Biology subjects

van der Valk, T.

Publications and source records attributed to van der Valk, T..

16 recordsLinked to original sources

bioRxiv2026

DNAharvester: A Nextflow Pipeline for Analysing Highly Degraded DNA from Ancient and Historical Specimens

Ancient DNA (aDNA) research has advanced rapidly with the development of high-throughput sequencing, enabling genome-wide analyses of large collections of prehistoric specimens. However, analysing palaeontological and archaeological material with highly degraded DNA constitutes a major bioinformatic challenge. DNA from such samples is characterised by short fragment lengths, low endogenous content, post-mortem damage, and cross-species contamination, which can increase spurious mapping and reference bias, affecting downstream population genetic inferences. We present DNAharvester, a modular and reproducible pipeline designed specifically for processing highly degraded DNA from ancient and historical specimens. DNAharvester integrates metagenomic filtering, competitive mapping, adaptive aligner selection (incorporating BWA-aln, BWA-mem, and Bowtie2), and systematic evaluation of reference bias and spurious mapping. By incorporating flexible mapping and filtering strategies, the pipeline can be adapted to varying sample preservation, focusing on maximising authentic data recovery. DNAharvester features subworkflows for iterative assembly of mitogenomes, identification of genomic repeats and CpG sites, taxonomic classification, microbial/pathogen screening, genetic sex determination, and variant calling. To accommodate varying sequencing depths, the pipeline supports diploid variant calling, genotype likelihood estimation, and pseudo-haploid random allele calling. Implemented in Nextflow, DNAharvester provides a highly scalable, containerised framework that enhances reproducibility, portability, and robustness in aDNA analyses. We validated the pipeline using simulated and empirical datasets, demonstrating its ability to systematically mitigate complex background contamination while preserving authentic genomic signals. By streamlining complex bioinformatic tasks through simple configuration files, DNAharvester establishes a standardised approach for analysing aDNA datasets and makes genomic analyses of ancient remains accessible to the broader research community.

bioinformatics↗

bioRxiv2026

Lifestyle impacts the oral microbiome of Classical and Post-classical societies in Italy

ObjectivesThe fall of the Roman Empire (476 CE) profoundly affected the lives of its peoples due to the political, administrative, and territorial changes that occurred. The majority of written records of the time focus on the social elite, leaving larger parts of the population understudied. Here, we employ a bioarchaeological approach to understand how differences in lifestyle may be reflected in the oral microbiome of people from different social classes living before and after the fall. Material and MethodsWe analysed shotgun sequencing data from dental calculus, the preserved oral microbiome, of 67 individuals belonging to different social classes from two Classical cemeteries dated to I-III century CE (Lucus Feroniae and Isola Sacra) and one post-Classical cemetery dated to IV-VIII century CE (Selvicciola), all located in proximity to the city of Rome, Italy. ResultsWe detect significant differences in the oral microbiome taxonomic and functional composition across time periods and social classes, with the rural town of Lucus Feroniae standing out compared to its two counterparts. Reliable identification of dietary items was not possible. DiscussionThe distinct oral microbiome of Lucus Feroniae could reflect differences in general health and subsistence practices. The rural position of this community may have mitigated the cyclical food crises that, instead, affected the contemporary Isola Sacra and the later community of Selvicciola, thereby buffering against the nutritional stress observed in these two locations.

genomics↗

bioRxiv2025

Genomic and Dietary Insights from Non-Invasive Sampling of Western Capercaillie in Tyresta National Park (Sweden)

