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Biology subjects

Somel, M.

Publications and source records attributed to Somel, M..

At least 19 recordsLinked to original sources

Seven Millennia of Human Exploitation drove genomic Changes in Iberian Sheep

As one of the first domestic livestock species, sheep have played a fundamental role in human societies since the Neolithic. However, their demographic history remains poorly understood. To shed light on the demographic dynamics of sheep at the western edge of the Mediterranean, we sequenced 22 ancient sheep genomes from Iberia (dating from 7, 270 to 1, 615 calBP, sequenced up to 8.74 x coverage) along with one modern European mouflon from Corsica. We provide evidence for an initial maritime introduction into Iberia, and show that European mouflons are descendants of feralized Neolithic sheep. Further-more, we identify a secondary influx of "Eastern" genetic ancestry coinciding with the arrival of human Steppe ancestry in Iberia - an event that likely aligns with the spread of woolly sheep across Europe. A third population expansion is observed during the Roman period, a time when historical sources reference the trade of fine-wool sheep. This Roman-era expansion appears to have significantly influenced the genetic makeup of modern European sheep, contributing to the development of popular modern-day breeds such as Merino. In addition to these major events, we see indications of additional, minor episodes of prehistoric gene flow into the Iberian population, suggesting that western European sheep experienced more dynamic demographic changes than other domestic animals, humans, or sheep populations elsewhere. Together, these results highlight the dynamic history of Iberian sheep populations and demonstrate how human cultural and demographic shifts have left their hoofprints in the sheep gene pool, marking them as a valuable proxy for understanding the human past.

evolutionary biology↗

The mini yet mighty stapes: a comparison of ancient DNA yields among ossicles and the petrous bone

The petrous bone is considered the most efficient source of endogenous DNA across skeletal tissues in ancient DNA research as well as in forensic work. Recently, ancient DNA (aDNA) in auditory ossicle bones was shown to be comparably well-preserved as in the petrous, although no attempt was made to distinguish among the three ossicle bones. In this study, we used a total of 114 human ossicle- and petrous-derived sequencing libraries from similar contexts (c.10,000 BP - 7,000 BP Anatolia), including 34 matched libraries prepared from the same individuals ossicle and petrous bones. Our results suggest that endogenous human aDNA preservation in the stapes is on average two times higher than in the petrous bone; it also tends to be higher than in the malleus and incus. Similarly, aDNA fragment lengths were higher in the stapes than in the petrous, whereas postmortem damage, clonality and contamination rates were comparable. Despite being the smallest bone in the human skeleton, the stapes may be the most optimal aDNA source yet identified.

genetics↗

An age-specific burial practice reflected in ancient DNA preservation in Neolithic Catalhöyük

Selective funerary practices can inform about social relationships in prehistoric societies but are often difficult to discern. Here we present evidence for an age-specific practice at the Neolithic site of Catalhoyuk in Anatolia, dating to the 7th millennium BCE. Among ancient DNA libraries produced from 362 petrous bone samples, those of subadults contained three times higher average human DNA than those of adults. This difference in organic preservation was also confirmed by FTIR analysis. Studying similar datasets from seven prehistoric and historical sites, we found a similar age-related difference in only one cemetery. We propose that the organic preservation difference with age was caused by the special treatment of chosen corpses before interment, such as defleshing or drying, which was more frequently applied to Catalhoyuk adults and promoted organic decay.

evolutionary biology↗

Ancient DNA analyses of two Early Chalcolithic Individuals from the West Mound

In this chapter, we investigate the genetics of two Early Chalcolithic Catalhoyuk individuals, U.18333 and U.16835, the only two burials yet recovered from the West Mound. These were two neonates buried within the same building. Using shotgun-sequenced partial genomes (0.06x and 0.02x coverage) we identify both as females. Despite being recovered from the same building, we find no close genetic kinship between them, in line with previously published kinship results from Catalhoyuk. We also find that the two West Mound neonates shared the same gene pool with Neolithic Catalhoyuk and other Central and West Anatolian Neolithic populations, and they did not carry the Caucasus-related "eastern" gene flow signature observed in later-coming Chalcolithic Anatolian genomes. This indicates no large-scale admixture between East and West Mound Catalhoyuk, and possibly that the post-Neolithic "eastern" gene flow event into Anatolia may have initiated only by the mid-6th millennium BCE.

genetics↗

DeepKin: Predicting relatedness from low-coverage genomes and paleogenomes with convolutional neural networks

