Biology subjects

Hovhannisyan, A.

Publications and source records attributed to Hovhannisyan, A..

10 recordsLinked to original sources

bioRxiv2026

Plague-driven selection enriched familial Mediterranean fever mutations in Armenia

The discovery that positive selection due to resistance to malarial infection maintained the prevalence of sickle cell and other disease alleles was a landmark in evolution, genetics and epidemiology. Mutations in the MEFV gene causing familial Mediterranean fever with high frequency in Eastern Mediterranean populations give the only other strong candidates for a similar process. Here we estimate a pathogenic MEFV mutation burden in Armenians with a carrier rate of ~41%: a worldwide maximum. By combining these data with regional ancient MEFV genotypes spanning more than 60 centuries, we establish that the allele frequencies of three mutations M694V, M680I, and V726A underwent recent rapid increases, indicating positive selection with an onset consistent with the first Yersinia pestis plague pandemic, ~541 CE to 767 CE or even earlier in time, echoing functional data implying resistance to this infection as the selective agent. This extends to three the number of MEFV variants for which there is evidence for strong concurrent selection at this locus in the Eastern Mediterranean, making it unlikely that this geographic peak resulted from chance alone. Although bubonic plague was extremely widespread, the restricted geography of this selection points toward the Eastern Mediterranean as a longstanding enzootic centre with continuous recycling of outbreaks.

genomics↗

bioRxiv2026

Short-term synaptic plasticity at neuron-OPC synapses in the corpus callosum during postnatal development of mice: experimental and computational study

Neuronal circuits rely on precisely timed synaptic transmission and plasticity, which are established through activity-dependent maturation during development. While these processes are well characterized at neuronal synapses, far less is known about how synaptic communication between neurons and glial cells develops. Pyramidal cortical neurons project axons through white matter where they release glutamate ectopically along their shafts and form glutamatergic synapses with oligodendrocyte precursor cells (OPCs). The functional maturation of these neuron-glia connections remains unknown. Here, using single-cell electrophysiology combined with computational modelling, we show that neuron-OPC synapses in the mouse corpus callosum undergo a pronounced developmental transformation in short-term synaptic plasticity. During the first two postnatal months, these synapses switch from strong synaptic depression to facilitation. This transition is accompanied by a shortening of synaptic delay and a reduction in asynchronous glutamate release, indicating an increase in temporal precision of neurotransmitter signalling in white matter. Computational modelling suggests that both pre- and postsynaptic changes may underlie this functional maturation. Taken together, our findings demonstrate that neuron-OPC synapses in white matter are not static but undergo developmental transition towards facilitation and temporally precise transmission that parallels the maturation trajectory of classical neuronal synapses in cortical grey matter. These results identify neuron-glia synapses in white matter as dynamic elements of developing neural circuits, and suggest that synaptic release machineries at axonal shafts in white matter and synaptic boutons in grey matter mature in a similar fashion.

neuroscience↗

bioRxiv2025

Climate Shaped the Global Population Structure of Leopards and their Extinction in Europe

Environmental change is often invoked as a key force shaping species evolution and demography, but quantifying its role is challenging. Leopards (Panthera pardus), a widely distributed generalist species, provide an ideal case for studying the role of the environment. The population dynamics of African and Asian leopards differ dramatically, with near panmixia in Africa versus a strong structure and eight subspecies in Asia. Fossil records show that a population in Europe disappeared after the Last Glacial Maximum (LGM), further pointing to complex range dynamics in Eurasia. In this study, we explicitly test the role of climate in shaping leopards population dynamics across the continents, by quantitatively combining paleoclimatic, demographic, and genetic simulations over the last 450 thousand years. Using an Approximate Bayesian Computational framework, we show that the genetic structure differences between Africa and Asia can be explained by distinct historical climatic conditions in these two continents: most of sub-Saharan Africa and parts of Southeast Asia exhibited a stable range without geographical barriers, while other areas such as Morocco, Afghanistan and Northeast Asia showed expansion and extinction cycles during glacial and interglacials. We further model population dynamics in Europe and validate it against fossil and radiocarbon dates records. We find that European populations were likely fragile, with extinctions repeatedly predicted over multiple glacial cycles, indicating that climate change possibly led to the extinction of the European subspecies following the LGM. Notably, we found that climate during the Holocene should have allowed a more recent recolonisation that did not happen, indicating other factors such as human presence might have blocked it.

zoology↗

bioRxiv2025

Palaeoproteomic and genetic insights into millennial-scale dairy consumption in Armenia

Dairy products are a key component of the diet in Armenia today, yet the origins of milk consumption, its historical development, and genetic adaptations related to milk digestion in the region remain understudied. Here, we investigate the co-evolution of dairying practices and lactase persistence in Armenia through combined palaeoproteomic and genetic analyses spanning from prehistory to the present. Our palaeoproteomic results provide direct evidence for milk consumption in prehistoric Armenia and, in conjunction with existing regional data, indicate that dairying was an established component of the South Caucasus subsistence economy from at least the late fourth millennium BCE. We found evidence of milk consumption from multiple species across archaeological periods, with cattle milk representing the earliest confirmed evidence from the Chalcolithic period. Notably, milk proteins were predominantly recovered from high-altitude sites, suggesting that dairy consumption served as an adaptive strategy for harsh highland environmental conditions. In contrast to the widespread evidence for milk consumption, our genetic findings indicate that the lactase persistence-associated variants never reached high frequencies throughout Armenian prehistory. This pattern suggests that the relatively low frequency of lactase persistence may reflect a predominant cultural adaptation to the fermentation of dairy products, which reduces lactose content and enables dairy use even in genetically lactose-intolerant populations.

