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Iversen, A. K. N.

Publications and source records attributed to Iversen, A. K. N..

5 recordsLinked to original sources

A near-ubiquitous plasmid characterises Second Pandemic Yersinia pestis

Yersinia pestis, the causative agent of plague, crippled population across Eurasia in three well-described historical pandemics: The Justinianic plague (541-780), the Second Pandemic (1346-1840) and the Third Pandemic (1894-). The Second Pandemic was the deadliest, with the Black Death (1346-1351) killing up to 60% of Europe's population, far exceeding the population mortality of the Third pandemic, despite few genomic differences between their plague strains. To identify unique genetic variation that could help explain the high death toll of the Second Plague pandemic, we used variation-graph based pan-genomics on a large dataset of 110 new and 12 published shotgun sequenced ancient plague genomes to comprehensively characterise the pangenome diversity of the Second Pandemic plague. Our pangenomic approach revealed the presence of a cryptic 34kb plasmid, pTP33, in almost all strains from the Second Pandemic, but undetectable in all other ancient strains. We find that pTP33 is a phage-plasmid-like derived element with homologues in Enterobacterales bacteria with established insect- or invertebrate-associated lifestyle phases. Our results suggest that pTP33 widened the range and infectivity of vector species available for plague transmission, consistent with reported effects on biofilm formation and bacterial retention. We hypothesise that pTP33 broadened the vector range of Y. pestis beyond the classical rat/flea cycle, facilitating the establishment of new rodent-ectoparasite plague reservoirs, which, critically, increased the risk of flea- or lice-mediated plague transmission between humans. Taken together, our findings offer a biological explanation for differences in transmission dynamics and population mortality between the Second and Third plague pandemics.

genomics↗

Lethal Plague Outbreaks in Lake Baikal Hunter-gatherers 5500 Years Ago

The rise of zoonotic diseases in prehistory is often associated with the Neolithic agricultural transition1,2. In particular, plague has been linked to population declines in Late Neolithic Europe3,4. Although plague is amongst the most devastating diseases in human history, early strains of Yersinia pestis, the causal agent of plague, lack virulence factors required for the bubonic form5, and their severity remains unclear. Here, we describe the oldest strains of plague reported so far, associated with two early phases of outbreaks among prehistoric hunter-gatherers in the Lake Baikal region in East Siberia, beginning from [~]5600-5400 years ago (cal. BP). These outbreaks occur across four hunter-gatherer cemeteries; the largest of these (Ust-Ida I) has a 38.7% detection rate for plague infection (39% detection across all sites). By reconstructing kinship pedigrees, we show that small familial groups are affected, consistent with human-to-human spread of the disease, and the first outbreak occurred within a single generation. Intriguingly, the infections appear to have resulted in acute mortality events, especially among children. Zoonotic transmission is separately indicated by a Brucella infection in one of the children. Interestingly, we see differences in functional genomic variants in the prehistoric plague strains, including in the ypm superantigen known from Y. pseudotuberculosis today. The new strains diverge ancestrally to all known Y. pestis diversity and push back the Y. pestis divergence from Y. pseudotuberculosis by some 2000 years6. Our results show that plague outbreaks happen earlier than previously thought and that these early outbreaks were indeed lethal. The findings challenge the common notion that high population densities and lifestyle changes during the Neolithic transition were prerequisites for plague epidemics.

genetics↗

The landscape of ancient human pathogens in Eurasia from the Stone Age to historical times

Infectious diseases have had devastating impacts on human populations throughout history, but important questions about their origins and past dynamics remain1. To create the first archaeogenetic-based spatiotemporal map of human pathogens, we screened shotgun sequencing data from 1,313 ancient humans covering 37,000 years of Eurasian history. We demonstrate the widespread presence of ancient bacterial, viral and parasite DNA, identifying 5,486 individual hits against 492 species from 136 genera. Among those hits, 3,384 involve known human pathogens2, many of which were detected for the first time in ancient human remains. Grouping the ancient microbial species according to their likely reservoir and type of transmission, we find that most groups are identified throughout the entire sampling period. Intriguingly, zoonotic pathogens are only detected [~]6,500 years ago, peaking [~]5,000 years ago, coinciding with the widespread domestication of livestock3. Our findings provide the first direct evidence that this lifestyle change resulted in an increased infectious disease burden. Importantly, they also suggest that the spread of these pathogens increased substantially during subsequent millenia, coinciding with the pastoralist migrations from the Eurasian Steppe4,5.

evolutionary biology↗

Genetic risk for Multiple Sclerosis originated in Pastoralist Steppe populations

Multiple sclerosis (MS) is a modern neuro-inflammatory and -degenerative disease, which is most prevalent in Northern Europe. Whilst it is known that inherited risk to MS is located within or within close proximity to immune genes, it is unknown when, where and how this genetic risk originated 1. By using the largest ancient genome dataset from the Stone Age 2, along with new Medieval and post-Medieval genomes, we show that many of the genetic risk variants for MS rose to higher frequency among pastoralists located on the Pontic Steppe, and were brought into Europe by the Yamnaya-related migration approximately 5,000 years ago. We further show that these MS-associated immunogenetic variants underwent positive selection both within the Steppe population, and later in Europe, likely driven by pathogenic challenges coinciding with dietary, lifestyle, and population density changes. This study highlights the critical importance of this period as a determinant of modern immune responses and its subsequent impact on the risk of developing MS in a changing environment.

evolutionary biology↗

A simple, safe and sensitive method for SARS-CoV-2 inactivation and RNA extraction for RT-qPCR

The SARS-CoV-2 pandemic has created an urgent need for large amounts of diagnostic tests to detect viral RNA, which commercial suppliers are increasingly unable to deliver. In addition to the lack of availability, the current methods do not always fully inactivate the virus. Together, this calls for the development of safer methods for extraction and detection of viral RNA from patient samples that utilise readily available reagents and equipment present in most standard laboratories. We present a rapid and straightforward RNA extraction protocol for inactivating the SARS-CoV-2 virus that uses standard lab reagents. This protocol expands analysis capacity as the inactivated samples can be used in RT-qPCR detection tests at laboratories not otherwise classified for viral work. The method circumvents the need for commercial RNA purification kits, takes about 30 minutes from swab to PCR-ready viral RNA, and enables downstream detection of SARS-CoV-2 by RT-qPCR with very high sensitivity (~4 viral RNA copies per RT-qPCR). In summary, we present a rapid, safe and sensitive method for high-throughput detection of SARS-CoV-2, that can be conducted in any laboratory equipped with a qPCR machine.

microbiology↗