Biology subjects

Skov, L.

Publications and source records attributed to Skov, L..

15 recordsLinked to original sources

bioRxiv2026

No signal of a super-archaic origin of the Denisovan AMBN gene, a comment on the protein affinity of Homo erectus and Denisovan enamel proteins.

Homo erectus is a species that occupies a central role in the study of human evolution. To investigate its taxonomic identity, Fu et al. 2026 extracted and sequenced enamel proteins from 6 fossils assigned to Homo erectus, originating from 3 localities in China and dated to around 400 thousand years ago. Unexpectedly, all samples possess an amino acid variant on the enamel protein ameloblastin (AMBN) which is uniquely shared with more recent Denisovan fossils and a subset of present day humans who are known to carry introgressed Denisovan ancestry. The samples also showcase an additional, novel variant on the same enamel protein. To explain this result, Fu et al. 2026 propose a model where the sampled Homo erectus population (or its recent ancestors) interbred with later arriving Denisovans, introducing one of the two AMBN variants into the Denisovan population. While this model fits our overall understanding of the interactions between these archaic populations, it rests on the assumption that the Denisovan AMBN variant has an archaic, Homo erectus-like, source. Here we show that the AMBN gene of late Denisovans has no signal of introgression from a super-archaic source, making the suggested model unlikely for this gene. We also show that the AMBN gene of Denisova 25, an earlier Denisova, does show a signal of introgression, but one that better matches Neanderthals and modern humans, rather than a super-archaic source. We propose a number of alternative models that could help explain the observed affinity between the sampled H. erectus and Denisovans without requiring the introgression of AMBN from an archaic source into Denisovans. We discuss their strengths and weaknesses and how new data could help resolve them.

evolutionary biology↗

bioRxiv2026

Immunopeptidomics reveals peptide antigens preferentially presented in psoriasis lesional skin of HLA-C*06:02 carriers

BackgroundHuman leukocyte antigen (HLA)-C*06:02 is a major genetic risk factor for psoriasis and understanding the HLA-C*06:02-presented peptide antigen repertoire (immunopeptidome) in the skin of patients is crucial for identifying autoantigens. Yet, no skin immunopeptidome data from patients stratified by their HLA-C*06:02 status exists. ObjectiveWe analysed biopsies from lesional and non-lesional skin of patients with psoriasis vulgaris (n=12), guttate psoriasis (n=8), or from skin of healthy controls (n=16). MethodsHLA class I and class II peptide complexes were isolated by serial immunoprecipitation and HLA-bound peptides identified by liquid chromatography-tandem mass spectrometry. HLA-C*06:02 genotyping was performed by polymerase chain reaction. ResultsOver 99,000 non-redundant peptide ligands were identified across all samples. Substantially more HLA class I and class II peptides were detected in lesional psoriatic skin compared to matched non-lesional and healthy skin. Three peptides predicted to bind HLA-C*06:02, including MRASSFLIV from the known psoriasis marker peptidase inhibitor 3 (PI3), were identified in all lesions of HLA-C*06:02-positive patients but were rarely detected or absent in HLA-C*06:02-negative patient lesional skin and not detected at all in unaffected skin. Keratinocyte differentiation-associated protein (KRTDAP) was a notable source of lesion-specific HLA class II ligands contributing three out of six peptides detected in more than half of the lesional samples. ConclusionActive psoriatic lesions display an altered and expanded immunopeptidome compared to unaffected skin. We have identified numerous unreported, lesion-specific HLA-bound peptides and their source proteins. These findings offer insights into the pathobiology of psoriasis and provide a resource for future functional studies. CAPSULE SUMMARYA selection of immunopeptides is presented exclusively in lesional skin of HLA-C*06:02+ patients with psoriasis that may represent antigenic drivers of disease.

immunology↗

bioRxiv2025

Enhancement of hidden Markov model analyses for improved inference of archaic introgression in modern humans

