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PubMed2025

LYCEUM: learning to call copy number variants on low-coverage ancient genomes.

MOTIVATION: Copy number variants (CNVs) are pivotal in driving phenotypic variation that facilitates species adaptation. They are significant contributors to various disorders, making ancient genomes crucial for uncovering the genetic origins of disease susceptibility across populations. However, detecting CNVs in ancient DNA (aDNA) samples poses substantial challenges due to several factors: (i) aDNA is often highly degraded; (ii) contamination from microbial DNA and DNA from closely related species introduces additional noise into sequencing data; and finally, (iii) the typically low-coverage of aDNA renders accurate CNV detection particularly difficult. Conventional CNV calling algorithms, which are optimized for high-coverage read-depth signals, underperform under such conditions. RESULTS: To address these limitations, we introduce LYCEUM, the first machine learning-based CNV caller for aDNA. To overcome challenges related to data quality and scarcity, we employ a two-step training strategy. First, the model is pre-trained on whole genome sequencing data from the 1000 Genomes Project, teaching it CNV-calling capabilities similar to conventional methods. Next, the model is fine-tuned using high-confidence CNV calls derived from only a few existing high-coverage aDNA samples. During this stage, the model adapts to making CNV calls based on the downsampled read depth signals of the same aDNA samples. LYCEUM achieves accurate detection of CNVs even in typically low-coverage ancient genomes. We also observe that the segmental deletion calls made by LYCEUM show correlation with the demographic history of the samples and exhibit patterns of negative selection inline with natural selection. AVAILABILITY AND IMPLEMENTATION: LYCEUM is available at https://github.com/ciceklab/LYCEUM.

DNA Copy Number Variations↗

PubMed2026

Genomic insights into preantibiotic osteomyelitis pathogens and their link to current resistant hospital strains.

OBJECTIVES: Osteomyelitis is a severe bone infection that was frequently fatal before the introduction of antibiotics and remains a significant healthcare burden today. Staphylococcus aureus is the most common cause, alongside other hospital-acquired pathogens. Despite their clinical importance, the evolutionary history of these bacteria remains poorly understood. We investigated historical osteomyelitis specimens to identify causative pathogens and characterise their genomes, virulence and antimicrobial resistance (AMR). METHODS: Seven osteomyelitis-affected bones from adults dating to 19th-20th century Germany were analysed using ancient DNA (aDNA) approaches. After sequencing and screening, candidate pathogens were prioritised based on authentic aDNA damage patterns, established association with osteomyelitis and exclusion as environmental contaminants. Identified species were characterised by phylogenetics, multilocus sequence typing and virulence/AMR profiling. RESULTS: In four patients, we detected authentic aDNA from Acinetobacter baumannii, S. aureus or Streptococcus pyogenes. Detected taxa in the remaining three patients did not fulfil the criteria for further analysis. Two patients carried A. baumannii genomes clustering closely with modern avian and freshwater isolates. Both harboured virulence genes, alongside intrinsic efflux pumps and β-lactamases. One patient carried an S. aureus strain belonging to the globally disseminated clonal complex 30, responsible for outbreaks since the 1950s. Molecular dating indicated that this strain diverged from the wider lineage around 1800, placing it among the earliest members of this group. It encoded multiple virulence genes, but no methicillin resistance genes. The fourth patient carried an S. pyogenes strain related to modern epidemic lineages from North America, encoding conserved virulence factors, but no AMR genes. CONCLUSIONS: These specimens provide a window into the evolution of osteomyelitis pathogens. Although modern developments such as widespread antibiotic use have intensified the global resistance crisis, our findings indicate that the genetic foundations for pathogenicity and resistance were already present more than 100 years ago.

Ancient DNA↗

PubMed2026

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with systemic lupus erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within IRF7. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA-binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in interferon-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of the corresponding risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits.

ancient DNA↗

PubMed2026

Eastern origin and three-millennia persistence of a founding grapevine lineage in Iberian viticulture.

