Biology subjects

Nielsen, S. D.

Publications and source records attributed to Nielsen, S. D..

5 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

Genomic impact of the second plague pandemic on three human populations

The second plague pandemic (early 14th-early 19th centuries), which was caused by Yersinia pestis, had a profound demographic, socio-economic and cultural impact across Eurasia and North Africa. Many regions in Europe and the Middle East are estimated to have lost 40-60% of their human populations, with some areas suffering even higher mortality. Whether exposure to Y. pestis drove strong positive selection on protective genetic variants in the human genome, and how it shaped migration patterns, remains debated, despite several recent studies based on ancient DNA. Here, we analyse a markedly larger, higher coverage, and geographically diverse dataset based on shotgun sequencing of genomes from 529 ancient individuals to a mean depth 8.8x dating to either before or after the arrival of the pandemic at three sites in northern Europe: Trondheim (Norway), Lund (Sweden) and Vilnius (Lithuania). Genome-wide scans for signatures of selection provide no evidence for strong positive selection acting on specific genetic variants driven by Y. pestis exposure: we neither replicate selection signatures reported by previous studies nor identify new genome-wide significant candidates. However, for all three sites, we observe evidence for a reduction in long-range immigration, indicated by a drop in the diversity of ancestry that followed the arrival of Y. pestis and broadly coincided with the end of the Viking Age, Christianisation and the onset of the Little Ice Age. Our results shed important light on the demographic impact of major sociohistorical changes that occurred during the late Medieval period in Scandinavia and the Baltic region and link Christianisation to increased diversity in ancestry before the pandemic.

genomics↗

bioRxiv2026

Conservation rescued the Mauritius kestrel from extinction but not from genomic erosion

Conservation can prevent species extinction via demographic recovery, yet it remains debated whether this translates into genomic recovery and restored fitness. The Mauritius kestrel (Falco punctatus) declined to four known wild birds in 1974 before intensive management recovered the population. Using 130 genomes spanning nearly 200 years, lifetime reproductive success data, and simulations, we reconstructed genomic change across the species collapse and recovery. Long-term small population size had already removed some harmful variation before the crash, a process expected to buffer populations from severe inbreeding depression. Yet the recent bottleneck sharply increased inbreeding, exposed additional harmful variants, and left a signature of genomic erosion associated with reduced reproductive success. The long conservation history of the Mauritius kestrel shows how population collapse and recovery can leave a compounding genetic threat, in which partial genetic purging, continuing genomic erosion, and conservation dependence unfold together in rescued species.

evolutionary biology↗

bioRxiv2025

Genomic erosion through the lens of comparative genomics

Loss of genetic diversity threatens species survival, yet the dynamics of such loss and species responses thereof can vary widely depending on their evolutionary histories, life-history traits and demographic trajectories. Comparative genomics offers a powerful framework to explore the dynamics of genomic erosion across species. Here, we analysed the genomes of three species -- the Mauritius parakeet, the Mauritius kestrel, and the pink pigeon -- that experienced extreme and well-documented population bottlenecks. We compared them to 36 species spanning the avian phylogeny, with varied IUCN Red List statuses to investigate the genomic consequences of their demographic collapses. For each species, we assessed nucleotide diversity, genetic load, and runs of homozygosity (ROH), alongside genome synteny and transposable elements. We found a negative correlation between nucleotide diversity and ROH, but neither metric was a good predictor of the species Red List status. Rather, the population effective to census size ratio showed a strong correlation to Red List status. Moreover, species with larger historical effective population sizes showed greater heterozygosity but carried a higher heterozygous load, highlighting the importance of historical demography to assess species vulnerability to genomic erosion. We found significant differences in homozygous load between taxonomic groups of our target species, possibly due to differences in life-history traits and demographic histories. Genome structure analyses revealed differences in transposable elements and genomic rearrangements between groups, suggesting their potential role in shaping genome architecture and adaptive potential across species. Our findings underscore the value of multispecies comparisons in understanding the evolutionary dynamics of genomic erosion and its relevance for biodiversity conservation.

genomics↗

bioRxiv2021

Distinct SARS-CoV-2 sensing pathways in pDCs driving TLR7-antiviral vs. TLR2-immunopathological responses in COVID-19

Understanding the molecular pathways driving the acute antiviral and inflammatory response to SARS-CoV-2 infection is critical for developing treatments for severe COVID-19. Here we show that in COVID-19 patients, circulating plasmacytoid dendritic cells (pDCs) decline early after symptom onset and this correlated with COVID-19 disease severity. This transient depletion coincides with decreased expression of antiviral type I IFN and the systemic inflammatory cytokines CXCL10 and IL-6. Importantly, COVID-19 disease severity correlated with decreased pDC frequency in peripheral blood. Using an in vitro stem cell-based human pDC model, we demonstrate that pDCs directly sense SARS-CoV-2 and in response produce multiple antiviral (IFN and IFN{lambda}1) and inflammatory (IL-6, IL-8, CXCL10) cytokines. This immune response is sufficient to protect epithelial cells from de novo SARS-CoV-2 infection. Targeted deletion of specific sensing pathways identified TLR7-MyD88 signaling as being crucial for production of the antiviral IFNs, whereas TLR2 is responsible for the inflammatory IL-6 response. Surprisingly, we found that SARS-CoV-2 engages the neuropilin-1 receptor on pDCs to mitigate the antiviral IFNs but not the IL-6 response. These results demonstrate distinct sensing pathways used by pDCs to elicit antiviral vs. immunopathological responses to SARS-CoV-2 and suggest that targeting neuropilin-1 on pDCs may be clinically relevant for mounting TLR7-mediated antiviral protection. One Sentence SummarypDCs sense SARS-CoV-2 and elicit antiviral protection of lung epithelial cells through TLR7, while recognition of TLR2 elicits an IL-6 inflammatory response associated with immunopathology. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=163 SRC="FIGDIR/small/469755v1_ufig1.gif" ALT="Figure 1"> View larger version (35K): org.highwire.dtl.DTLVardef@fe64daorg.highwire.dtl.DTLVardef@18f4278org.highwire.dtl.DTLVardef@54de50org.highwire.dtl.DTLVardef@1cf67cb_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical abstract:C_FLOATNO SARS-CoV-2 sensing by plasmacytoid dendritic cells. SARS-CoV-2 is internalized by pDCs via a yet unknown endocytic mechanism. The intracellular TLR7 sensor detects viral RNA and induces a signaling cascade involving MyD88-IRAK4-TRAF6 (1) to induce CXCL10 and, via IRF7 phosphorylation and translocation, inducing type I and III Interferons (2). Once secreted, type I and III IFNs initiate autocrine and paracrine signals that induce the expression of IFN stimulated genes (ISGs), thereby facilitating an antiviral response that can protect the cell against infection. However, SARS-CoV-2, has the intrinsic property to facilitate CD304 signaling, potentially by interfering with IRF7 nuclear translocation, thereby inhibiting type I IFN production and thus reducing the antiviral response generated by the pDC (4). Furthermore, the SARS-CoV-2 envelope (E) glycoprotein is sensed by the extracellular TLR2/6 heterodimer and this facilitates production of the inflammatory IL-6 cytokine (5). Illustration was created with BioRender.com C_FIG

immunology↗