Biology subjects

Gunther, T.

Publications and source records attributed to Gunther, T..

9 recordsLinked to original sources

bioRxiv2026

Rethinking human AMY1 copy number evolution in light of demographic history

Dietary change is often invoked as a major selective force in recent human evolution, with increased copy number of the salivary amylase gene (AMY1) widely cited as an adaptation to starch-rich agricultural diets. However, most evidence for this model comes from limited geographical sampling and analyses that do not fully account for shared ancestry. Here we combine newly generated droplet digital PCR estimates from 390 individuals representing 30 Sub-Saharan African populations with published copy number data from up to 1,307 individuals worldwide and re-evaluate AMY1 evolution using ancestry-aware and phylogenetically informed models. Across Africa, AMY1 copy number shows no consistent association with agriculture once population structure is accounted for. At a global scale, differences between agriculturalists and non-agriculturalists are substantially smaller than previously reported and are largely explained by shared ancestry rather than diet. Phylogenetic analyses further reveal baseline differences in AMY1 copy number between Sub-Saharan and non-Sub-Saharan populations, pointing to deep demographic processes shaping present-day variation. These results challenge the long-standing "agriculture hypothesis" and identify demographic history, rather than subsistence strategy, as the primary driver of AMY1 CN evolution worldwide.

evolutionary biology↗

bioRxiv2025

Oncogenic virus hijacks SOX18 pioneer function to enhance viral persistence

Kaposis sarcoma herpesvirus (KSHV) establishes lifelong oncogenic infection in lymphatic endothelial cells (LECs) by ensuring episomal maintenance of its genome via the viral protein LANA. Efficient viral genome maintenance typically involves host DNA replication and episome tethering, but the extent of cell-type-specific regulation remains unclear. Here, we identify that KSHV hijacks the pioneering function of the endothelial-specific transcription factor SOX18 to facilitate persistence of viral episomes. Upon infection, LANA co-opts SOX18 to recruit the SWI/SNF chromatin-remodeling complex via its ATPase subunit BRG1, enhancing chromatin accessibility and enabling efficient viral genome persistence. Disruption of SOX18 or BRG1--genetically or pharmacologically--leads to reduced episome load and attenuated hallmarks of virus infection. This work highlights how viruses can harness lineage-specific transcriptional regulators to establish persistent nuclear retention of their episome into the host genome.

molecular biology↗

bioRxiv2024

Repression of CADM1 transcription by HPV type 18 is mediated by three-dimensional rearrangement of promoter-enhancer interactions

Upon infection, human papillomavirus (HPV) manipulates host cell gene expression to create an environment that is supportive of a productive and persistent infection. The virus-induced changes to the host cells transcriptome are thought to contribute to carcinogenesis. Here, we show by RNA-sequencing that oncogenic HPV18 episome replication in primary human foreskin keratinocytes (HFKs) drives host transcriptional changes that are consistent between multiple HFK donors. We have previously shown that HPV18 episome replication in HFKs results in post-transcriptional stabilisation of the host chromatin insulation protein CTCF. Since CTCF is an important regulator of host cell transcription via coordination of epigenetic boundaries and long-range chromosomal interactions, we hypothesised that HPV18-induced stabilisation of CTCF may contribute to host transcription reprogramming. Analysis of CTCF binding in the host cell genome by ChIP-Seq revealed that while the total number of CTCF binding sites is not altered by the virus, there are a sub-set of CTCF binding sites that are either enriched or depleted of CTCF. Many of these altered sites are clustered within regulatory elements of differentially expressed genes, including the tumour suppressor gene cell adhesion molecule 1 (CADM1), which supresses epithelial cell growth and invasion. We show that HPV18 establishment results in reduced CTCF binding at the CADM1 promoter and upstream enhancer. Loss of CTCF binding is coincident with epigenetic repression of CADM1, in the absence of CpG hypermethylation, while adjacent genes including the transcriptional regulator ZBTB16 are activated. These data indicate that the CADM1 locus is subject to topological rearrangement following HPV18 establishment. We tested this hypothesis using 4C-Seq (circular chromosome confirmation capture-sequencing) and show that HPV18 establishment causes a loss of long-range chromosomal interactions between the CADM1 transcriptional start site and the upstream transcriptional enhancer. These data show that HPV18 manipulates host cell promoter-enhancer interactions to drive transcriptional reprogramming that may contribute to HPV-induced disease progression. AUTHOR SUMMARYInfection with oncogenic HPV is the cause of numerous cancer types, which generally arise after persistent HPV infection. Upon infection, HPV alters the gene expression profile of infected cells to facilitate virus replication and persistence. Multiple mechanisms of HPV-induced host cell reprogramming have been previously suggested. Here, we show that HPV infection induces rearrangement of specific genomic loci by altering the chromatin binding of the host cell protein CTCF, an important regulator of chromatin architecture. Loss of CTCF binding to a cluster of binding sites at the CADM1 locus on chromosome 11 is coincident with epigenetic reprogramming and disruption of long-range chromatin interactions, resulting in transcriptional repression of CADM1. Our data show that repression of CADM1 is an early event in HPV-driven disease, preceding hypermethylation of the CADM1 transcriptional promoter that is frequently observed in HPV-driven cancers, demonstrating a novel mechanism of HPV-induced host cell transcriptional reprogramming.

