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Kristiansen, K.

Publications and source records attributed to Kristiansen, K..

At least 19 recordsLinked to original sources

Migrations facilitated the cultural diffusion of megaliths in Neolithic Europe

Around 6700 BP (years before present), Neolithic Europe saw the emergence of megalithic monuments in northern France, followed by a rapid spread to the rest of the continent1. However, whether this was driven by the transmission of ideas (cultural diffusion) or the movement of people remains debated. To test whether this spread coincided with population movements, we reconstructed the population history of the European Neolithic ([~]6500-4800 BP) by analysing genomic data from 2963 ancient individuals, including 46 unpublished genomes from megalithic and related contexts. To assess the alternative scenario whereby megaliths spread through contact networks, as expected under cultural diffusion, we integrated archaeological evidence with radiocarbon chronologies to reconstruct past trading networks. We identify northern France, where megaliths first emerged, as a zone of genetic admixture and cultural influence from the two major early Neolithic divisions: the Cardial of the Western Mediterranean and the Linear Pottery traditions of central Europe. From this admixed population, we uncover several migrations associated with the formation of the Funnel Beaker Culture in north-central Europe and the neolithisation of Scandinavia and the British Isles. We find that megaliths were spread exclusively within regions impacted by Cardial-related genetic ancestry, but only in the British Isles and Ireland did their emergence coincide with the time of the migration. The temporal delay between the migrations and the spread of megaliths elsewhere reveals that neither population movements nor cultural diffusion alone fully explains the geospatial distribution of the megalithic tradition. Rather, megaliths diffused across different Neolithic groups whose long-distance trade networks formed in the wake of earlier population movements. Our findings highlight the need to move beyond simplistic interpretations that present migrations or cultural diffusion as isolated events bringing technological and cultural innovations.

evolutionary biology↗

Complete genome-derived metabolic interactions reveal impact of gut ecology on human health

Metabolic interactions govern gut microbiome assembly, yet functional rules remain obscured by genomic incompleteness and fragmentation. Here, we leverage 1,150 complete genomes to construct genome-scale metabolic models, demonstrating that draft genomes introduce systemic artifacts missing critical transport functions. We observe that metabolic interactions are intrinsically driven by genomic traits and niche specialization rather than random association. We stratifies strains into four ecological groups, including active players, resource predators, utilizers, and contributors, each of which exhibits distinct metabolite exchange/competition signatures. This functional architecture is strongly coupled to secondary metabolism. Applying this framework to inflammatory bowel disease revealed distinct temporal dynamics of ecological groups across disease subtypes, where group-specific dysbiosis predicted clinical phenotypes better than whole community profiles. Furthermore, integrating metabolic and co-occurrence networks to identify keystone for classifiers as features significantly improved disease diagnosis. Our study provides novel insights into gut metabolic interaction landscape, bridging the gap between genomic potential and clinical utility for precision microbiome therapeutics.

microbiology↗

Complete Genomes of Cultivated Gut Bacteria Reveal Mobile Genetic Element-Driven Functional Diversity with Therapeutic Implications

Cultivated bacterial isolates are essential for elucidating gut microbiota functions, yet reliance on fragmented draft genomes and limited mobile genetic element (MGE) annotation has constrained high-resolution analyses. Here, we present the Cultivated Complete Genome Reference (CCGR), a comprehensive compendium of 1,150 fully circularized human gut bacterial genomes. Overcoming draft limitations, CCGR achieves chromosome-scale resolution and reveals distinct evolutionary strategies shaping gene topological organization in response to bacterial growth. Furthermore, we decode the dynamic landscape of MGEs, demonstrating that broad-host-range phages follow strict positional patterns by integrating at conserved chromosomal hotspots flanked by nutrient transporter loci. Importantly, we provide mechanistic in vivo evidence that accessory genomic elements drive strain-level functional heterogeneity. Specifically, the plasmid-encoded scrK gene in Levilactobacillus brevis involved in fructose catabolism is required to mitigate fructose-diet-exacerbated colitis. Collectively, CCGR establishes a framework linking chromosomal architecture and MGEs to bacterial evolution and host health, enabling precise, strain-resolved functional investigations.