Viticulture became central to most Mediterranean civilizations a few millennia after the grapevine (Vitis vinifera L.) was domesticated in the South Caucasus/Near East. To elucidate the origins of the grapevines that enabled this westward spread over the past 3,000 years, we analyzed 28 grapevine seeds from seven archaeological sites in the Iberian Peninsula and Sardinia. Ancient DNA recovered from the oldest seeds with domesticated-like morphology (from ∼1,000 BCE), found in southwestern Spain, revealed nuclear and chloroplast genome signatures of Eastern Mediterranean cultivars. Seeds from the same and later Iron Age Iberian sites, however, showed genomic signatures suggesting hybridization between local wild grapevines and eastern-origin cultivars. The genetic makeup of Sardinian and northeastern Spanish seeds supports that local diversification giving rise to the Central European and Iberian wine genetic lineages had already occurred in the early Iron Age. In Iberia, Roman-period seeds were first-degree related to both the earliest eastern-introduced domesticates and a Medieval seed whose genetic makeup matches the extant Iberian variety "Pasa Valenciana." Another Medieval seed was inferred as an offspring of the extant "Heben," indicating that this major founder of Iberian germplasm has been continuously propagated for over 1,100 years. Our results confirm previous evolutionary models indicating that Western Mediterranean viticulture began with introductions of eastern domesticated grapevines, followed by early hybridization with local Iberian wild grapevines that may have facilitated viticulture adaptation to the new environment. The aDNA unveils that these introductions gave rise to extant cultivars through only a few sexual generations and long-term reliance on clonal propagation.

Iberian Peninsula↗

PubMed2026

Genomics and social practices at Mogou and other Gansu sites during prehistoric trans-Eurasian exchange.

Beginning approximately 4,000 years ago, southwest-Asian-originating domesticated crops and livestock began appearing in Gansu, a key crossroads in northwestern China, yet the population dynamics and social practices underlying these historically transformative events in the region have not been fully explored. Despite the adoption of western domesticates, genome sequences of 149 individuals from the large Mogou cemetery and ten other sites in Gansu, dating between 4,700 and 3,000 years ago, revealed migrations within East Asian regions but no detectable evidence of genetic influence from western or central Eurasia, suggesting that early agricultural dispersals may have followed a model distinct from that documented in Europe and Central Asia. The Mogou cemetery represents a continuous community that interacted with surrounding regions but does not exhibit clear matrilocal or patrilocal residential patterns. We found no strong evidence that co-buried individuals represented biological relatives. Non-local ancestry appears to be linked to lower-status burial practices.

Humans↗

PubMed2026

Local ancestry inference identifies robust evidence of selection in Neolithic Europe.

During the European Neolithic, migrating Anatolian farmers admixed with local hunter-gatherers, coinciding with major shifts in diet, environment, and lifestyle that imposed strong selective pressures. Local ancestry inference is widely used to detect selection following admixture, but most methods were developed and validated on present-day populations. Their performance in ancient DNA - where reference panels are smaller, data are sparser, and admixture is more ancient - remains unresolved. We benchmark eight local ancestry inference methods on 176 imputed Neolithic genomes. While individual-level ancestry estimates are highly correlated across methods, inferred tract lengths and admixture time estimates vary by an order of magnitude. Overall, we recommend Gnomix or RFMix for general use. We also investigated our ability to detect natural selection using LAI. Integrating results across methods and replicating across methods and in two independent datasets (n=378 and 1,121) we identify a robust ancestry deviation at FADS1/2, consistent with adaptation on metabolism. We also identify IRAK4 (innate immunity) as a candidate locus, but with less consistent signal across methods. Finally, we replicate previous reports of excess hunter-gatherer ancestry at the HLA, but these results are inconsistent across methods and suggest that they may be affected by bias in local ancestry inference. Our findings demonstrate that while local ancestry inference recovers biologically meaningful signals in ancient genomes, results can be sensitive to the methods used for inference, particularly in complex regions like the HLA. Method choice critically influences inferred ancestry patterns and selection signals, underscoring the importance of multi-method validation.

Journal Article↗

PubMed2026

COSIGT: population-scalable genotyping of complex loci from low-coverage sequencing data using pangenome graphs.

Pangenome graphs capture extensive structural diversity, but resolving complex loci from shallow sequencing remains challenging, particularly when samples are of low quality such as in ancient DNA. We introduce COSIGT (COsine SImilarity-based GenoTyper), which assigns diploid genotypes by matching read-depth distributions to haplotype paths via cosine similarity. Because this metric evaluates relative coverage profiles rather than absolute read counts, COSIGT substantially outperforms existing likelihood-based tools at low coverage (1-2X). We demonstrate scalability to thousands of modern and ancient genomes, enabling robust, population-scale analyses of complex variation directly from low-coverage datasets.

Humans↗

PubMed2026

Tracing the evolution and diversity of human parvovirus B19 across human history.