DeepKin is a novel tool designed to predict relatedness from genomic data using convolutional neural networks (CNNs). Traditional methods for estimating relatedness often struggle when genomic data is limited, as with paleogenomes and degraded forensic samples. DeepKin addresses this challenge by leveraging two CNN models trained on simulated genomic data to classify relatedness up to the third-degree and to identify parent-offspring and sibling pairs. Our benchmarking shows DeepKin performs comparably or better than the widely used tool READv2. We validated DeepKin on empirical paleogenomes from two paleological sites, demonstrating its robustness and adaptability across different genetic backgrounds, with accuracy >90% above 10K shared SNPs. By capturing information across genomic segments, DeepKin offers a new methodological path for relatedness estimation in settings with highly degraded samples, with applications in ancient DNA, as well as forensic and conservation genetics.

bioinformatics↗

Out-of-Anatolia: cultural and genetic interactions during the Neolithic expansion in the Aegean

Western Anatolia has been a crucial yet elusive element in the Neolithic expansion from the Fertile Crescent to Europe. Using 30 new palaeogenomes from Anatolia c.8000-6000 BCE we describe the early Holocene genetic landscape of Western Anatolia, which reveals population continuity since the late Upper Pleistocene. Our findings indicate that the Neolithisation of Western Anatolia in the 7th millennium BCE was a multifaceted process, characterised by the assimilation of Neolithic practices by indigenous groups and the influx of populations from the east, their admixed descendants eventually laying the foundations of Neolithic Southeast Europe. Intriguingly, the observed diversity in material culture among Aegean Early Neolithic communities correlates with their geographical distances but not their genetic differences, signifying a decoupling between cultural developments and genetic admixture processes.

genomics↗

An explanation for the neighbour repulsion phenomenon in Patterson's f-statistics

Pattersons f-statistics are among the most heavily utilized tools for analysing genome-wide allele frequency data for demographic inference. Beyond studying admixture, f3 and f4 statistics are also used for clustering populations to identify groups with similar histories. However, previous studies have noted an unexpected behaviour of f-statistics: multiple populations from a certain region systematically show higher genetic affinity to a more distant population than to their neighbours, a pattern that is mismatched with alternative measures of genetic similarity. We call this counter-intuitive pattern "sister repulsion". We first present a novel instance of sister repulsion, where genomes from Bronze Age East Anatolian sites show higher affinity towards Bronze Age Greece rather than each other. This is observed both using f3- and f4-statistics, contrasts with archaeological/historical expectation, and also contradicts genetic affinity patterns captured using PCA or MDS on genetic distances. We then propose a simple demographic model to explain this pattern, where sister populations receive gene flow from a genetically distant source. We calculate f3- and f4-statistics using simulated genetic data with varying population genetic parameters, confirming that low-level gene flow from an external source into populations from one region can create sister repulsion in f-statistics. Unidirectional gene flow between the studied regions (without an external source) can likewise create repulsion. Meanwhile, similar to our empirical observations, MDS analyses of genetic distances still cluster sister populations together. Overall, our results highlight the impact of low-level admixture events when inferring demographic history using f-statistics.

genetics↗

READv2: Advanced and user-friendly detection of biological relatedness in archaeogenomics

The possibility to obtain genome-wide ancient DNA data from multiple individuals has facilitated an unprecedented perspective into prehistoric societies. Studying biological relatedness in these groups requires tailored approaches for analyzing ancient DNA due to its low coverage, post-mortem damage, and potential ascertainment bias. Here we present READv2 (Relatedness Estimation from Ancient DNA version 2), an improved Python 3 re-implementation of the most widely used tool for this purpose. While providing increased portability and making the software future-proof, we are also able to show that READv2 (a) is orders of magnitude faster than its predecessor; (b) has increased power to detect pairs of relatives using optimized default parameters; and, when the number of overlapping SNPs is sufficient, (c) can differentiate between full-siblings and parent-offspring, and (d) can classify pairs of third-degree relatedness. We further use READv2 to analyze a large empirical dataset that has previously needed two separate tools to reconstruct complex pedigrees. We show that READv2 yields results and precision similar to the combined approach but is faster and simpler to run. READv2 will become a valuable part of the archaeogenomic toolkit in providing an efficient and user-friendly classification of biological relatedness from pseudohaploid ancient DNA data.

bioinformatics↗

Population genomic history of the endangered Anatolian and Cyprian mouflons in relation to worldwide wild, feral and domestic sheep lineages