evolutionary biology↗

bioRxiv2025

tidygenclust: Clustering for Population Genetics in R

BackgroundPopulation structure analysis is crucial for evolutionary research and medical genomics. Clustering methods, broadly categorized as model-based (e.g. ADMIXTURE) or non-model-based (e.g. SCOPE), differ in their methodology and computational efficiency. Recently, fastmixture, a model-based approach, has improved scalability and performance, while replicate alignment tools, such as Clumppling, extend previous methods by also aligning the modes across K values. However, all the existing tools are standalone and generate numerous untracked text files, as well as offering limited plot customisability. ResultsWe introduce an R package, tidygenclust, which brings the functionalities of the original ADMIXTURE, fastmixture and Clumppling software into R, enabling a streamlined and integrated workflow. By integrating with tidypopgen, a package designed to handle large SNP datasets, these new tools maintain metadata, simplify data handling, and produce results as customisable ggplot2 objects for flexible visualisation. ConclusionsThe R package tidygenclust advances population genetic analysis by combining computational efficiency with reproducible workflows and user-friendly plotting. The source code and instructions can be accessed on https://github.com/EvolEcolGroup/tidygenclust.

bioinformatics↗

bioRxiv2025

Pan-African metapopulation model explains Homo sapiens genetic and morphological evolution

A growing body of evidence has challenged the traditional assumption of a single-region origin for Homo sapiens, suggesting instead that our species originated from multiple geographically distinct populations in Africa, which intermittently exchanged genes and culture. However, our understanding of how this Pan-African metapopulation would have evolved through time is still limited. Furthermore, the drivers of such changes are uncertain, and quantitative models of the respective contributions of different African regions are lacking. Here we provide a complete reconstruction of the meta-population dynamics over the last 200,000 years by quantitatively integrating an ecological niche model, informed by archaeological sites, within a spatially explicit population genetic framework. The inferred metapopulation dynamics account for the divergence among all available contemporary and ancient genomes of African hunter-gatherers used to calibrate the model. In addition, it also accurately predicts the patterns of craniometric diversification across the continent from the Late Middle Pleistocene to the present. Finally, we show how the climate-driven changes in population sizes and connectivity are congruent with major patterns of archaeological and phenotypic diversification over the last 200,000 years across the African continent.

evolutionary biology↗

bioRxiv2021

Climate and mountains shaped human ancestral genetic lineages

Extensive sequencing of modern and ancient human genomes has revealed that contemporary populations can be explained as the result of recent mixing of a few distinct ancestral genetic lineages1. But the small number of aDNA samples that predate the Last Glacial Maximum means that the origins of these lineages are not well understood. Here, we circumvent the limited sampling by modelling explicitly the effect of climatic changes and terrain on population demography and migrations through time and space, and show that these factors are sufficient to explain the divergence among ancestral lineages. Our reconstructions show that the sharp separation between African and Eurasian lineages is a consequence of only a few limited periods of connectivity through the arid Arabian peninsula, which acted as the gate out of the Arican continent. The subsequent spread across Eurasia was then mostly shaped by mountain ranges, and to a lesser extent deserts, leading to the split of European and Asians, and the further diversification of these two groups. A high tolerance to cold climates allowed the persistence at high latitudes even during the Last Glacial Maximum, maintaining a pocket in Beringia that led to the later, rapid colonisation of the Americas. The advent of food production was associated with an increase in movement2, but mountains and climate have been shown to still play a major role even in this latter period3,4, affecting the mixing of the ancestral lineages that we have shown to be shaped by those two factors in the first place.

genomics↗

bioRxiv2020

A curated dataset of modern and ancient high-coverage shotgun human genomes.

Over the last few years, genome-wide data for a large number of ancient human samples have been collected. Whilst datasets of capture SNPs have been collated, high coverage shotgun genomes (which are relatively few but allow certain type of analyses not possible with ascertained captured SNPs) have to be reprocessed by individual groups from raw reads. This task is computationally intensive. Here, we release a dataset including 34 whole-genome sequenced samples, previously published and distributed worldwide, together with the genetic pipeline used to process them. The dataset contains 73,435,604 sites called across 18 ancient and 16 modern individuals and includes sequence data from four previously published ancient samples which we sequenced to higher coverage (10-18x). Such a resource will allow researchers to analyse their new samples with the same genetic pipeline and directly compare them to the reference dataset without re-processing published samples. Moreover, this dataset can be easily expanded to increase the sample distribution both across time and space.

genomics↗

bioRxiv2020

Evaluation Of The Quercetin Semisynthetic Derivatives Interaction With Breast Cancer Resistance Protein

Breast cancer resistance protein (BCRP, ABCG2) is one of the ATP binding cassette (ABC) transporter proteins which involved in multi-drug resistance of cancer therapy. BCRP is expressed in various types of human cancer and inhibiting can be a solution to overcome multidrug resistance. Significant effort has been devoted to develop treatment strategies to overcome BCRP-mediated resistance. In addition, BCRP is expressed also in many normal tissues and plays an important role in drug absorption, distribution, and elimination. In order to design an effective cancer treatment strategy, a lot of flavones and their derivatives are used as anticancer drug compounds. One of the most promising flavonols is quercetin and quercetin semisynthetic derivatives which can inhibit the expression of BCRP. HighlightsO_LIVirtual screening using multiple docking program for consensus predictions. C_LIO_LIVirtual screening of the quercetin derivatives as potential inhibitors of BCRP. C_LIO_LISelected derivatives bind to the main amino acids of proteins. C_LIO_LISelected derivatives meet the criteria necessary for their consideration as drugs. C_LI

bioinformatics↗

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↗