Human parvovirus B19 (B19V) is an ubiquitously spread, exclusively human pathogen, mainly posing risks to children, as well as pregnant and immunocompromised individuals. Despite evidence of B19V infection of human populations as far back as 7,000 years, the evolutionary history of B19V remains poorly understood. In this study, we present B19V genomic data from the remains of 53 globally distributed individuals spanning more than 8,000 years, including 7 children. Our findings suggest that the most recent common ancestor of all present B19V lineages existed around 12,000 years ago, at the end of the last Ice Age. Additionally, we identified an extinct Eurasian clade that participated in the recombination event that led to the emergence of B19V genotype 2 (GT-2). We date this event to ∼3,200-1,800 BP, potentially in the greater Mediterranean area. Our study shows aspects of how ancient parvovirus variants arose, disseminated, and impacted human health through time.

ancient DNA↗

PubMed2026

Evolutionary history of Aotearoa New Zealand's extinct mātuhituhi | bush wren.

The reconstruction of ecosystem responses to past climate change has historically focused on large vertebrates. In contrast, small vertebrates with potentially stricter habitat preferences have been neglected in ancient DNA studies despite their potential utility as proxies for inferring geographic and temporal changes in habitat. Aotearoa New Zealand's acanthisittid wrens are a speciose group of tiny perching birds, including the mātuhituhi | bush wren (Xenicus longipes ssp.). Despite its relatively recent extinction in the 1970s, very little is known about this enigmatic bird. Here we sequence mitochondrial genomes and nuclear ultra conserved genomic elements from 32 historical bush wren specimens to reconstruct their evolutionary history. We also genetically sex specimens and reanalyse their plumage to reconstruct aspects of bush wren plumage variation. Our analyses suggest North and South Island bush wren populations diverged 2.6 million years ago when narrowing and closure of Plio-Pleistocene seaways allowed colonisation of new habitats, followed by rapid glaciation-driven diversification of South Island populations 470,000-94,000 years ago. Genetic sexing allowed an accurate reconstruction of ontogenetic, sexual, and geographic variation in plumage. Our multidisciplinary data supports recognition of North and South Island populations as separate species, and the description of a new subspecies X. longipes perditus subsp. nov. This research shows how ecosystems can buffer against the impacts of climate change up to an ecological tipping point, which has important lessons for conservation management in a fast-changing world.

Acanthisittidae↗

PubMed2026

Appreciating diversity: a review of the Iranian genomic landscape.

Understanding population structure is crucial for designing and interpreting human genetic studies. This is of particular importance for Iran as a large, ethnically diverse country whose population has often been treated as a genetically homogenous entity. Here, we synthesize published literature on the genetic structure of the Iranian population. We further complement this by recapitulating the geographic, historic, and ethnic background, by comparisons with neighboring countries, and by reviewing autozygosity in Iran. This synthesis confirms large genetic diversity, likely building upon an autochthonous component that was reshaped by multiple migrations. The substantial autosomal substructure falls apart into groups of largely shared genetic ancestry (Central Iranian Cluster) and those with substantial admixture in the past. Structure with respect to uniparental markers is less pronounced. We also find consistency for generally high but varying levels of autozygosity, influenced by ethnicity, residence, and socioeconomic factors. Finally, we recapitulate some examples for geographical differences in disease prevalence and (founder) mutation carrier frequency. Our synthesis emphasizes the need to account for this diversity in human genetic studies in the Iranian population. We provide conclusions for the design of such studies and state expectations on the transferability of genetic findings and genomic predictions, such as polygenic scores, within Iran as well as to neighboring countries. Iran's diversity and geographic location provide renewed motivation for conducting population genetic and ancient DNA studies as well as providing genomic reference resources in this part of the world.

Journal Article↗

PubMed2026

Genomic insights into natural selection in recent human history.

For over a century, scientists have debated the extent to which genetic and phenotypic variation among present-day humans is the result of natural selection - in which heritable traits influence survival or reproduction - versus neutral processes such as genetic drift or population history. The initial sequencing of the human genome and subsequent population resequencing studies enabled genome-scale searches for signatures of selection in present-day genomes. This first generation of genome-wide selection scans identified many targets but left open questions about the timing and nature of selection, making it challenging to identify environmental and biological drivers. Recent methodological advances based on reconstructing ancestral recombination graphs have increased the potential power and resolution of selection scans based on present-day genomes, while the availability of new data on ancient DNA has facilitated the direct reconstruction of genetic change through time. However, there is little consensus on how to use these data to detect and interpret signatures of selection, while avoiding confounders. Here, we review the current state of knowledge about the impact of selection on human genomic diversity and highlight conceptual advances in our understanding of human evolution over the past 10,000 years.

Journal Article↗

PubMed2026

What Uniparental Lineages Tell Us About the Prehistoric Human Colonization of the Americas.

