Biology subjects

Margaryan, A.

Publications and source records attributed to Margaryan, A..

13 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

Intracellular pH dynamics promotes zebrafish larval tail regeneration

Intracellular pH (pHi) dynamics regulates numerous cell behaviors, including migration and proliferation. While these functions are well-established in cell lines, the role of pHi changes in vivo is less well understood. We generated a transgenic zebrafish line expressing a fluorescent ratiometric pHi biosensor and identified functional changes in pHi during zebrafish larval tail regeneration. We found that tail amputation led to a transient decrease in pHi, followed by a prolonged increase in pHi above pre-amputation values. Moreover, we showed that pharmacologically inhibiting Na+/H+ exchanger (NHE) activity or decreasing extracellular pH attenuated the post-amputation increase in pHi, reduced subsequent cell proliferation, and impaired tail regeneration. We further found that inhibiting NHE activity post-amputation led to elevated inflammation, disrupted myeloid cell behavior, decreased reactive oxygen species, and increased glycogen synthase kinase-3 (GSK3) activity. Finally, we showed that the regeneration defects in larvae with disrupted pHi were partially rescued by the GSK3 inhibitor BIO. Our data reveal a previously unrecognized role for pHi dynamics in coordinating tissue behaviors in vivo and enabling zebrafish larval tail regeneration.

developmental biology↗

bioRxiv2024

Ancient biomolecular analysis of 39 mammoth individuals from Kostenki 11-Ia elucidates Upper Palaeolithic human resource use

Circular structures made from woolly mammoth bones are found across Ukraine and west Russia, yet the origin of the bones remains uncertain. We present ten new mammoth radiocarbon dates from the largest circular structure at Kostenki 11-Ia, identifying two mammoth mandibles [~]200-1,200 years older than the other dated materials from the site, suggesting skeletal material from long-dead individuals was scavenged and used in the site construction. Biomolecular sexing of 30 individuals showed a predominance of females, suggesting the Kostenki mammoths are primarily from herds. We identify six mitochondrial lineages across 16 samples, showing they are not all from the same matriline. Integrating biomolecular sexing with stable{delta} 13C and{delta} 15N isotope analysis, we find no isotopically-differentiated resource use by females and males, providing the first analysis of foraging differences between sexes in any Late Pleistocene megafauna. Our study highlights the significance of integrating ancient biomolecular approaches in archaeological inference. TeaserIntegrating 14C dating, ancient DNA, palaeoproteomics, and stable isotopes improves our understanding of Kostenki 11-Ia

evolutionary biology↗

bioRxiv2023

A genomic exploration of the possible de-extirpation of the Zanzibar leopard

The recently extirpated Zanzibar leopard was the only known African leopard (Panthera pardus spp.) population restricted exclusively to a major island habitat. Although its demise was driven through habitat change and conflict with humans, given its role as a keystone species for the Zanzibar Archipelago, its potential reintroduction might offer a means for helping preserve the natural biodiversity of its former habitat. Whether this is feasible, however, would be contingent on both whether closely related source populations can be identified on mainland Africa, and whether the Zanzibar form exhibited any special adaptations that might need to be considered when choosing such a source. In light of these questions, we genomically profiled two of the six known historic specimens, to explore whether they represent a realistic candidate for de-extirpation through reintroduction. Our analyses indicate that despite its geographic separation, the Zanzibar leopard shared a close genetic relationship with mainland East African individuals. Furthermore, although its uniqueness as an island population was emphasised by genomic signatures of high inbreeding and increased mutation load, the latter similar to the level of the critically endangered Amur leopard (P. p. orientalis), we find no evidence of positive selection unique to Zanzibar. We therefore conclude that should attempts to restore leopards to Zanzibar be planned, then mainland East African leopards would provide a suitable gene pool, whether using genetic engineering or conventional rewilding approaches.

evolutionary biology↗

bioRxiv2022

Population Genomics of Stone Age Eurasia

Western Eurasia witnessed several large-scale human migrations during the Holocene1-5. To investigate the cross-continental impacts we shotgun-sequenced 317 primarily Mesolithic and Neolithic genomes from across Northern and Western Eurasia. These were imputed alongside published data to obtain diploid genotypes from >1,600 ancient humans. Our analyses revealed a Great Divide genomic boundary extending from the Black Sea to the Baltic. Mesolithic hunter-gatherers (HGs) were highly genetically differentiated east and west of this zone, and the impact of the neolithisation was equally disparate. Large-scale ancestry shifts occurred in the west as farming was introduced, including near-total replacements of HGs in many areas, whereas no substantial ancestry shifts happened east of the zone during the same period. Similarly, relatedness decreased in the west from the Neolithic transition onwards, while east of the Urals relatedness remained high until [~]4,000 BP, consistent with persistence of localised HG groups. The boundary dissolved when Yamnaya-related ancestry spread across western Eurasia around 5,000 BP resulting in a second major turnover that reached most parts of Europe within a 1,000-year span. The genetic origin and fate of the Yamnaya have remained elusive but we demonstrate that HGs from the Middle Don region contributed ancestry to them. Yamnaya-groups later admixed with individuals associated with the Globular Amphora Culture before expanding into Europe. Similar turnovers occurred in western Siberia, where we report new genomic data from a Neolithic steppe cline spanning the Siberian forest steppe to Lake Baikal. These prehistoric migrations had profound and lasting effects on the genetic diversity of Eurasian populations.