microbiology↗

Towards molecular-based functional classification of fetal bovine serum

Quality and price of fetal bovine serum (FBS) are traditionally determined by geographical origin and parameters listed in the Certificate of Analysis (CoA). Despite its central role in cell culture, selecting suitable FBS batches remains costly and labor-intensive due to substantial batch-to-batch variation. We propose a molecular assessment strategy based on transcriptomic and cytokine profiling of cells cultured in different FBS batches to evaluate performance more reliably. Analysis of differential gene expression in three cell lines - MRC-5, Jurkat, and THP-1 - enables batch grouping and reveals pathway-specific effects, with immune-related pathways showing the most pronounced variability. Although CoA parameters can stratify batches by origin, they do not consistently correlate with cytokine secretion or gene expression across cell lines. These findings demonstrate that geographical origin is an inadequate predictor of functional FBS performance and that molecular profiling provides a more robust and informative assessment.

molecular biology↗

Dual human milk oligosaccharide-fibre utilisation drives gut microbiome selection during weaning

Gut microbiome (GM) maturation in early life follows organised taxonomic successions. How weaning impacts these trajectories remains underexplored. Here, we sampled faeces from seven mother-infant dyads at pre-, early and late weaning. Enrichment cultures (n=306) and metagenomic (n=108) analyses revealed an unexpected prevalence of fibre degradation genes and the growth of the pre-weaning infant GM on common dietary fibres. Utilisation of both human milk oligosaccharides (HMOs) and dietary fibres was revealed as a metabolic hallmark of the weaning GM. We showed that HMO-utilisation is retained beyond weaning, by analyses of maternal GM and HMO utilisation in 137 maternal isolates. Our findings highlight dual HMO-dietary fibre utilisation as a hitherto unrecognised driver that potentially orchestrates the selection of distinct adult GM species during weaning. This work outlines a plausible mechanism underlying the organised GM maturation in early life and highlights a previously overlooked role of HMOs during the weaning transition.

microbiology↗

Improving archaeological metadata reporting in human paleogenomicstudies

Paleogenomic research has dramatically increased our understanding of past demographic and adaptive processes, but has also been criticized for a perceived disconnect between geneticists and other parties involved in the study of the past. For interdisciplinary research to be productive, contextual metadata associated with paleogenomic samples should be accessible in the same publication. Here, we conduct a pilot study examining the extent of archaeological metadata reporting in 30 peer-reviewed human paleogenomic studies, based on genetic sequences from 3911 ancient humans predominately from Western Eurasia, published between 2013 and 2024. We show inconsistent reporting of archaeological data across studies, and have sought to identify the driving factors. Overall, we found no strong explanatory variables, though some metadata fields - like Geolocation - have improved in completeness over time. These inconsistencies mean that metadata reporting is often insufficient to directly investigate the relationship between patterns of cultural and genetic change on the basis of published data alone. We propose a minimum information checklist as a best-practice guideline for collecting and reporting archaeological data in the future.