OBJECTIVES: From the perspective of uniparental markers, the view of the human prehistoric settlement of America is that it resulted from a single main migration after the Last Glacial Maximum, following a long or short period of genetic isolation in Beringia. Ancient DNA and whole genome analyses have confirmed this view. My objective here is to demonstrate that humans entered America before the LGM and that the documented post-LGM expansions began in South instead of North America. METHODS: In this work, I have reanalyzed all publicly available mitochondrial DNA and Y-chromosome haplogroups in the American population using simple phylogenetic and phylogeographic methodologies. RESULTS: The arrival of the American settlers occurred more than 30,000 years ago, preceding the LGM. As genomic studies have uncovered, at least two Asian populations contributed to the ancestry of the immigrant population. Low population density and climatic deterioration led to a long period of demographic eclipse, during which small bands of hunter-gatherers made long journeys in search of favorable niches. After the LGM, the climate improved, and demographic expansions occurred in multiple independent centers. The founding and expansion ages of the uniparental haplogroups indicate that these centers were in South America, particularly the Colombian isthmus, the Andean region, the Southern Cone, and the Amazon. Subsequent dispersals occurred in North America, one involving mitochondrial haplogroups A2, C1, and D1, but not B2, and another, of lesser magnitude, represented by the expansion of haplogroups C4c and X2a. CONCLUSION: This work offers a previously unexplored model for the colonization of the Americas.

Native American↗

PubMed2026

A highly prevalent lupus risk haplotype increases IRF7-dependent induction of IFN-α, enhancing antiviral defense and exacerbating autoimmunity.

UNLABELLED: Genome-wide association studies have identified genetic polymorphisms at 11p15 associated with Systemic Lupus Erythematosus (lupus). Statistical fine mapping prioritizes a highly prevalent coding haplotype within the IRF7 gene. Analysis of ancient DNA confirms that this haplotype has persisted at high frequencies in the global population for millennia. The IRF7 risk haplotype is sufficient to increase nuclear localization of IRF7 and transcriptional activity downstream of pattern recognition receptor pathways. This risk haplotype increases IRF7 DNA binding strength and alters IRF7 DNA sequence specificity, resulting in genotype-dependent increases in IFN-α production in numerous biological systems, including monocytes and airway epithelial cells. CRISPR engineering of a homologous risk variant in mouse Irf7 results in both enhanced innate control of virus infection and increased autoantibody titers in a model of autoimmunity. Altogether, we establish a persistent and prominent genetic IRF7 haplotype that amplifies IRF7 activity in a manner that has immunological risks and benefits. HIGHLIGHTS: Genetic analysis using modern and evolutionary datasets identifies a persistent and highly prevalent lupus-associated coding haplotype in IRF7 at 11p15 The IRF7 lupus risk haplotype increases IFN-α production by monocytes and airway epithelial cells The IRF7 lupus risk haplotype increases IRF7 DNA binding strength and alters DNA sequence specificity A homologous lupus risk variant in mouse Irf7 enhances control of vesicular stomatitis virus and exacerbates autoantibody production.

Journal Article↗

PubMed2026

Two blind spots in the demographic inference of human origins from genomic data.

Ancient DNA and new inference methods have transformed the study of human origins, but consensus has not followed. Evidence increasingly indicates that hominin populations were pervasively structured and admixed, so complexity rather than simplicity is the appropriate prior. Here I highlight two blind spots that impede resolving that complexity. First, every inference passes through summaries of the data, and those summaries bound what can be recovered. Second, the space of candidate models is vast, yet competing model classes are rarely fit to common data, so a reported best model carries little evidence about untested model classes. This second blind spot reflects practice rather than data. It can be narrowed by testing competing models against withheld summaries and by reporting the models that were tried and rejected rather than only the winner.

Journal Article↗

PubMed2026

Ancestry, admixture, and pathogens in contemporaneous Neolithic farmers and foragers on the Island of Gotland.

Two archaeological cultural complexes; the Neolithic Funnelbeaker culture (FBC) and the Pitted ware culture (PWC), coexisted on Gotland for over 500 years, between ~3300 and 2800 calBCE. The ancestry of the FBC farmers and PWC marine foragers largely aligns with European Neolithic Farmers and European Mesolithic foragers, respectively, but the direct interactions between the groups on Gotland is not understood. We present a Middle Neolithic (MN) high-coverage genome and a Late Neolithic (LN) low-coverage genome from the Ansarve FBC dolmen. We investigate ancestry, admixture, and pathogens among these MN farmers (n = 6), foragers (n = 19), and the LN individual. We find that recent gene-flow between farmers and foragers could have taken place, although most gene-flow happened prior to their coexistence on the island. We also find evidence of different Yersinia pestis strains in the three cultural groups, showing that the pestis was widespread among groups with different subsistence strategies.

