our results highlight the predictive power of intrahost diversity data, and document the evolutionary forces shaping the fitness of mutations. Such insights offer potential to forecast the emergence of future variants and ultimately inform the design of vaccine targets.

genomics↗

bioRxiv2024

Ancient Borrelia genomes document the evolutionary history of louse-borne relapsing fever

Several disease-causing bacteria have transitioned from tick-borne to louse-borne transmission, a process associated with increased virulence and genome reduction. However, the historical time frame and speed of such evolutionary transitions have not been documented with ancient genomes. Here, we discover four ancient cases of Borrelia recurrentis, the causative agent of louse-borne relapsing fever, in Britain between [~]600 and 2,300 years ago, and sequence whole genomes up to 29-fold coverage. We estimate a recent divergence from the closest tick-borne ancestor, likely within the last [~]8,000 years. We reconstruct a chronology of gene losses and acquisitions using the pan-genome of related species, and show that almost all of the reductive evolution observed in B. recurrentis had occurred by [~]2,000 years ago, and was thus a rapid process after divergence. Our observations provide a new understanding of the origins of B. recurrentis and document complex reductive evolution in a specialist vector-borne pathogen.

evolutionary biology↗

bioRxiv2024

Early evolution of the BA.2.86 variant sheds light on the origins of highly divergent SARS-CoV-2 lineages

Since the emergence of SARS-CoV-2 in late 2019, highly divergent variants with novel constellations of mutations have periodically emerged to displace previously co-circulating virus lineages. The evolutionary mechanisms behind this process remain unclear, but the prevailing hypothesis supports emergence through single events followed by a rapid accumulation of mutations in individual long-term infections. In July 2023, the Omicron-descending BA.2.86 Variant of Interest (VOI) emerged to outcompete other virus lineages, with descending sublineages still dominating as of December 2024. We use BA.2.86 as a case study to test the hypothesis that highly divergent variants emerge during a single chronic infection. By applying a comprehensive suite of evolutionary analyses to independent high-resolution datasets, we identify a cluster of approximately 100 BA.2 genomes that fall directly ancestral and shorten the branch leading to BA.2.86, carrying some BA.2.86-specific lineage defining mutations. These genomes, sampled from multiple countries and at different timepoints, share a single ancestor dating back to December 2021. Additionally, we detect over 2600 earlier BA.2, BA.2.75, and XBB.1.5 genomes with multiple mutations later associated with BA.2.86. These genomes represent a standing genetic variation that likely facilitated a gradual evolution in the direct ancestry of this variant. We further uncover a complex evolutionary process involving recombination between the BA.2.75 and XBB.1.5 parental lineages. Together, our results challenge the notion of a single emergence event, and instead support a more complex scenario, with BA.2.86 likely having evolved over multiple transmission chains.

evolutionary biology↗

bioRxiv2024

2500 Years of Human Betaherpesvirus 6A and 6B Evolution Revealed by Ancient DNA

Human betaherpesviruses 6A and 6B are double-stranded DNA viruses, specialised in infecting humans and are best known as the main causative pathogens of the common childhood infection "sixth disease". Despite only being discovered in the 1980s, these viruses are speculated to have a much longer and more complex history within the human population than available modern data make clear. The viruses are carried by large fractions of the human population and can integrate into the human genome, leading to a wide range of clinical manifestations of varied severity. Here, we present the first nine full and two partial ancient genomes of HHV-6A and 6B, dating as far back as the Italian Iron Age (ca. 1100-600 BCE). We demonstrate that large fractions of the current HHV-6 diversity were already well established in the human population by the 14th century CE. Our data suggests that HHV-6B integrated into the human genome at the latest before the 1st-6th century CE, with two integrated clades being populated by ancient DNA genomes in our phylogeny, which further supports that they originated from likely much older ancient founder events. Additionally, we show that all known inherited chromosomally integrated (ici-)HHV-6A clades were already represented in European historical populations, confirming that ici-HHV-6A no longer integrates into the human germline within populations of European ancestry and likely endogenized in early human history. Finally, our results demonstrate the unique suitability of archaeological remains and ancient DNA for the study of the evolution of integrated viruses in human populations.

evolutionary biology↗

bioRxiv2023

Crossing host boundaries: the evolutionary drivers and correlates of viral host jumps