genomics↗

Tracing the Spread of Celtic Languages using Ancient Genomics

Celtic languages, including Irish, Scottish Gaelic, Welsh and Breton, are today restricted to the Northern European Atlantic seaboard. However, between three and two thousand years before present (BP), Celtic was widely spoken across most of Europe before being largely replaced by Germanic, Latin or Slavic1-4. Despite this rich history, how Celtic spread across the European continent remains contentious5. The debate is currently focused around three main models based on historical linguistics and archaeology: (1) a Late Bronze Age/Early Iron Age spread from Central Europe associated with the Hallstatt and La Tene Cultures6-9; (2) a Late Neolithic/Early Bronze Age spread along the Atlantic seaboard linked to the Bell Beaker Culture10-13; and (3) a Bronze Age spread from France, Iberia or Northern Italy14-16. Previous genomic investigations are centred around the arrival of Celtic to specific regions: Britain17, Iberia18 and Southwestern Germany19. Here, we utilise new genomic data from Bronze and Iron Age Europe to test how the population histories align with the three models of prehistoric spread of the Celtic languages. In line with the theory that Celtic spread from Central Europe during the Late Bronze Age to Early Iron Age, we find Urnfield-related ancestry - specifically linked to the Knoviz subgroup to have formed between 4 and 3.2 kyr BP, and subsequently expanded across much of Western Europe between 3.2 and 2.8 kyr BP. This ancestry further persisted into the Hallstatt Culture of France, Germany and Austria, impacting Britain by 2.8 kyr BP and Iberia by 2.5 kyr BP. Our findings thus agree with the model of Central European spread of the Celtic languages through consecutive expansions of the Urnfield, Hallstatt and La Tene Cultures rather than the competing models. These results demonstrate, yet again, the power of ancient population genomics in addressing long-standing debates in historical linguistics and archaeology.

evolutionary biology↗

PepGo: a deep learning and tree search-based model for de novo peptide sequencing

Identifying peptide sequences from tandem mass spectra is a fundamental problem in proteomics. Unlike search-based methods that rely on matching spectra to databases, de novo peptide sequencing determines peptides directly from mass spectra without any prior information. However, the design of models and algorithms for de novo peptide sequencing remains a challenge. Many de novo approaches leverage deep learning but primarily focus on the architecture of neural networks, paying less attention to search algorithms. We introduce PepGo, a de novo peptide sequencing model that integrates Transformer neural networks with Monte Carlo Tree Search (MCTS). PepGo predicts peptide sequences directly from mass spectra without databases, even without prior training. We show that PepGo surpasses existing methods, achieving state-of-the-art performance. To our knowledge, this is the first approach to combine deep learning with MCTS for de novo peptide sequencing, offering a powerful and adaptable solution for peptide identification in proteomics research.

bioinformatics↗

Spatial dissimilarity analysis in single cell transcriptomics

The spatial dissimilarity method is a new statistical tool to uncover complex bivariate relationships in single cells and spatial transcriptomics data, thereby addressing unresolved issues such as alternative splicing and allele-specific gene expression. By applying our spatial dissimilarity analysis method on datasets of neurons, tumor, and normal cells, we identified thousands of alternatively spliced genes and instances of allele-specific gene expression. This is particularly evident in the analysis of quiescent and transitioning cell states, where our method reveals the nuanced gene expression dynamics associated with these states. Notably, our findings highlight how allele-specific genetic variants can provide insights into the subclone architecture of normal cells and cancer cells, offering a more comprehensive understanding of cellular heterogeneity and a new insight to understand gene function at specific cell types. The spatial dissimilarity analysis method deepens our comprehension of cellular complexity and gene expression dynamics during cell state transitions.

bioinformatics↗

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↗

Host-gut microbiota interactions shape parasite infections in farmed Atlantic salmon

Animals and their associated microbiota share long evolutionary histories. Both host genotype and associated microbiota influence phenotypes such as growth and disease resilience. We applied a hologenomic approach to explore the relationship between host and microbiota in shaping lifetime growth and parasitic cestode infection in farmed Atlantic salmon. Genomes, transcriptomes, metabolomes and metagenomes were generated from the guts of 460 harvest-aged salmon, 82% of which were naturally infected with an intestinal cestode. One salmonid-specific Mycoplasma dominated the gut microbiota of uninfected salmon. However, the microbiota was perturbed in smaller, parasitised fish, with increased abundance of Vibrionaceae and other Mycoplasma species previously linked to the cestode microbiota. The cestode-associated Mycoplasma carry more virulence-associated genes than the salmonid Mycoplasma. Colonisation by one cestode-associated Mycoplasma was associated with a region of the salmon genome encoding several long noncoding RNA genes previously associated with host control of intestinal microbiota. Integrating the multiple omic datasets revealed coordinated changes in the salmon gut transcriptome and metabolome that correlated with shifts in the microbiota of smaller, parasitised fish. Our results suggest that cestode infections introduce new microbes and trigger host responses, altering the gut microbiota with increases in potentially pathogenic microbes. Establishment of these microbes is partially shaped by the genetic background of the host. Our study highlights the value of a hologenomic approach for gaining an in-depth understanding of trilateral interactions among host, microbiota and parasite.