The Western Capercaillie (Tetrao urogallus), a boreal forest specialist, has experienced marked declines in southern Sweden due to habitat loss, fragmentation, and isolation. Tyresta National Park and the surrounding forests harbors one of the regions last remnant southern populations, yet little is known about its genetic health, population structure, and dietary ecology. Here, we used low-coverage whole-genome sequencing of 273 non-invasively collected samples (feathers and faeces) to comprehensively assess the status of this population. Feather samples yielded high-quality genomic data, enabling sex identification, estimation of genome-wide heterozygosity, runs of homozygosity (ROH), and relatedness inference. Heterozygosity levels in Tyresta were comparable to other European Western Capercaillie populations, and inbreeding levels were generally low, although several individuals showed long ROH indicative of recent close-kin mating. Population structure analyses revealed a genetically distinct and panmictic unit with evidence of female-biased dispersal. Kinship analysis uncovered a highly interconnected social network, with males having on average more relatives than females. Recapture simulations based on genotype matching estimated a current maximum population size of 164 - 208 individuals. Faecal metagenomic analysis revealed a diverse diet, including key plant species such as blueberry, lingonberry and alder, and a wide range of invertebrates critical for chick development. Despite its current genetic robustness, the Tyresta population is small, isolated, and at risk of inbreeding depression. Conservation efforts should prioritize maintaining habitat quality, promoting gene flow, e.g. by protecting migration corridors to neighbouring populations and ensuring a rich forest invertebrate community to support population resilience.

ecology↗

bioRxiv2025

The Impact of Reference Genome Divergence on Ancient DNA Damage Detection in Metagenomic Contexts

The reliability of ancient DNA (aDNA) authentication depends on detecting characteristic damage patterns, particularly cytosine deamination at fragment ends. However, in ancient metagenomic studies, sequence divergence between aDNA reads and available reference genomes may obscure such damage signals. We systematically evaluated how reference genome divergence, read count, read length, and damage levels affect aDNA damage profiles using both empirical datasets and controlled simulations. Using ancient Yersinia pestis and Hepatitis B virus data, we show that mapping to divergent reference genomes significantly reduces the detectability and intensity of characteristic damage patterns, particularly at low read counts. Simulations further revealed that reference genome identity is the strongest predictor of damage intensity, while read count primarily influences damage stochasticity. We introduce a correction matrix that adjusts C-to-T damage profiles for reference divergence, improving damage signal recovery. Our findings highlight methodological considerations for authenticating aDNA in metagenomic contexts, particularly when closely related reference genomes are unavailable.

bioinformatics↗

bioRxiv2025

Disinfecting eukaryotic reference genomes to improve taxonomic inference from ancient environmental metagenomic data

Ancient environmental DNA is increasingly essential for reconstructing past ecosystems, particularly when palaeontological and archaeological tissue remains are absent. Detecting ancient plant and animal DNA in environmental samples often relies on using extensive eukaryotic reference genome databases for profiling shotgun metagenomics data. However, microbial contamination in these references can introduce substantial biases in taxonomic assignments, especially given the typical low abundance of plant and animal DNA in such samples. In this study, we present a method for identifying bacterial and archaeal-like sequences in eukaryotic genomes and apply it to nearly 3,000 reference genomes from NCBI RefSeq and GenBank (vertebrates, invertebrates, plants) as well as the 1,323 PhyloNorway plant genome assemblies from herbarium material from northern high-latitude regions. Our analysis reveals microbial-like sequences in many eukaryotic reference genomes, which are most pronounced in the PhyloNorway dataset. We provide a detailed map of the microbial-like regions, including genomic coordinates and taxonomic annotations. This resource enables the masking of microbial-like regions during profiling analyses, thereby improving the reliability of ancient environmental metagenomic datasets for downstream analyses.

genomics↗

bioRxiv2025

Multiplex-edited mice recapitulate woolly mammoth hair phenotypes

The woolly mammoth (Mammuthus primigenius) possessed a thick woolly coat and other cold-adaptive traits that enabled survival in harsh arctic environments. Current de-extinction efforts focus on genetically modifying the closely related Asian elephant to express woolly mammoth traits. In this study, we establish a multiplex-edited mouse model with modifications in genes associated with hair morphology and lipid metabolism, enabling insights into traits involved in developing woolly hair textures. Our optimized workflows achieved high editing efficiencies and produced genetically modified mice with simultaneous editing of up to seven different genes. Selected modifications include loss-of-function mutations in Fgf5, Tgm3, and Fam83g, among others. The resulting mice display exaggerated hair phenotypes including curly, textured coats, and golden-brown hair. This study advances methods of rapid establishment of complex genetic models. These approaches inform de-extinction efforts and research involving the genetic basis of mammalian hair development.