Most emerging and re-emerging infectious diseases stem from viruses that naturally circulate in non-human vertebrates. When these viruses cross over into humans, they can cause disease outbreaks and epidemics. While zoonotic host jumps have been extensively studied from an ecological perspective, little attention has gone into characterising the evolutionary drivers and correlates underlying these events. To address this gap, we harnessed the entirety of publicly available viral genomic data, employing a comprehensive suite of network and phylogenetic analyses to investigate the evolutionary mechanisms underpinning recent viral host jumps. Notably, we challenge conventional assumptions about the directionality of host jumps, demonstrating that humans are as much a source as a sink for viral spillover events, insofar we infer more viral host jumps from humans to other animals, than from animals to humans. Moreover, we demonstrate heightened evolution in viral lineages that involve putative host jumps. We further observe that the extent of adaptation associated to a host jump is lower for viruses with broad host ranges. Finally, we show that the genomic targets of natural selection associated to host jumps vary across different viral families with either structural or auxiliary genes being the prime targets of selection. Collectively, our results illuminate some of the evolutionary drivers underlying viral host jumps that may contribute to mitigating viral threats across species boundaries.

genomics↗

bioRxiv2023

The inter-continental population dynamics of Neisseria gonorrhoeae

Neisseria gonorrhoeae is a globally distributed sexually transmitted bacterial pathogen. Recent studies have revealed that its evolution has been shaped by antibiotic use, while molecular surveillance efforts have demonstrated large changes in lineage composition over relatively short time-spans. However, the global population dynamics of N. gonorrhoeae remain unsatisfyingly characterized. To reconstruct recent large-scale population dynamics, we generated a dated phylogeny from 9,732 N. gonorrhoeae genomes and found the effective population size of the species to have expanded gradually over the past two centuries. While the effective population size of clades with reduced susceptibility to extended-spectrum cephalosporins started declining around 2010, a major clade containing a mosaic mtr operon associated with cephalosporin susceptibility and decreased azithromycin did not display any reduction in population size. Using ancestral trait reconstruction analyses, we delineated transmission lineages, defined as groups of sequences in which all the samples can be traced back to the same import event to a given location. Import, export and local transmission dynamics across two densely sampled locations (Norway and Victoria, Australia) were investigated in detail. Norway exhibited substantially higher rates of strain import and export compared to Victoria, where incidence was to a larger extent fuelled by locally transmitted lineages. Taken together, our work highlights the power of large-scale phylogenomic analyses to uncover the complex dynamics of lineage transmission in N. gonorrhoeae.

microbiology↗

bioRxiv2023

Surveillance of 16 UK native bat species through conservationist networks uncovers coronaviruses with zoonotic potential

There has been limited characterisation of bat-borne coronaviruses in Europe. Here, we screened for coronaviruses in 48 faecal samples from 16 of the 17 bat species breeding in the UK, collected through a bat rehabilitation and conservationist network. We recovered nine (two novel) complete genomes across six bat species: four alphacoronaviruses, a MERS-related betacoronavirus, and four closely related sarbecoviruses. We demonstrate that at least one of these sarbecoviruses can bind and use the human ACE2 receptor for infecting human cells, albeit suboptimally. Additionally, the spike proteins of these sarbecoviruses possess an R-A-K-Q motif, which lies only one nucleotide mutation away from a furin cleavage site (FCS) that enhances infectivity in other coronaviruses, including SARS-CoV-2. However, mutating this motif to an FCS does not enable spike cleavage. Overall, while UK sarbecoviruses would require further molecular adaptations to infect humans, their zoonotic risk is unknown and warrants closer surveillance.

genomics↗

bioRxiv2022

Ancient herpes simplex 1 genomes reveal recent viral structure in Eurasia

Human herpes simplex virus 1 (HSV-1), a life-long infection spread by oral contact, today infects a majority of adults globally1, yet no ancient HSV-1 genomes have yet been published. Phylogeographic clustering of sampled diversity into European, pan-Eurasian, and African groups2, 3 has suggested that the virus co-diverged with anatomically modern humans migrating out of Africa4, although a much younger origin has also been proposed5. The lack of ancient HSV-1 genomes, high rates of recombination, and high mobility of humans in the modern era have impeded the understanding of HSV-1s evolutionary history. Here we present three full ancient European HSV-1 genomes and one partial genome, dating to between the 3rd and 17th century CE, sequenced to up to 9.5x with paired human genomes up to 10.16x. These HSV-1 strains fall within modern Eurasian diversity. We estimate a mean mutation rate of 7.6 x 10-7 - 1.13 x 10-6 for non-African diversity leading to an estimated age of sampled modern Eurasian diversity to 4.68 (3.87 - 5.65) kya. Extrapolation of these rates indicate the age of sampled HSV-1 to 5.29 (4.60-6.12 kya, suggesting lineage replacement coinciding with late Neolithisation and implicating Bronze Age migrations6 in the distribution of HSV-1 through Eurasia.