systems biology↗

Specific gut pathobionts escape antibody coating and are enriched during flares in patients with severe Crohn's disease

Patients with Crohns disease (CD) exhibit great heterogeneity in disease presentation and treatment responses, where distinct gut microbiota-host interplays may play part in the yet unresolved disease etiology. We here characterized absolute and relative single and multi-coating of gut bacteria with immunoglobulin (Ig)A, IgG1, IgG2, IgG3 and IgG4 in CD patients and healthy controls. Patients with severe disease exhibited distinctly higher gut bacterial IgG2-coating. IgG2-coated bacteria included both known pathogenic and non-pathogenic bacteria that co-existed in communities with two non-coated gut pathobionts Campylobacter and Mannheimia. These latter two exhibited low prevalence, rarely coincided, and were strongly enriched during disease flares in CD patients across independent and geographically distant cohorts. Since antibody-coating of gut pathobionts diminishes epithelial invasion and inflammatory processes, escape from coating by specific gut pathobionts may be a mechanism related to disease flares in the subgroup of CD patients with severe disease.

immunology↗

Altitude-dependent agro-ecologies impact the microbiome diversity of scavenging indigenous chicken in Ethiopia

Scavenging indigenous village chickens play a vital role in sub-Saharan Africa, sustaining the livelihood of millions of farmers. These chickens are exposed to vastly different environments and feeds compared to commercial chickens. In this study, we analysed the caecal microbiota of 243 Ethiopian village chickens living in different altitude-dependent agro-ecologies. Differences in bacterial diversity were significantly correlated with differences in specific climate factors, topsoil characteristics, and supplemental diets provided by farmers. Microbiota clustered into 3 enterotypes, with one particularly enriched at high altitudes. We assembled 9,977 taxonomically and functionally diverse metagenome-assembled genomes, the vast majority of which were not found in a dataset of previously published chicken microbes, or in the Genome Taxonomy Database. The wide functional and taxonomic diversity of these microbes highlights their importance in the local adaptation of indigenous poultry, and the significant impacts of environmental factors on the microbiota argues for further discoveries in other agro-ecologies.

microbiology↗

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↗

The Selection Landscape and Genetic Legacy of Ancient Eurasians

The Holocene (beginning [~]12,000 years ago) encompassed some of the most significant changes in human evolution, with far-reaching consequences for the dietary, physical, and mental health of present-day populations. Using a dataset of >1600 imputed ancient genomes 1, we modelled the selection landscape during the transition from hunting and gathering, to farming and pastoralism across West Eurasia. We identify major selection signals related to metabolism, including that selection at the FADS cluster began earlier than previously reported, and that selection near the LCT locus predates the emergence of the lactase persistence allele by thousands of years. We also find strong selection in the HLA region, possibly due to increased exposure to pathogens during the Bronze Age. Using ancient individuals to infer local ancestry tracts in >400,000 samples from the UK Biobank, we identify widespread differences in the distribution of Mesolithic, Neolithic, and Bronze Age ancestries across Eurasia. By calculating ancestry-specific polygenic risk scores, we show that height differences between Northern and Southern Europe are associated with differential Steppe ancestry, rather than selection, and that risk alleles for mood-related phenotypes are enriched for Neolithic farmer ancestry, while risk alleles for diabetes and Alzheimers disease are enriched for Western Hunter-gatherer ancestry. Our results suggest that ancient selection and migration were major contributors to the distribution of phenotypic diversity in present-day Europeans.