evolutionary biology↗

bioRxiv2021

Genomic ancestry, diet and microbiomes of Upper Palaeolithic hunter-gatherers from San Teodoro cave (Sicily, Italy)

Recent improvements in the analysis of ancient biomolecules from human remains and associated dental calculus have provided new insights into the prehistoric diet and past genetic diversity of our species. Here we present a "multi-omics" study, integrating genomic and proteomic analyses of two post-Last Glacial Maximum (LGM) individuals from San Teodoro cave (Italy), to reconstruct their lifestyle and the post-LGM resettlement of Europe. Our analyses show genetic homogeneity in Sicily during the Palaeolithic, representing a hitherto unknown Italian genetic lineage within the previously identified "Villabruna cluster". We argue that this lineage took refuge in Italy during the LGM, followed by a subsequent spread to central-western Europe. Multi-omics analysis of dental calculus showed a diet rich of animal proteins which is also reflected on the oral microbiome composition. Our results demonstrate the power of using a multi-omics approach in the study of prehistoric human populations.

genetics↗

bioRxiv2021

Towards the extended barcode concept: Generating DNA reference data through genome skimming of danish plants

BackgroundRecently, there has been a push towards the extended barcode concept of utilising chloroplast genomes (cpGenome) and nuclear ribosomal DNA (nrDNA) sequences for molecular identification of plants instead of the standard barcode regions. These extended barcodes has a wide range of applications, including biodiversity monitoring and assessment, primer design, and evolutionary studies. However, these extended barcodes are not well represented in global reference databases. To fill this gap, we generated cpGenomes and nrDNA reference data from genome skims of 184 plant species collected in Denmark. We further explored the application of our generated reference data for molecular identifications of plants in an environmental DNA metagenomics study. ResultsWe assembled partial cpGenomes for 82.1% of sequenced species and full or partial nrDNA sequences for 83.7% of species. We added all assemblies to GenBank, of which chloroplast reference data from 101 species and nuclear reference data from 6 species were not previously represented. On average, we recovered 45 genes per species. The rate of recovery of standard barcodes was higher for nuclear barcodes (>89%) than chloroplast barcodes (< 60%). Extracted DNA yield did not affect assembly outcome, whereas high GC content did so negatively. For the in silico simulation of metagenomic reads, taxonomic assignments using the reference data generated had better species resolution (94.9%) as compared to GenBank (18.1%) without any identification errors. ConclusionsGenome skimming generates reference data of both standard barcodes and other loci, contributing to the global DNA reference database for plants.

genomics↗

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↗

bioRxiv2020

AN ADMIXTURE SIGNAL IN ARMENIANS AROUND THE END OF THE BRONZE AGE REVEALS WIDESPREAD POPULATION MOVEMENT ACROSS THE MIDDLE EAST

The Armenians, a population inhabiting the region in West Asia known as the Armenian Highland, has been argued to show a remarkable degree of population continuity since the Early Neolithic. Here we test the degree of continuity of this population as well as its plausible origin, by collating modern and ancient genomic data, and adding a number of novel contemporary genomes. We show that Armenians have indeed remained unadmixed through the Neolithic and at least until the first part of the Bronze Age, and fail to find any support for historical suggestions by Herodotus of an input from the Balkans. However, we do detect a genetic input of Sardinian-like ancestry during or just after the Middle-Late Bronze Age. A similar input at approximately the same time was detected in East Africa, suggesting large-scale movement both North and South of the Middle East. Whether such large-scale population movement was a result of climatic or cultural changes is unclear, as well as the true source of gene flow remains an open question that needs to be addressed in future ancient DNA studies.

genomics↗

bioRxiv2020

Historical population declines prompted significant genomic erosion in the northern and southern white rhinoceros (Ceratotherium simum)