genetics↗

bioRxiv2022

Ghost admixture in eastern gorillas

Archaic admixture has had a significant impact on human evolution with multiple events across different clades, including from extinct hominins such as Neanderthals and Denisovans into modern humans. Within the great apes archaic admixture has been identified in chimpanzees and bonobos, but the possibility of such events has not been explored in other species. Here, we address this question using high-coverage whole genome sequences from all four extant gorilla subspecies, including six newly sequenced eastern gorillas from previously unsampled geographic regions. Using Approximate Bayesian Computation (ABC) with neural networks to model the demographic history of gorillas, we find a signature of admixture from an archaic ghost lineage into the common ancestor of eastern gorillas, but not western gorillas. We infer that up to 3% of the genome of these individuals is introgressed from an archaic lineage that diverged more than 3 million years ago from the common ancestor of all extant gorillas. This introgression event took place before the split of mountain and eastern lowland gorillas, likely more than 40 thousand years ago, and may have influenced perception of bitter taste in eastern gorillas. When comparing the introgression landscapes of gorillas, humans and bonobos, we find a consistent depletion of introgressed fragments on the X chromosome across these species. However, depletion in protein-coding content is not detectable in eastern gorillas, possibly as a consequence of stronger genetic drift in this species.

evolutionary biology↗

bioRxiv2022

aMeta: an accurate and memory-efficient ancient Metagenomic profiling workflow

Analysis of microbial data from archaeological samples is a rapidly growing field with a great potential for understanding ancient environments, lifestyles and disease spread in the past. However, high error rates have been a long-standing challenge in ancient metagenomics analysis. This is also complicated by a limited choice of ancient microbiome specific computational frameworks that meet the growing computational demands of the field. Here, we propose aMeta, an accurate ancient Metagenomic profiling workflow designed primarily to minimize the amount of false discoveries and computer memory requirements. Using simulated ancient metagenomic samples, we benchmark aMeta against a current state-of-the-art workflow, and demonstrate its superior sensitivity and specificity in both microbial detection and authentication, as well as substantially lower usage of computer memory. aMeta is implemented as a Snakemake workflow to facilitate use and reproducibility.

bioinformatics↗

bioRxiv2022

GenErode: a bioinformatics pipeline to investigate genome erosion in endangered and extinct species

BackgroundMany wild species have suffered drastic population size declines over the past centuries, which have led to genomic erosion processes characterized by reduced genetic diversity, increased inbreeding, and accumulation of harmful mutations. Yet, genomic erosion estimates of modern-day populations often lack concordance with dwindling population sizes and conservation status of threatened species. One way to directly quantify the genomic consequences of population declines is to compare genome-wide data from pre-decline museum samples and modern samples. However, doing so requires computational data processing and analysis tools specifically adapted to comparative analyses of degraded, ancient or historical, DNA data with modern DNA data as well as personnel trained to perform such analyses. ResultsHere, we present a highly flexible, scalable, and modular pipeline to compare patterns of genomic erosion using samples from disparate time periods. The GenErode pipeline uses state-of-the-art bioinformatics tools to simultaneously process whole-genome re-sequencing data from ancient/historical and modern samples, and to produce comparable estimates of several genomic erosion indices. No programming knowledge is required to run the pipeline and all bioinformatic steps are well-documented, making the pipeline accessible to users with different backgrounds. GenErode is written in Snakemake and Python3 and uses Conda and Singularity containers to achieve reproducibility on high-performance compute clusters. The source code is freely available on GitHub (https://github.com/NBISweden/GenErode). ConclusionsGenErode is a user-friendly and reproducible pipeline that enables the standardization of genomic erosion indices from temporally sampled whole genome re-sequencing data.

bioinformatics↗

bioRxiv2021

Genomic evidence for inbreeding depression and purging of deleterious genetic variation in Indian tigers