Once widespread in their homelands, Anatolian mouflon (Ovis gmelini anatolica) and Cyprian mouflon (Ovis gmelini ophion) were driven to near extinction during the 20th century and are currently listed as endangered populations by the IUCN. While the exact origins of these lineages remain unclear, they have been suggested to be close relatives of domestic sheep or remnants of proto-domestic sheep groups. Here, we study whole genome sequences of n=5 Anatolian mouflons and n=10 Cyprian mouflons in terms of population history and diversity, relative to eight other extant sheep lineages. We find reciprocal genetic affinity between Anatolian and Cyprian mouflons and domestic sheep, higher than all other studied wild sheep genomes, including the Iranian mouflon (Ovis gmelini). Despite similar recent population dynamics, Anatolian and Cyprian mouflons exhibit disparate diversity levels, which can potentially be attributed to founder effects, island isolation, introgression from domestic lineages, or different bottleneck dynamics. The lower relative mutation load found in Cyprian compared to Anatolian mouflons suggests the purging of recessive deleterious variants in the former. This agrees with estimates of a long-term small effective population size in the Cyprian mouflon. Both subspecies harbor considerable numbers of runs of homozygosity (ROH) blocks <2 Mb, which reflects the effect of small population size. Expanding our analyses to worldwide wild and feral Ovis genomes, we observe varying viability metrics among different lineages, and a limited consistency between viability metrics and conservation status. Factors such as recent inbreeding, introgression, and unique population dynamics may contribute to the observed disparities.

evolutionary biology↗

Pre-processing of paleogenomes: Mitigating reference bias and postmortem damage in ancient genome data

Ancient DNA analysis is subject to various technical challenges, including bias towards the reference allele ("reference bias"), postmortem damage (PMD) that confounds real variants, and limited coverage. Here, we conduct a systematic comparison of alternative approaches against reference bias and against PMD. To reduce reference bias, we either (a) mask variable sites before alignment or (b) align the data to a graph genome representing all variable sites. Compared to alignment to the linear reference genome, both masking and graph alignment effectively remove allelic bias when using simulated or real ancient human genome data, but only if sequencing data is available in FASTQ or unfiltered BAM format. Reference bias remains indelible in quality-filtered BAM files and in 1240K-capture data. We next study three approaches to overcome postmortem damage: (a) trimming, (b) rescaling base qualities, and (c) a new algorithm we present here, bamRefine, which masks only PMD-vulnerable polymorphic sites. We find that bamRefine is optimal in increasing the number of genotyped loci up to 20% compared to trimming and in improving accuracy compared to rescaling. We propose graph alignment coupled with bamRefine to minimise data loss and bias. We also urge the paleogenomics community to publish FASTQ files.

bioinformatics↗

Benchmarking kinship estimation tools for ancient genomes using pedigree simulations

There is growing interest in uncovering genetic kinship patterns in past societies using low-coverage paleogenomes. Here, we benchmark four tools for kinship estimation with such data: lcMLkin, NgsRelate, KIN, and READ, which differ in their input, IBD-estimation methods and statistical approaches. We used pedigree and ancient genome sequence simulations to evaluate these tools when only a limited number (1K to 50K) of shared SNPs (with minor allele frequency [&ge;]0.01) are available. The performance of all four tools was comparable using [&ge;]20K SNPs. We found that first-degree related pairs can be accurately classified even with 1K SNPs, with 85% F1 scores using READ and 96% using NgsRelate or lcMLkin. Distinguishing third-degree relatives from unrelated pairs or second-degree relatives was also possible with high accuracy (F1 >90%) with 5K SNPs using NgsRelate and lcMLkin, while READ and KIN showed lower success (69% and 79%, respectively). Meanwhile, noise in population allele frequencies and inbreeding (first cousin mating) led to deviations in kinship coefficients, with different sensitivities across tools. We conclude that using multiple tools in parallel might be an effective approach to achieve robust estimates on ultra-low coverage genomes.

genetics↗

Investigating DNA methylation changes associated with food production using paleogenomes