microbiology↗

bioRxiv2023

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↗

bioRxiv2021

Disentangling adaptation from drift in bottlenecked and reintroduced populations of Alpine ibex

Identifying local adaptation in bottlenecked species is essential for effective conservation management. Selection detection methods are often applied to bottlenecked species and have an important role in species management plans, assessments of the species adaptive capacity, and looking for responses to major threats like climate change. Yet, the allele frequency changes driven by selection and exploited in selection detection methods, are similar to those caused by the strong neutral genetic drift expected during a bottleneck. Consequently, it is often unclear what accuracy selection detection methods may offer within bottlenecked populations. In this study, we used simulations to explore if signals of selection could be confidently distinguished from genetic drift across 23 bottlenecked and reintroduced populations of Alpine ibex (Capra ibex). We used the meticulously recorded demographic history of the Alpine ibex to generate a comprehensive simulated SNP data. The simulated SNPs were then used to benchmark the confidence we could place in putative outliers identified through selection scans on empirical Alpine ibex SNP data. Within the simulated dataset, the false positive rates were high for all selection detection methods but fell substantially when two or more selection detection methods were combined. However, the true positive rates were consistently low and became essentially negligible after this increased stringency. Despite the detection of many putative outlier loci in the empirical Alpine ibex RADseq data, none met the threshold needed to distinguish them from genetic drift-driven false positives. Unfortunately, the low true positive rate also creates a paradox, by preventing the exclusion of recent local adaptation within the Alpine ibex.

evolutionary biology↗

bioRxiv2019

Robust Genome-Wide Ancestry Inference for Heterogeneous Datasets and Ancestry Facial Imaging based on the 1000 Genomes Project

Accurate inference of genomic ancestry is critically important in human genetics, epidemiology, and related fields. Geneticists today have access to multiple heterogeneous population-based datasets from studies collected under different protocols. Therefore, joint analyses of these datasets require robust and consistent inference of ancestry, where a common strategy is to yield an ancestry space generated by a reference dataset. However, such a strategy is sensitive to batch artefacts introduced by different protocols. In this work, we propose a novel robust genome-wide ancestry inference method; referred to as SUGIBS, based on an unnormalized genomic (UG) relationship matrix whose spectral (S) decomposition is generalized by an Identity-by-State (IBS) similarity degree matrix. SUGIBS robustly constructs an ancestry space from a single reference dataset, and provides a robust projection of new samples, from different studies. In experiments and simulations, we show that, SUGIBS is robust against individual outliers and batch artifacts introduced by different genotyping protocols. The performance of SUGIBS is equivalent to the widely used principal component analysis (PCA) on normalized genotype data in revealing the underlying structure of an admixed population and in adjusting for false positive findings in a case-control admixed GWAS. We applied SUGIBS on the 1000 Genome project, as a reference, in combination with a large heterogeneous dataset containing auxiliary 3D facial images, to predict population stratified average or ancestry faces. In addition, we projected eight ancient DNA profiles into the 1000 Genome ancestry space and reconstructed their ancestry face. Based on the visually strong and recognizable human facial phenotype, comprehensive facial illustrations of the populations embedded in the 1000 Genome project are provided. Furthermore, ancestry facial imaging has important applications in personalized and precision medicine along with forensic and archeological DNA phenotyping. Author SummaryEstimates of individual-level genomic ancestry are routinely used in human genetics, epidemiology, and related fields. The analysis of population structure and genomic ancestry can yield significant insights in terms of modern and ancient population dynamics, allowing us to address questions regarding the timing of the admixture events, and the numbers and identities of the parental source populations. Unrecognized or cryptic population structure is also an important confounder to correct for in genome-wide association studies (GWAS). However, to date, it remains challenging to work with heterogeneous datasets from multiple studies collected by different laboratories with diverse genotyping and imputation protocols. This work presents a new approach and an accompanying open-source software toolbox that facilitates a robust integrative analysis for population structure and genomic ancestry estimates for heterogeneous datasets. Given that visually evident and easily recognizable patterns of human facial characteristics covary with genomic ancestry, we can generate predicted ancestry faces on both the population and individual levels as we illustrate for the 26 1000 Genome populations and for eight eminent ancient-DNA profiles, respectively.