evolutionary biology↗

A Unified Catalog of 19,251 Non-human Reference Species Genomes Provides New Insights into the Mammalian Gut Microbiomes

The gut microbiota is essential for host health and survival. Here, using samples from animals living in the Qinghai-Tibetan Plateau, we recovered 119,568 metagenome-assembled genomes (MAGs) that were clustered into 19,251 species-level genome bins (SGBs) of which most represent novel species. We present a novel mechanism shaping mammalian gut microbiomes using ancestral founder bacteria (AFB) as a core skeleton and recurring lineage-specific gains of microbial species that are transferred frequently among multiple hosts, not strictly limited by host phylogeny. Such lineage specific gains are responsible for increasing gut microbial diversity, maintaining functional stability, and endowing specific functions for host adaptions. Our analyses did not support the existence of co-phylogeny or co-speciation events between mammal hosts and their individual gut symbionts. The results presented in this study not only reveal novel unique gut microbial species and offer insight of value for understanding the diversity, stability, functionality of the mammalian gut microbiomes, and the co-evolution with their hosts, but also emphasize that animals living in extreme environments are a promising resource for the discovery of novel biological functions.

microbiology↗

Effect of gastrointestinal alterations mimicking elderly conditions on in vitro digestion of meat and soy proteins

We evaluated the digestion of meat (chicken, beef, and pork) and soy proteins under in vitro conditions mimicking gastrointestinal (GI) conditions of adults (control, C) and elderly with achlorhydria (EA). The changes in degree of hydrolysis (DH), SDS-PAGE profiles, peptide concentration, and proteomics profiles during the digestion process were investigated. Digestion under the EA condition markedly decreased the DH of all protein sources, especially for soy protein. SDS-PAGE profiling and proteomics showed that myofibrillar/sarcoplasmic protein from meat and glycinin/beta-conglycinin from soy were the proteins most affected by the different digestive conditions. Our results indicated that the difference in the digestibility of meat protein between EA and control conditions gradually narrowed from the gastric to the intestinal phase, while a pronounced difference between control and EA conditions was maintained also in the intestinal phase. This work provides new insights of value for future dietary recommendations for elderly individuals.

biochemistry↗

Diversity, function and evolution of marine microbe genomes

Trillions of marine bacterial, archaeal and viral species contribute to the majority diversity of life on Earth. In the current study, we have done a comprehensive review of all the published studies of marine microbiome by re-analyzing most of the available high throughput sequencing data. We collected 17.59 Tb sequencing data from 8,165 metagenomic and prokaryotic samples, and systematically evaluated the genome characters, including genome size, GC content, phylogeny, and the functional and ecological roles of several typical phyla. A genome catalogue of 9,070 high quality genomes and a gene catalogue including 156,209,709 genes were constructed, representing the most integrate marine prokaryotic datasets till now. The genome size of Alphaproteobacteria and Actinobacteria was significant correlated to their GC content. A total of 44,322 biosynthetic gene clusters distributed in 53 types were detected from the reconstructed marine prokaryotic genome catalogue. Phylogenetic annotation of the 8,380 bacterial and 690 archaeal species revealed that most of the known bacterial phyla (99/111), including 62 classes and 181 orders, and four extra unclassified genomes from two candidate novel phyla were detected. In addition, taxonomically unclassified species represented a substantial fraction of 64.56% and 80.29% of the phylogenetic diversity of Bacteria and Archaea respectively. The genomic and ecological features of three groups of Cyanobacteria, luminous bacteria and methane-metabolizing archaea, including inhabitant preference, geolocation distribution and others were through discussed. Our database provides a comprehensive resource for marine microbiome, which would be a valuable reference for studies of marine life origination and evolution, ecology monitor and protection, bioactive compound development.

microbiology↗