AO_SCPLOWBSTRACTC_SCPLOWThe Neolithic transition introduced major diet and lifestyle changes to human populations across continents. Beyond well-documented bioarchaeological and genetic effects, whether these changes also had molecular-level epigenetic repercussions in past human populations has been an open question. In fact, methylation signatures can be inferred from UDG-treated ancient DNA through postmortem damage patterns, but with low signal-to-noise ratios; it is thus unclear whether published paleogenomes would provide the necessary resolution to discover systematic effects of lifestyle and diet shifts. To address this we compiled UDG-treated shotgun genomes of 13 pre-Neolithic hunter-gatherer (HGs) and 21 Neolithic farmer (NFs) individuals from West and North Eurasia, published by six different laboratories and with coverage c.1x-58x (median=9x). We used epiPALEOMIX and a Monte Carlo normalization scheme to estimate methylation levels per genome. Our paleomethylome dataset showed expected genome-wide methylation patterns such as CpG island hypomethylation. However, analysing the data using various approaches did not yield any systematic signals for subsistence type, genetic sex, or tissue effects. Comparing the HG-NF methylation differences in our dataset with methylation differences between hunter-gatherers vs. farmers in modern-day Central Africa also did not yield consistent results. Meanwhile, paleomethylome profiles did cluster strongly by their laboratories of origin. Our results mark the importance of minimizing technical noise for capturing subtle biological signals from paleomethylomes.

evolutionary biology↗

Ancient Sheep Genomes reveal four Millennia of North European Short-Tailed Sheep in the Baltic Sea region

Sheep are among the earliest domesticated livestock species, with a wide variety of breeds present today. However, it remains unclear how far back this breed diversity goes, with formal documentation only dating back a few centuries. North European short-tailed breeds are often assumed to be among the oldest domestic sheep populations, even thought to represent relicts of the earliest sheep expansions during the Neolithic period reaching Scandinavia less than 6000 years ago. This study sequenced the genomes (up to 11.6X) of five sheep remains from the Baltic islands of Gotland and [A]land, dating from Late Neolithic ([~]4100 calBP) to historical times ([~]1600 CE). Our findings indicate that these ancient sheep largely possessed the genetic characteristics of modern North European short-tailed breeds, suggesting a substantial degree of long-term continuity of this breed type in the Baltic Sea region. Despite the wide temporal spread, population genetic analyses show high levels of affinity between the ancient genomes and they also exhibit higher genetic diversity when compared to modern breeds, implying a loss of diversity in recent centuries associated with breed formation. Finally, we see a potential signature of an even earlier, genetically different form of sheep in Scandinavia as these samples do not represent the first sheep in Northern Europe. Our results shed light on the development of breeds in Northern Europe specifically as well as the development of genetic diversity in sheep breeds, and their expansion from the domestication center in general.

evolutionary biology↗

The first complete genome of the extinct European wild ass (Equus hemionus hydruntinus)

We present paleogenomes of three morphologically-unidentified Anatolian equids dating to the 1st millennium BCE, sequenced to coverages of 0.6-6.4X. Mitochondrial DNA haplotypes of the Anatolian individuals clustered with those of Equus hydruntinus (or Equus hemionus hydruntinus), the extinct European wild ass. The Anatolian wild ass whole genome profiles fall outside the genomic diversity of other extant and past Asiatic wild ass (E.hemionus) lineages. These observations strongly suggest that the three Anatolian wild asses represent E.hydruntinus, making them the latest recorded survivors of this lineage, about a millennium later than the latest observations in the zooarchaeological record. Comparative genomic analyses suggest that E.hydruntinus was a sister clade to all ancient and present-day E.hemionus lineages, representing an early split. We also find indication of gene flow between hydruntines and Middle Eastern wild asses. Analyses of genome-wide heterozygosity and runs of homozygosity reveal that the Anatolian wild ass population had severely lost genetic diversity by the mid-1st millennium BCE, a likely omen of its eventual demise.

genomics↗

Under the shadow: Old-biased genes are subject to weak purifying selection at both the tissue and cell type-specific levels

The mutation accumulation theory predicts that aging is caused by accumulation of late-acting deleterious variants in the germ-line, due to weak purifying selection at old age. In accordance with this model, we and others have shown that sequence conservation among old-biased genes (with higher expression in old versus young adults) is weaker than among young-biased genes across a number of mammalian and insect species. However, questions remained regarding the source and generality of this observation. It was especially unclear whether the observed patterns were driven by tissue and cell type composition shifts or by cell-autonomous expression changes during aging. How wide this trend would extend to non-mammalian metazoan aging was also uncertain. Here we analyzed bulk tissue as well as cell type-specific RNA sequencing data from diverse animal taxa across six different datasets from five species. We show that the previously reported age-related decrease in transcriptome conservation (ADICT) is commonly found in aging tissues of non-mammalian species, including non-mammalian vertebrates (chicken brain, killifish liver and skin) and invertebrates (fruit fly brain). Analyzing cell type-specific transcriptomes of adult mice, we further detect the same ADICT trend at the single cell type level. Old-biased genes are less conserved across the majority of cell types analyzed in the lung, brain, liver, muscle, kidney, and skin, and these include both tissue-specific cell types, and also ubiquitous immune cell types. Overall, our results support the notion that aging in metazoan tissues may be at least partly shaped by the mutation accumulation process.