genomics↗

bioRxiv2021

A series of terribly unfortunate events: How environment and infection synergized to cause the Kihansi spray toad extinction

Outbreaks of emerging infectious diseases are trained by local biotic and abiotic factors, with host declines occurring when conditions favour the pathogen. Extinction of the Tanzanian Kihansi spray toad (Nectophrynoides asperginis) in 2004 was contemporaneous with the construction of a dam, implicating habitat modification in the loss of this species. However, high burdens of a globally emerging infection, Batrachochytrium dendrobatidis (Bd) were synchronously observed implicating infectious disease in this toads extinction. Here, by shotgun sequencing skin DNA from archived toad mortalities and assembling chytrid mitogenomes, we prove this outbreak was caused by the BdCAPE lineage and not the panzootic lineage BdGPL that is widely associated with global amphibian extinctions. Molecular dating showed an invasion of BdCAPE across Southern Africa overlapping with the timing of the extinction event. However, post-outbreak surveillance of conspecific species inhabiting this mountainous region showed widespread infection by BdCAPE yet no signs of amphibian ill-health or species decline. Our findings show that despite efforts to mitigate the environmental impact caused by dams construction, invasion of the pathogen ultimately led to the loss of the Kihansi spray toad; a synergism between emerging infectious disease and environmental change that likely heralds wider negative impacts on biodiversity in the Anthropocene.

ecology↗

bioRxiv2021

31,600-year-old human virus genomes support a Pleistocene origin for common childhood infections

The origins of viral pathogens and the age of their association with humans remains largely elusive. To date, there is no direct evidence about the diversity of viral infections in early modern humans pre-dating the Holocene. We recovered two near-complete genomes (5.2X and 0.7X) of human adenovirus C (HAdV-C), as well as low-coverage genomes from four distinct species of human herpesvirus obtained from two 31,630-year-old milk teeth excavated at Yana, in northeastern Siberia. Phylogenetic analysis of the two HAdV-C genomes suggests an evolutionary origin around 700,000 years ago consistent with a common evolutionary history with hominin hosts. Our findings push back the earliest direct molecular evidence for human viral infections by [~]25,000 years, and demonstrate that viral species causing common childhood viral infections today have been in circulation in humans at least since the Pleistocene.

evolutionary biology↗

bioRxiv2021

A phylogeny-based metric for estimating changes in transmissibility from recurrent mutations in SARS-CoV-2

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) emerged in late 2019 and spread globally to cause the COVID-19 pandemic. Despite the constant accumulation of genetic variation in the SARS-CoV-2 population, there was little evidence for the emergence of significantly more transmissible lineages in the first half of 2020. Starting around November 2020, several more contagious and possibly more virulent Variants of Concern (VoCs) were reported in various regions of the world. These VoCs share some mutations and deletions that haven arisen recurrently in distinct genetic backgrounds. Here, we build on our previous work modelling the association of mutations to SARS-CoV-2 transmissibility and characterise the contribution of individual recurrent mutations and deletions to estimated viral transmissibility. We then assess how patterns of estimated transmissibility in all SARS-CoV-2 clades have varied over the course of the COVID-19 pandemic by summing transmissibility estimates for all individual mutations carried by any sequenced genome analysed. Such an approach recovers the Delta variant (21A) as the most transmissible clade currently in circulation, followed by the Alpha variant (20I). By assessing transmissibility over the time of sampling, we observe a tendency for estimated transmissibility within clades to slightly decrease over time in most clades. Although subtle, this pattern is consistent with the expectation of a decay in transmissibility in mainly non-recombining lineages caused by the accumulation of weakly deleterious mutations. SARS-CoV-2 remains a highly transmissible pathogen, though such a trend could conceivably play a role in the turnover of different global viral clades observed over the pandemic so far. CaveatsO_LIThis work is not about the severity of disease. We do not analyse the severity of disease. We do not present any evidence that SARS-CoV-2 has decreased in severity. C_LIO_LILineage replacement dynamics are affected by many factors. The trend we recover for a decrease in inferred transmissibility of a clade over time is a small effect. We caution against over-interpretation. This result would not affect the management of the SARS-CoV-2 pandemic: for example, we make no claims about any impact on the efficacy of particular non-pharmaceutical interventions (NPIs). C_LIO_LIOur phylogeny-based method to infer changes in estimated transmissibility due to recurrent mutations and deletions makes a number of simplifying assumptions. These may not all be valid. The consistent trend for the slight decrease we report might be due to an as-yet-unidentified systematic bias. C_LI

genomics↗

bioRxiv2021

Role of the mobilome in the global dissemination of the carbapenem resistance gene blaNDM

