Biology subjects

Nickel, B.

Publications and source records attributed to Nickel, B..

6 recordsLinked to original sources

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↗

bioRxiv2025

The origin and molecular evolution of the mammalian liver cell architecture

The liver is a central organ with essential roles in processes such as nutritional metabolism, detoxification, and immune defense1-6. It has been instrumental in the adaptation of mammalian species to diverse environments, as reflected by its rapid molecular evolution7,8. However, the origins and evolutionary dynamics of liver cell types and their structural organization remain largely unexplored. Here we report evolutionary analyses of transcriptome and chromatin accessibility data for liver cells from 17 species, spanning all major feeding strategies (herbivory, omnivory, carnivory, insectivory), great apes (including humans), placental clades (Afrotheria, Xenarthra, Laurasiatheria, Euarchontoglires), major mammalian lineages (placentals, marsupials, monotremes), and a bird as outgroup. Integrated with spatial transcriptomics, our data reveal that liver zonation--the compartmentalization of hepatocyte functions along the lobule, the livers fundamental anatomical and functional unit--is conserved across mammals but absent in other vertebrates. We find that zonation originated in the mammalian ancestor, driven by the emergence of WNT and R-spondin signaling from central vein endothelial cells, which activate central hepatocyte gene expression via the transcription factor TCF7L2. Despite this conserved architecture and signaling, genes with zonated expression exhibit rapid evolutionary turnover. Consistently, hepatocytes evolve fast, likely due to reduced selective constraints, enabling adaptive changes under positive selection. Alongside immune cells, hepatocytes are therefore key drivers of the livers rapid evolution and functional innovations. In great apes, we identify human-specific shifts in zonation and cell-type-specific expression linked to recent cis-regulatory changes, particularly in genes involved in lipid metabolism, likely contributing to human-specific metabolic traits. Our study uncovers the origins of a mammal-specific liver cell architecture, within which reduced constraints facilitated molecular changes underlying ecological adaptations.

evolutionary biology↗

bioRxiv2022

3D printed SAXS chamber for controlled in-situ dialysis and optical characterization

3D printing changes the scope of how samples can be mounted for small angle X-ray scattering (SAXS). In this paper we present a 3D printed X-ray chamber, which allows for in-situ exchange of buffer and in-situ optical transmission spectroscopy. The chamber is made of cyclic olefin copolymers (COC), including COC X-ray windows providing ultra low SAXS background. The design integrates a membrane insert for in-situ dialysis of the 100 {micro}l sample volume against a reservoir, which enables measurements of the same sample under multiple conditions using an in-house X-ray setup equipped with a 17.4 keV molybdenum source. We demonstrate the designs capabilities by measuring reversible structural changes in lipid and polymer systems as a function of salt concentration and pH. In the same chambers optical light transmission spectroscopy was carried out measuring optical turbidity of the mesophases and local pH values using pH-responsive dyes. Microfluidic exchange and optical spectroscopy combined with in-situ X-ray scattering enables vast applications for the study of responsive materials.

biophysics↗

bioRxiv2022

Trypanosoma brucei: A novel system for metacyclogenesis and complete cyclical development in vitro

We describe an in vitro system that allows metacyclogenesis of T. brucei ssp. and is not restricted to certain parasite lines. Following the work of Hirumi and co-workers we developed a modified in vitro system which allows metacyclogenesis within 7 to 20 days. The most striking changes were the addition of citrate and cis-aconitate, which triggers transformation from bloodstream to procyclic forms, and the elimination of the remaining bloodstream forms by salicylhydroxamic acid and glycerol. A positive feature of this system is that T. b. gambiense samples isolated from patients, and transformed to procyclic forms for transport, could give rise to infective forms that could be passaged in rodents.

microbiology↗

bioRxiv2020

Denisovan ancestry and population history of early East Asians

We present analyses of the genome of a ~34,000-year-old hominin skull cap discovered in the Salkhit Valley in North East Mongolia. We show that this individual was a female member of a modern human population that, following the split between East and West Eurasians, experienced substantial gene flow from West Eurasians. Both she and a 40,000-year-old individual from Tianyuan outside Beijing carried genomic segments of Denisovan ancestry. These segments derive from the same Denisovan admixture event(s) that contributed to present-day mainland Asians but are distinct from the Denisovan DNA segments in present-day Papuans and Aboriginal Australians.

evolutionary biology↗

bioRxiv2018

Historical biogeography of the leopard (Panthera pardus) and its extinct Eurasian populations

BackgroundResolving the historical biogeography of the leopard (Panthera pardus) is a complex issue, because patterns inferred from fossils and from molecular data lack congruence. Fossil evidence supports an African origin, and suggests that leopards were already present in Eurasia during the Early Pleistocene. Analysis of DNA sequences however, suggests a more recent, Middle Pleistocene shared ancestry of Asian and African leopards. These contrasting patterns led researchers to propose a two-stage hypothesis of leopard dispersal out of Africa: an initial Early Pleistocene colonisation of Asia and a subsequent replacement by a second colonisation wave during the Middle Pleistocene. The status of Late Pleistocene European leopards within this scenario is unclear: were these populations remnants of the first dispersal, or do the last surviving European leopards share more recent ancestry with their African counterparts?\n\nResultsIn this study, we generate and analyse mitogenome sequences from historical samples that span the entire modern leopard distribution, as well as from Late Pleistocene remains. We find a deep bifurcation between African and Eurasian mitochondrial lineages ([~]710 Ka), with the European ancient samples as sister to all Asian lineages ([~]483 Ka). The modern and historical mainland Asian lineages share a relatively recent common ancestor ([~]122 Ka), and we find one Javan sample nested within these.\n\nConclusionsThe phylogenetic placement of the ancient European leopard as sister group to Asian leopards suggests that these populations originate from the same out-of-Africa dispersal which founded the Asian lineages. The coalescence time found for the mitochondrial lineages aligns well with the earliest undisputed fossils in Eurasia, and thus encourages a re-evaluation of the identification of the much older putative leopard fossils from the region. The relatively recent ancestry of all mainland Asian leopard lineages suggests that these populations underwent a severe population bottleneck during the Pleistocene. Finally, although only based on a single sample, the unexpected phylogenetic placement of the Javan leopard could be interpreted as evidence for exchange of mitochondrial lineages between Java and mainland Asia, calling for further investigation into the evolutionary history of this subspecies.

evolutionary biology↗