Increasing habitat fragmentation leads to wild populations becoming small, isolated, and threatened by inbreeding depression. However, small populations may be able to purge recessive deleterious alleles as they become expressed in homozygotes, thus reducing inbreeding depression and increasing population viability. We used whole genomes sequencing from 57 tigers to estimate individual inbreeding and mutation loads in a small-isolated, and two large-connected populations in India. As expected, the small-isolated population had substantially higher average genomic inbreeding (FROH=0.57) than the large-connected (FROH=0.35 and FROH=0.46) populations. The small-isolated population had the lowest loss-of-function mutation load, likely due to purging of highly deleterious recessive mutations. The large populations had lower missense mutation loads than the small-isolated population, but were not identical, possibly due to different demographic histories. While the number of the loss-of-function alleles in the small-isolated population was lower, these alleles were at high frequencies and homozygosity than in the large populations. Together, our data and analyses provide evidence of (a) high mutation load; (b) purging and (c) the highest predicted inbreeding depression, despite purging, in the small-isolated population. Frequency distributions of damaging and neutral alleles uncover genomic evidence that purifying selection has removed part of the mutation load across Indian tiger populations. These results provide genomic evidence for purifying selection in both small and large populations, but also suggest that the remaining deleterious alleles may have inbreeding associated fitness costs. We suggest that genetic rescue from sources selected based on genome-wide differentiation should offset any possible impacts of inbreeding depression. Significance statementHabitat fragmentation is sequestering species into small and isolated populations with high chances of extinction. But are small and isolated populations at risk of extinction from inbreeding depression, or does inbreeding and purging of deleterious alleles reduce such threat? Using whole genomes from several wild Indian tiger populations, we provide evidence supporting purging of highly deleterious variants in a small isolated population. However, our analyses also indicate that the remaining highly deleterious alleles are at high frequencies, suggesting continued inbreeding depression despite some successful purging. We discuss the implications of our results for conservation, including possible genomics-informed genetic rescue strategies.

evolutionary biology↗

bioRxiv2020

Competitive mapping allows to identify and exclude human DNA contamination in ancient faunal genomic datasets

BackgroundAfter over a decade of developments in field collection, laboratory methods and advances in high-throughput sequencing, contamination remains a key issue in ancient DNA research. Currently, human and microbial contaminant DNA still impose challenges on cost-effective sequencing and accurate interpretation of ancient DNA data. ResultsHere we investigate whether human contaminating DNA can be found in ancient faunal sequencing datasets. We identify variable levels of human contamination, which persists even after the sequence reads have been mapped to the faunal reference genomes. This contamination has the potential to affect a range of downstream analyses. ConclusionsWe propose a fast and simple method, based on competitive mapping, which allows identifying and removing human contamination from ancient faunal DNA datasets with limited losses of true ancient data. This method could represent an important tool for the ancient DNA field.

genomics↗

bioRxiv2019

Estimates of genetic load in small populations suggest extensive purging of deleterious alleles

It is commonly thought that declining populations will experience negative genetic consequences as a result of increased inbreeding. Here we estimated the average deleteriousness of derived alleles in a range of mammals and found that species with historically small population size and low genetic diversity often have lower genetic load than species with large population sizes. This is likely the result of genetic purging - the more efficient removal of partially deleterious recessive alleles from inbred populations. Our findings suggest that genetic purging occurs over long evolutionary time frames, and therefore rapid population declines are likely to dis-proportionally increase mutational load in species with high diversity, as they carry many deleterious alleles that can reach fixation before genetic purging can remove them.

genomics↗

bioRxiv2019

The genome of the endangered dryas monkey provides new insights into the evolutionary history of the vervets

Genomic data can be a powerful tool for inferring ecology, behaviour and conservation needs of highly elusive species, particularly when other sources of information are hard to come by. Here we focus on the Dryas monkey (Cercopithecus dryas), an endangered primate endemic to the Congo Basin with cryptic behaviour and possibly less than 250 remaining individuals. Using whole genome sequencing data we show that the Dryas monkey represents a sister lineage to the vervets (Chlorocebus sp.) and has diverged from them around 1.4 million years ago with additional bi-directional gene flow [~]750,000 - [~]500,000 years ago that has likely involved the crossing of the Congo River. Together with evidence of gene flow across the Congo River in bonobos and okapis, our results suggest that the fluvial topology of the Congo River might have been more dynamic than previously recognised. Despite the presence of several homozygous loss-of-function mutations in genes associated with sperm mobility and immunity, we find high genetic diversity and low levels of inbreeding and genetic load in the studied Dryas monkey individual. This suggests that the current population carries sufficient genetic variability for long-term survival and might be larger than currently recognised. We thus provide an example of how genomic data can directly improve our understanding of highly elusive species.