Large vertebrates are extremely sensitive to anthropogenic pressure, and their populations are declining fast. The white rhinoceros (Ceratotherium simum) is a paradigmatic case: this African megaherbivore suffered a remarkable population reduction in the last 150 years due to human activities. The two white rhinoceros subspecies, the northern (NWR) and the southern white rhinoceros (SWR), however, underwent opposite fates: the NWR vanished quickly after the onset of the decline, while the SWR recovered after a severe bottleneck. Such demographic events are predicted to have an erosive effect at the genomic level, in connection with the extirpation of diversity, and increased genetic drift and inbreeding. However there is currently little empirical data available that allows us to directly reconstruct the subtleties of such processes in light of distinct demographic histories. Therefore to assess these effects, we generated a whole-genome, temporal dataset consisting of 52 re-sequenced white rhinoceros genomes, that represents both subspecies at two time windows: before and during/after the bottleneck. Our data not only reveals previously unknown population substructure within both subspecies, but allowed us to quantify the genomic erosion undergone by both, with post-bottleneck white rhinoceroses harbouring significantly fewer heterozygous sites, and showing higher inbreeding coefficients than pre-bottleneck individuals. Moreover, the effective population size suffered a decrease of two and three orders of magnitude in the NWR and SWR respectively, due to the recent bottleneck. Our data therefore provides much needed empirical support for theoretical predictions about the genomic consequences of shrinking populations, information that is relevant for understanding the process of population extinction. Furthermore, our findings have the potential to inform management approaches for the conservation of the remaining white rhinoceroses.

evolutionary biology↗

bioRxiv2019

Population genomics of the Viking world

The Viking maritime expansion from Scandinavia (Denmark, Norway, and Sweden) marks one of the swiftest and most far-flung cultural transformations in global history. During this time (c. 750 to 1050 CE), the Vikings reached most of western Eurasia, Greenland, and North America, and left a cultural legacy that persists till today. To understand the genetic structure and influence of the Viking expansion, we sequenced the genomes of 442 ancient humans from across Europe and Greenland ranging from the Bronze Age (c. 2400 BC) to the early Modern period (c. 1600 CE), with particular emphasis on the Viking Age. We find that the period preceding the Viking Age was accompanied by foreign gene flow into Scandinavia from the south and east: spreading from Denmark and eastern Sweden to the rest of Scandinavia. Despite the close linguistic similarities of modern Scandinavian languages, we observe genetic structure within Scandinavia, suggesting that regional population differences were already present 1,000 years ago. We find evidence for a majority of Danish Viking presence in England, Swedish Viking presence in the Baltic, and Norwegian Viking presence in Ireland, Iceland, and Greenland. Additionally, we see substantial foreign European ancestry entering Scandinavia during the Viking Age. We also find that several of the members of the only archaeologically well-attested Viking expedition were close family members. By comparing Viking Scandinavian genomes with present-day Scandinavian genomes, we find that pigmentation-associated loci have undergone strong population differentiation during the last millennia. Finally, we are able to trace the allele frequency dynamics of positively selected loci with unprecedented detail, including the lactase persistence allele and various alleles associated with the immune response. We conclude that the Viking diaspora was characterized by substantial foreign engagement: distinct Viking populations influenced the genomic makeup of different regions of Europe, while Scandinavia also experienced increased contact with the rest of the continent.

genetics↗

bioRxiv2018

The population history of northeastern Siberia since the Pleistocene

Far northeastern Siberia has been occupied by humans for more than 40 thousand years. Yet, owing to a scarcity of early archaeological sites and human remains, its population history and relationship to ancient and modern populations across Eurasia and the Americas are poorly understood. Here, we analyze 34 ancient genome sequences, including two from fragmented milk teeth found at the ~31.6 thousand-year-old (kya) Yana RHS site, the earliest and northernmost Pleistocene human remains found. These genomes reveal complex patterns of past population admixture and replacement events throughout northeastern Siberia, with evidence for at least three large-scale human migrations into the region. The first inhabitants, a previously unknown population of \"Ancient North Siberians\" (ANS), represented by Yana RHS, diverged ~38 kya from Western Eurasians, soon after the latter split from East Asians. Between 20 and 11 kya, the ANS population was largely replaced by peoples with ancestry related to present-day East Asians, giving rise to ancestral Native Americans and \"Ancient Paleosiberians\" (AP), represented by a 9.8 kya skeleton from Kolyma River. AP are closely related to the Siberian ancestors of Native Americans, and ancestral to contemporary communities such as Koryaks and Itelmen. Paleoclimatic modelling shows evidence for a refuge during the last glacial maximum (LGM) in southeastern Beringia, suggesting Beringia as a possible location for the admixture forming both ancestral Native Americans and AP. Between 11 and 4 kya, AP were in turn largely replaced by another group of peoples with ancestry from East Asia, the \"Neosiberians\" from which many contemporary Siberians derive. We detect gene flow events in both directions across the Bering Strait during this time, influencing the genetic composition of Inuit, as well as Na Dene-speaking Northern Native Americans, whose Siberian-related ancestry components is closely related to AP. Our analyses reveal that the population history of northeastern Siberia was highly dynamic throughout the Late Pleistocene and Holocene. The pattern observed in northeastern Siberia, with earlier, once widespread populations being replaced by distinct peoples, seems to have taken place across northern Eurasia, as far west as Scandinavia.

genomics↗