Biology subjects

Slon, V.

Publications and source records attributed to Slon, V..

7 recordsLinked to original sources

bioRxiv2026

Widespread 3-Base Periodicity in Complex DNA Mixtures and an Alignment-Free Algorithm to Uncover its Source

Background: Protein-coding DNA exhibits characteristic three-base periodicity. In unaligned DNA libraries, however, this signal should cancel if fragment boundaries are uniformly distributed across codon phases. Yet, we find that in multiple metagenomic libraries, base frequencies depended systematically on distance from fragment boundaries, producing a period-3 pattern. We investigated the origin of this unexpected signal. Results: The signal was observed in modern metagenomic datasets and widely across ancient-DNA datasets. We developed a new alignment-free algorithm to infer latent triplet-phase structure from nucleotide composition. The inferred shifts were strongly nonuniform at fragment boundaries, explaining the read-coordinate periodicity. We initially suspected a protocol artifact. To test an alternative, we derived a probabilistic framework linking nucleotide-dependent boundary selection to codon-phase frequencies. The framework showed that, because nucleotide composition differs among codon positions, preferential breakage at particular nucleotides biases the phases represented at fragment boundaries. Simulations confirmed this mechanism: purine-associated fragmentation produced strong period-3 coherence in a coding-dense bacterial genome, whereas no comparable genome-wide effect appeared in the human reference genome. Conclusions: The observed read-coordinate three-base periodicity does not require an intrinsic phase bias in the source DNA. Instead, sequence-dependent fragment formation or recovery can couple boundaries to codon phase. Purine-associated post-mortem fragmentation plausibly explains the widespread phenomenon in ancient-DNA libraries, although PCR- or library-specific mechanisms may contribute to it in modern datasets. Our alignment-free algorithm provides a practical method for estimating and normalizing phase shifts before searching for positional nucleotide patterns, preventing boundary-associated bias from being mistaken for an intrinsic biological pattern.

bioinformatics↗

bioRxiv2026

A Method to Analyze Low-Quality Archaic Human Genomes and its Application to the Teshik-Tash 1 Neandertal

The Teshik-Tash 1 child whose remains were found in Uzbekistan represents the southeastern-most extent of the known Neandertal range, providing an important link with the better studied Caucasus and Altai Mountain ranges. However, due to poor DNA preservation, studying the genetics of Teshik Tash 1 has remained elusive. Here we present analyses of the nuclear DNA from the Teshik-Tash 1, from extracts that are highly contaminated with present-day human DNA. To achieve this, we developed a new computational method, admixslug, that jointly models contamination and population relationships, in order to infer the relationship of a target individual from which only low-quality nuclear DNA is available, to high-quality archaic human genomes. After validating admixslug, we show that Teshik-Tash 1 is genetically more similar to later Neandertals from Western Eurasia than to older Neandertals from the Altai Mountains. We estimate that Teshik-Tash 1 split from the Western Eurasian lineage between 80,000 and 100,000 years ago. Despite the geographical proximity of Teshik-Tash 1 to the Denisovan range, we find no evidence for Denisovan ancestry in his genome. Our results demonstrate that admixslug enables the study of archaic human specimens in cases where DNA preservation was previously considered too poor for population genetic analyses.

genetics↗

bioRxiv2026

Evaluating the applicability of kinship analyses for sedimentary ancient DNA datasets

Kinship reconstruction in ancient populations provides key insights into past social organization and evolutionary history. Sedimentary ancient DNA (sedaDNA) enables access to deep-time human populations in the absence of skeletal remains. However, it is characterized by severe degradation and the potential mixture of genetic material from multiple individuals, raising questions about its suitability for kinship inference. Here, we use extensive simulations to evaluate the feasibility and limitations of kinship inference in sparse and damaged sedaDNA data, with a focus on Neandertals. We find that the main obstacle to accurate kinship inference in sedaDNA is the presence of multiple contributors to a given sample. To address this, we introduce a simple heterozygosity-based test to identify samples containing DNA from multiple individuals. Guided by these results, we analyze published Neandertal sedaDNA from the Galeria de las Estatuas site to assess the practical limits of kinship inference in real sedimentary ancient DNA data. Together, our results define methodological considerations and practical limits for kinship inference in sedimentary ancient DNA.

bioinformatics↗

bioRxiv2025

Evaluating rapid extraction methods for recovering ancient DNA from archaeological sediments

Sedimentary ancient DNA (aDNA) provides a powerful means to reconstruct past environments and populations. However, sedimentary aDNA research is hindered by low success rates due to poor DNA preservation, the largely opportunistic nature of field sampling, and long delays between sampling and results--meaning that substantial time and effort are often spent on samples that eventually yield little or no aDNA. On-site screening methods could thus be particularly valuable when site access is temporary (e.g., seasonal excavations, salvage operations, or in regions affected by geopolitical instability), where delays or poor preservation can mean missed opportunities to recover optimal samples. Here, we compared three rapid DNA extraction protocols--an Amicon ultrafiltration method, an alkaline lysis approach, and a cellulose paper-binding method--across three sediment types (clay, sand, and soil), benchmarking them against a silica-based protocol optimized for ancient sediments but designed for laboratory rather than field conditions. We found that the Amicon-based method, originally validated on ancient bones and coprolites, and which we modified here to enhance the recovery of very short fragments, recovered from sediments both short synthetic DNA and modern DNA sheared to mimic aDNA, outperforming the other rapid methods. When applied to Pleistocene and Holocene archaeological sediments, this method successfully recovered amplifiable aDNA within approximately three hours. While not a replacement for laboratory extractions, this rapid, portable, non-hazardous approach adds a practical tool to the sedimentary aDNA research toolkit, enabling rapid on-site assessment of aDNA preservation and supporting informed sampling in time-sensitive or logistically constrained excavations.