genetics↗

bioRxiv2018

Liquid co-substrates repower sewage microbiomes

A range of parameters are known to shape the methanogenic communities of biogas-producing digesters and to strongly influence the amount of biogas produced. In this work, liquid and solid fractions of grass biomass were used separately for semicontinuous batch methanation using sewage sludge as seed sludge. During 6 months of incubation, the amount of input COD was increased gradually, and the underlying methanogenic microbiome was assessed by means of microscopy-based automated cell counting and full-length 16S rRNA high-throughput sequencing. In this sense, we prove for the first time the suitability of the ONTMinION platform as a monitoring tool for anaerobic digestion systems. According to our results, solid-fed batches were highly unstable at higher COD input concentrations, and kept Methanosaeta spp. typically associated to sewage sludge-as the majoritary methanogenic archaea. In contrast, liquid-fed batches developed a more stable microbiome, proved enriched in Methanosarcina spp, and resulted in higher methanogenic yield. This work demonstrates the high repowering potential of microbiomes from sewage sludge digesters, and highlight the effectiveness of liquefied substrates for increasing biogas productivity in anaerobic digestions.

microbiology↗

bioRxiv2017

Reply To Lazaridis And Reich: Robust Model-Based Inference Of Male-Biased Admixture During Bronze Age Migration From The Pontic-Caspian Steppe

Comparing the sex-specifically inherited X chromosome to the autosomes in ancient genetic samples, we (1) studied sex-specific admixture for two prehistoric migrations. For each migration, we used several admixture estimation procedures--including ADMIXTURE model-based clustering (2)--comparing X-chromosomal and autosomal ancestry in contemporaneous Central Europeans, and interpreting greater admixture from the migrating population on the autosomes as male-biased migration. For migration into late Neolithic/Bronze Age Central Europeans (\"BA\") from the Pontic-Caspian steppe (\"SP\"), we inferred male-biased admixture at 5-14 males per migrating female.\n\nLazaridis & Reich (3) contest this male-biased migration claim. For simulated individuals, they claim that ADMIXTURE provides biased X-chromosomal ancestry estimates. They argue that if the bias is taken into account, the ...

genetics↗

bioRxiv2017

Estimating genetic kin relationships in prehistoric populations

Archaeogenomic research has proven to be a valuable tool to trace migrations of historic and prehistoric individuals and groups, whereas relationships within a group or burial site have not been investigated to a large extent. Knowing the genetic kinship of historic and prehistoric individuals would give important insights into social structures of ancient and historic cultures. Most archaeogenetic research concerning kinship has been restricted to uniparental markers, while studies using genome-wide information were mainly focused on comparisons between populations. Applications which infer the degree of relationship based on modern-day DNA information typically require diploid genotype data. Low concentration of endogenous DNA, fragmentation and other post-mortem damage to ancient DNA (aDNA) makes the application of such tools unfeasible for most archaeological samples. To infer family relationships for degraded samples, we developed the software READ (Relationship Estimation from Ancient DNA). We show that our heuristic approach can successfully infer up to second degree relationships with as little as 0.1x shotgun coverage per genome for pairs of individuals. We uncover previously unknown relationships among prehistoric individuals by applying READ to published aDNA data from several human remains excavated from different cultural contexts. In particular, we find a group of five closely related males from the same Corded Ware culture site in modern-day Germany, suggesting patrilocality, which highlights the possibility to uncover social structures of ancient populations by applying READ to genome-wide aDNA data.

genetics↗