genomics↗

bioRxiv2019

Divergent mitochondrial and nuclear OXPHOS genes are candidates for genetic incompatibilities in Ficedula Flycatchers

Hybrid dysfunction is an important source of reproductive isolation between emerging species. Bateson-Dobzhansky-Muller incompatibilities are theoretically well-recognized as the underlying cause of low hybrid dysfunction. However, especially in wild populations, little empirical evidence exists for which genes are involved in such incompatibilities. The relative role of ecological divergence in causing the build-up of genetic incompatibilities in relation to other processes such as genomic conflict therefore remains largely unknown. Genes involved in energy metabolism are potential candidates for genetic incompatibilities, since energy metabolism depends on co-expression of mitochondrial DNA (mtDNA) and nuclear DNA (nDNA) leading to mitonuclear coadaptation. When mitochondrial and nuclear genes lacking a co-evolutionary history appear together in hybrids, incompatibilities could arise. Ficedula flycatcher F1 hybrids have a higher resting metabolic rate (RMR) compared to the parental species, which could be a sign of genetic incompatibilities between energy metabolism genes that diverged in response to environmental differences while the species were in allopatry. Based on sequences of 15 mitochondrial genes of 264 individuals, we show that the two species have divergent mtDNA caused by the build-up of mainly synonymous mutations and a few non-synonymous mutations. Pied flycatcher mitogenomes show evidence of non-neutrality, indicating a selective sweep or population expansion. There is little variation in the nuclear OXPHOS-related proteins and no significant deviation from neutrality, however, specific codon identified sites might be under positive selection in both mitochondrial and nuclear genes encoding OXPHOS proteins for complex I and III. Taken together, these diverged mitonuclear genes therefore constitute possible candidates underlying, at least part of the genetic incompatibilities that cause hybrid dysfunction in crosses between collared and pied flycatchers.

evolutionary biology↗

bioRxiv2018

Characterising the microbiome from host shotgun sequencing data: bacterial and diatom community dynamics derived from killer whale skin

Recent exploration into the interactions and relationship between hosts and their microbiota has revealed a connection between many aspects of the hosts biology, health and associated microorganisms. Whereas amplicon sequencing has traditionally been used to characterise the microbiome, the increasing number of published population genomics datasets offer an underexploited opportunity to study microbial profiles from the host shotgun sequencing data. Here, we use sequence data originally generated from killer whale Orcinus orca skin biopsies for population genomics, to characterise the skin microbiome and investigate how host social and geographic factors influence the microbial community composition. Having identified 845 microbial taxa from 2.4 million reads that did not map to the killer whale reference genome, we found that both ecotypic and geographic factors influence community composition of killer whale skin microbiomes. Furthermore, we uncovered key taxa that drive the microbiome community composition and showed that they are embedded in unique networks, one of which is tentatively linked to diatom presence and poor skin condition. Community composition differed between Antarctic killer whales with and without diatom coverage, suggesting that the previously reported episodic migrations of Antarctic killer whales to warmer waters associated with skin turnover may control the effects of potentially pathogenic bacteria such as Tenacibaculum dicentrarchi. Our work demonstrates the feasibility of microbiome studies from host shotgun sequencing data and highlights the importance of metagenomics in understanding the relationship between host and microbial ecology.

evolutionary biology↗

bioRxiv2017

Low rate of index hopping on the Illumina HiSeq X platform

The high-throughput capacities of the Illumina sequencing platforms and possibility to label samples individually have encouraged a wide use of sample multiplexing. However, this practice results in read misassignment (usually <1%) across samples sequenced on the same lane. Alarmingly high rates of read misassignment of up to 10% were reported for the latest generation of lllumina sequencing machines. This potentially calls into question previously generated results and may make future use of the newest generation of platforms prohibitive. In this study we rely on barcodes, short sequences that are directly ligated to both ends of the DNA insert, which allows us to quantify the amount of index hopping. Correcting for multiple sources of noise, we identify on average only 0.470% of reads containing a hopped index. Multiplexing of samples on this platform is therefore unlikely to cause markedly different results to those obtained from older platforms.

bioinformatics↗