Humans↗

PubMed2026

Population genomics, demography, and circum-Baltic connectivity of Early Medieval southwestern Finland.

BACKGROUND: Knowledge of Early Medieval Finland (1050-1250 CE) relies primarily on archaeological evidence, as contemporary sources are scarce. The available evidence indicates two distinct cultural-economic zones: coastal and inland. Using newly generated genomic data from 34 ancient individuals alongside modern Finnish genomes, we characterise Late Iron Age and Early Medieval ancestry in southwestern Finland, reconstruct demographic patterns, and place individuals within a circum-Baltic relatedness network. RESULTS: Early Medieval ancestry in inland southwestern Finland was very similar to that of present-day inhabitants. Ancient coastal and inland individuals were genetically indistinguishable, whereas modern coastal populations showed substantially more Scandinavian ancestry, and less Baltic ancestry compared to their ancient counterparts. IBD (identity-by-descent) analyses also indicate a major genetic shift in the coastal zone since the Early Medieval Period. Effective population size increased throughout the study period and was ~ 13,000 by 1250 CE. IBD links between Scandinavia and Early Medieval Finland align with known archaeological connections. Furthermore, we identify IBD links between individuals from Early Medieval Finland and victims of the Kronan warship sinking. CONCLUSIONS: We demonstrate nearly a millenium of population continuity in the inland zone of southwestern Finland, contrasted by a large, contemporaneous genetic shift in the coastal zone. This ancestry shift corresponds with documented medieval emigration from Sweden to Finland. The regional population rapidly expanded during this time period, likely due to new agricultural practices and favourable climatic conditions. Our circum-Baltic IBD network indicates that southwestern Finland was firmly embedded into the wider, pre-modern Baltic world.

Humans↗

PubMed2024

Advancing responsible genomic analyses of ancient mollusc shells.

The analysis of the DNA entrapped in ancient shells of molluscs has the potential to shed light on the evolution and ecology of this very diverse phylum. Ancient genomics could help reconstruct the responses of molluscs to past climate change, pollution, and human subsistence practices at unprecedented temporal resolutions. Applications are however still in their infancy, partly due to our limited knowledge of DNA preservation in calcium carbonate shells and the need for optimized methods for responsible genomic data generation. To improve ancient shell genomic analyses, we applied high-throughput DNA sequencing to 27 Mytilus mussel shells dated to ~111-6500 years Before Present, and investigated the impact, on DNA recovery, of shell imaging, DNA extraction protocols and shell sub-sampling strategies. First, we detected no quantitative or qualitative deleterious effect of micro-computed tomography for recording shell 3D morphological information prior to sub-sampling. Then, we showed that double-digestion and bleach treatment of shell powder prior to silica-based DNA extraction improves shell DNA recovery, also suggesting that DNA is protected in preservation niches within ancient shells. Finally, all layers that compose Mytilus shells, i.e., the nacreous (aragonite) and prismatic (calcite) carbonate layers, with or without the outer organic layer (periostracum) proved to be valuable DNA reservoirs, with aragonite appearing as the best substrate for genomic analyses. Our work contributes to the understanding of long-term molecular preservation in biominerals and we anticipate that resulting recommendations will be helpful for future efficient and responsible genomic analyses of ancient mollusc shells.

Animals↗

PubMed1979

Non-repetitive DNA sequence divergence in phylogenetically diploid and tetraploid teleostean species of the family cyprinidae and the order isospondyli.

Non-repetitive DNA of anciently tetraploid teleostean species was analysed for the presence of duplicated sequences. Closely related diploid species were investigated in comparison. From the reassociation kinetics of total nuclear DNA, rate constants and fraction sizes of classes of repetitive and non-repetitive sequences were determined. DNA fractions enriched in the slowest renaturing sequence class were determined. DNA fractions enriched in the slowest renaturing sequence class were prepared and subjected to reassociation. The rate constants of these reactions were compared with the values expected for single-copy DNA from analytical genome size determinations. From reassociated DNA enriched in non-repetitive sequences also the melting temperatures were determined as a measure of internal base sequence heterogeneity. It has been shown that the two ancient tetraploids Cyprinus carpio and Thymallus thymallus are, with regard to the thermal stability of reassociated non-repetitive DNA, and with regard to the correspondence of reaction rates with the values expected for single copy DNA, indistinguishable from diploid controls (Rutilus rutilus, Clupea harengus and Sprattus sprattus). The tetraploid species Salmo irideus, Salvelinus fontinalis and Coregonus lavaretus appear as very recent tetraploids with regard to these criteria. The significance of the results for estimating the time of occurrence of polyploidisation events in these taxa is discussed.

Animals↗