The mobile resistance gene blaNDM encodes the NDM enzyme which hydrolyses carbapenems, a class of antibiotics used to treat some of the most severe bacterial infections. blaNDM is globally distributed across a variety of Gram-negative bacteria on multiple plasmids, typically located within a highly recombining and transposon-rich genomic region. This complexity means the dynamics underlying the dissemination of blaNDM remain poorly resolved. In this work, we compile a dataset of over 6000 bacterial genomes harbouring the blaNDM gene including 104 newly generated PacBio hybrid assemblies from clinical and livestock associated isolates across China. We develop a novel computational approach to track structural variants surrounding blaNDM in bacterial genomes. This allows us to identify the prevalent genomic contexts of blaNDM and reconstruct the key mobile genetic elements and events in its global spread. We estimate that blaNDM emerged on a Tn125 transposon before 1985 but only reached a global prevalence around a decade after its first recorded observation in 2005. We find that the Tn125 transposon played an important role in early plasmid-mediated jumps of blaNDM but was overtaken by other elements in recent years including IS26-flanked pseudo-composite transposons and Tn3000. Lastly, we observe a notable correlation between plasmid backbones bearing blaNDM and the sampling location of isolates. This observation suggests that the dissemination of resistance genes is mainly driven by successive between-plasmid transposon jumps, with plasmid exchange much more restricted due to the adaptation of plasmids to specific bacterial hosts.

microbiology↗

bioRxiv2020

No detectable signal for ongoing genetic recombination in SARS-CoV-2

The COVID-19 pandemic has led to an unprecedented global sequencing effort of its viral agent SARS-CoV-2. The first whole genome assembly of SARS-CoV-2 was published on January 5 2020. Since then, over 150,000 high-quality SARS-CoV-2 genomes have been made available. This large genomic resource has allowed tracing of the emergence and spread of mutations and phylogenetic reconstruction of SARS-CoV-2 lineages in near real time. Though, whether SARS-CoV-2 undergoes genetic recombination has been largely overlooked to date. Recombination-mediated rearrangement of variants that arose independently can be of major evolutionary importance. Moreover, the absence of recombination is a key assumption behind the application of phylogenetic inference methods. Here, we analyse the extant genomic diversity of SARS-CoV-2 and show that, to date, there is no detectable hallmark of recombination. We assess our detection power using simulations and validate our method on the related MERS-CoV for which we report evidence for widespread genetic recombination.

genomics↗

bioRxiv2020

Pre-existing T cell-mediated cross-reactivity to SARS-CoV-2 cannot solely be explained by prior exposure to endemic human coronaviruses

Several studies have reported the presence of pre-existing humoral or cell-mediated cross-reactivity to SARS-CoV-2 peptides in healthy individuals unexposed to SARS-CoV-2. In particular, the current literature suggests that this pre-existing cross-reactivity could, in part, derive from prior exposure to common cold endemic human coronaviruses (HCoVs). In this study, we characterised the sequence homology of SARS-CoV-2-derived T-cell epitopes reported in the literature across the entire diversity of the Coronaviridae family. Slightly over half (54.8%) of the tested epitopes did not have noticeable homology to any of the human endemic coronaviruses (HKU1, OC43, NL63 and 229E), suggesting prior exposure to these viruses cannot explain the full cross-reactive profiles observed in healthy unexposed individuals. Further, we find that the proportion of cross-reactive SARS-CoV-2 epitopes with noticeable sequence homology is extremely well predicted by the phylogenetic distance to SARS-CoV-2 (R2 = 96.6%). None of the coronaviruses sequenced to date showed a statistically significant excess of T-cell epitope homology relative to the proportion of expected random matches given the sequence similarity of their core genome to SARS-CoV-2. Taken together, our results suggest that the repertoire of cross-reactive epitopes reported in healthy adults cannot be primarily explained by prior exposure to any coronavirus known to date, or any related yet-uncharacterised coronavirus.

immunology↗