evolutionary biology↗

bioRxiv2025

Genomic signatures of increasing disease burden in recent prehistory

One of the strongest selection pressures experienced by human populations is that driven by diseases on immune-related genomic regions. While it has been hypothesized for some time that disease burdens increased with the shift to agricultural and urbanized lifestyles, direct evidence for this hypothesis is lacking. Here, we capitalize on the accumulation of ancient genomic data to study changes in disease burden in human populations over the past 12,000 years. We investigated changes in genetic diversity and balancing selection in two distinct geographical and cultural centers in Southwest Eurasia and Eastern Asia, and found that not only is the major histocompatibility complex (MHC) the genomic region with the most substantial increases in diversity in terms of enrichment of genes and rates of increase, but that the rates of changes for individual genes are highly correlated between the two cultural centers, indicating similar selection pressures. We identify periods of time with substantial peaks in MHC diversity increase that primarily correspond to periods with settlement intensification, increased connectivity, and the expansion of animal domestication, which suggest that the most intensive disease burden occurred following the transition to sedentary lifestyle but prior to urbanization. These findings demonstrate the potential of our approach in uncovering the interplay between cultural shifts and selection, and provide strong support to the hypothesis that the levels of disease burden have substantially increased in recent prehistory following changes in lifestyle, connectivity and the introduction of domesticated animals.

evolutionary biology↗

bioRxiv2020

A high-coverage Neandertal genome from Chagyrskaya Cave

We sequenced the genome of a Neandertal from Chagyrskaya Cave in the Altai Mountains, Russia, to 27-fold genomic coverage. We estimate that this individual lived ~80,000 years ago and was more closely related to Neandertals in western Eurasia (1,2) than to Neandertals who lived earlier in Denisova Cave (3), which is located about 100 km away. About 12.9% of the Chagyrskaya genome is spanned by homozygous regions that are between 2.5 and 10 centiMorgans (cM) long. This is consistent with that Siberian Neandertals lived in relatively isolated populations of less than 60 individuals. In contrast, a Neandertal from Europe, a Denisovan from the Altai Mountains and ancient modern humans seem to have lived in populations of larger sizes. The availability of three Neandertal genomes of high quality allows a first view of genetic features that were unique to Neandertals and that are likely to have been at high frequency among them. We find that genes highly expressed in the striatum in the basal ganglia of the brain carry more amino acid-changing substitutions than genes expressed elsewhere in the brain, suggesting that the striatum may have evolved unique functions in Neandertals.

genomics↗

bioRxiv2018

The Genomic Formation of South and Central Asia

The genetic formation of Central and South Asian populations has been unclear because of an absence of ancient DNA. To address this gap, we generated genome-wide data from 362 ancient individuals, including the first from eastern Iran, Turan (Uzbekistan, Turkmenistan, and Tajikistan), Bronze Age Kazakhstan, and South Asia. Our data reveal a complex set of genetic sources that ultimately combined to form the ancestry of South Asians today. We document a southward spread of genetic ancestry from the Eurasian Steppe, correlating with the archaeologically known expansion of pastoralist sites from the Steppe to Turan in the Middle Bronze Age (2300-1500 BCE). These Steppe communities mixed genetically with peoples of the Bactria Margiana Archaeological Complex (BMAC) whom they encountered in Turan (primarily descendants of earlier agriculturalists of Iran), but there is no evidence that the main BMAC population contributed genetically to later South Asians. Instead, Steppe communities integrated farther south throughout the 2nd millennium BCE, and we show that they mixed with a more southern population that we document at multiple sites as outlier individuals exhibiting a distinctive mixture of ancestry related to Iranian agriculturalists and South Asian hunter-gathers. We call this group Indus Periphery because they were found at sites in cultural contact with the Indus Valley Civilization (IVC) and along its northern fringe, and also because they were genetically similar to post-IVC groups in the Swat Valley of Pakistan. By co-analyzing ancient DNA and genomic data from diverse present-day South Asians, we show that Indus Periphery-related people are the single most important source of ancestry in South Asia--consistent with the idea that the Indus Periphery individuals are providing us with the first direct look at the ancestry of peoples of the IVC--and we develop a model for the formation of present-day South Asians in terms of the temporally and geographically proximate sources of Indus Periphery-related, Steppe, and local South Asian hunter-gatherer-related ancestry. Our results show how ancestry from the Steppe genetically linked Europe and South Asia in the Bronze Age, and identifies the populations that almost certainly were responsible for spreading Indo-European languages across much of Eurasia.\n\nOne Sentence SummaryGenome wide ancient DNA from 357 individuals from Central and South Asia sheds new light on the spread of Indo-European languages and parallels between the genetic history of two sub-continents, Europe and South Asia.

genomics↗