evolutionary biology↗

MTaxi : A comparative tool for taxon identification of ultra low coverage ancient genomes

A major challenge in zooarchaeology is to morphologically distinguish closely related species remains, especially using small bone fragments. Shotgun sequencing aDNA from archeological remains and comparative alignment to the candidate species reference genomes will only apply when reference nuclear genomes of comparable quality are available, and may still fail when coverages are low. Here, we propose an alternative method, MTaxi, that uses highly accessible mitochondrial DNA (mtDNA) to distinguish between pairs of closely related species from ancient DNA sequences. MTaxi utilises mtDNA transversion-type substitutions between pairs of candidate species, assigns reads to either species, and performs a binomial test to determine the sample taxon. We tested MTaxi on sheep/goat and horse/donkey data, between which zooarchaeological classification can be challenging in ways that epitomise our case. The method performed efficiently on simulated ancient genomes down to 0.5x mitochondrial coverage for both sheep/goat and horse/donkey, with no false positives. Trials on n=18 ancient sheep/goat samples and n=10 horse/donkey samples of known species identity with mtDNA coverages 0.1x - 12x also yielded 100% accuracy. Overall, MTaxi provides a straightforward approach to classify closely related species that are compelling to distinguish through zooarchaeological methods using low coverage aDNA data, especially when similar quality reference genomes are unavailable. MTaxi is freely available at https://github.com/goztag/MTaxi.

bioinformatics↗

Somatic copy number variant load in neurons of healthy controls and Alzheimer's disease patients

BackgroundThe possible role of somatic copy number variations (CNVs) in Alzheimers disease (AD) aetiology has been controversial. Although cytogenetic studies suggested increased CNV loads in AD brains, a recent single-cell whole-genome sequencing (scWGS) experiment, studying frontal cortex brain samples, found no such evidence. Here we readdressed this issue using lowcoverage scWGS on pyramidal neurons dissected using laser capture microdissection (LCM) across five brain regions: entorhinal cortex, temporal cortex, hippocampal CA1, hippocampal CA3, and the cerebellum. ResultsAmong reliably detected somatic CNVs identified in 1301 cells obtained from the brains of 13 AD patients and 7 healthy controls, deletions were more frequent compared to duplications. Interestingly, we observed slightly higher frequencies of CNV events in cells from AD compared to similar numbers of cells from controls (4.1% vs. 1.4%, or 0.9% vs. 0.7%, using different filtering approaches), although the differences were not statistically significant. We also observed that LCM-isolated cells show higher within-cell read depth variation compared to cells isolated with fluorescence activated cell sorting (FACS), which we argue may have both biological and technical causes. Furthermore, we found that LCM-isolated neurons in AD harbour slightly more read depth variability than neurons of controls, which might be related to the reported hyperploid profiles of some AD-affected neurons. We also propose a principal component analysis-based denoising approach that significantly reduces within-cell read depth variation in scWGS data. ConclusionsWe find slightly higher somatic CNV frequencies in the brains of AD patients, and higher sequencing coverage variability, although the effects measured do not reach statistical significance. The results call for improved experimental protocols to determine the possible role of CNVs in AD pathogenesis.

bioinformatics↗

A genomic snapshot of demographic and cultural dynamism in Upper Mesopotamia during the Neolithic Transition

Upper Mesopotamia played a key role in the Neolithic Transition in Southwest Asia through marked innovations in symbolism, technology, and foodways. We present thirteen ancient genomes (c.8500-7500 calBCE) from Pre-Pottery Neolithic Cayonu in the Tigris basin together with bioarchaeological and material culture data. Our findings reveal that Cayonu was a genetically diverse population, carrying a mixed ancestry from western and eastern Fertile Crescent, and that the community received immigrants. Our results further suggest that the community was organised along biological family lines. We document bodily interventions such as head-shaping and cauterization among the individuals examined, reflecting Cayonus cultural ingenuity. Finally, we identify Upper Mesopotamia as the likely source of eastern gene flow into Neolithic Anatolia, in line with material culture evidence. We hypothesise that Upper Mesopotamias cultural dynamism during the Neolithic Transition was the product not only of its fertile lands but also of its interregional demographic connections.

genetics↗