Insights into the admixture history between modern and archaic humans require accurately inferred introgressed fragments within modern genomes. Here, we introduce two enhancements to hidden Markov models (HMMs) implemented in hmmix. First, we develop a method for sampling hidden state sequences conditional on observed genomic data, enabling robust estimation of admixture summary statistics--such as admixture proportion and fragment length distributions. This represents an improvement compared to relying solely on point estimates as provided by classical decoding methods. Additionally, we integrate the Finite Markov Chain Imbedding (FMCI) framework, allowing exact analytical calculation of these admixture statistics, tailored to large scale human genomes. Second, we implement a novel hybrid decoding method which combines the strengths of Viterbi and Posterior decoding methods, substantially improving the reliability of archaic fragments identified. We validate these improvements on data from the 1000 Genomes Project and demonstrate that our sampling method yield more accurate admixture estimates from single individuals compared to existing approaches requiring extensive population-level datasets. Moreover we show how hybrid decoding can be instrumental in resolving the inference of local archaic haplotype structure in modern human genomes. These methodological advancements broadly enhance HMM-based analyses and will provide deeper insight into the complex history of genetic interactions between archaic and modern human populations.

evolutionary biology↗

bioRxiv2024

Himalayan whole-genome sequences provide insight into population formation and adaptation

High-altitude environments pose substantial challenges for human survival and reproduction, attracting considerable attention to the demographic and adaptive histories of high-altitude populations. Previous work focused mainly on Tibetans, establishing their genetic relatedness to East Asians and their genetic adaptation to high altitude, especially at EPAS1. Here, we present 87 new whole-genome sequences from 16 Himalayan populations and the insight they provide into the genomic history of the region. We show that population structure in the Himalayas began to emerge as early as 10,000 years ago, predating archaeological evidence of permanent habitation above 2,500 meters by approximately 6,000 years. The high prevalence of the introgressed adaptive EPAS1 haplotype in all high-altitude populations today supports a shared genetic origin and its importance for survival in this region. We also identify additional selection signals in genes associated with hypoxia, physical activity, immunity and metabolism which could have facilitated adaptation to the harsh environment. Over time, increasing genetic structure led to the diverse and strongly differentiated ethnic groups observed today, most of which maintained small population sizes throughout their history or experienced severe bottlenecks. Between 6,000 and 3,000 years ago, a few uniparental lineages became predominant, likely coinciding with the advent of agriculture, although significant population growth was not observed in the Himalayas except in the Tibetans. In more recent times, we detect bidirectional gene flow between high-altitude and lowland groups, occurring on both sides of the Himalayan range. The timing of this admixture aligns with the rise and expansion of historical regional powers, particularly during the Tibetan Empire and the northern Indian Gupta Empire. In the past few centuries, migrations to the Himalayas seem to have occurred alongside conflicts and population displacements in nearby regions and show some sex bias.

genomics↗

bioRxiv2024

Neandertal ancestry through time: Insights from genomes of ancient and present-day humans

Gene flow from Neandertals has shaped the landscape of genetic and phenotypic variation in modern humans. We identify the location and size of introgressed Neandertal ancestry segments in more than 300 genomes spanning the last 50,000 years. We study how Neandertal ancestry is shared among individuals to infer the time and duration of the Neandertal gene flow. We find the correlation of Neandertal segment locations across individuals and their divergence to sequenced Neandertals, both support a model of single major Neandertal gene flow. Our catalog of introgressed segments through time confirms that most natural selection-positive and negative-on Neandertal ancestry variants occurred immediately after the gene flow, and provides new insights into how the contact with Neandertals shaped human origins and adaptation.

evolutionary biology↗

bioRxiv2024

50,000 years of Evolutionary History of India: Insights from ~2,700 Whole Genome Sequences

India has been underrepresented in whole genome sequencing studies. We generated 2,762 high coverage genomes from India--including individuals from most geographic regions, speakers of all major languages, and tribal and caste groups--providing a comprehensive survey of genetic variation in India. With these data, we reconstruct the evolutionary history of India through space and time at fine scales. We show that most Indians derive ancestry from three ancestral groups related to ancient Iranian farmers, Eurasian Steppe pastoralists and South Asian hunter-gatherers. We uncover a common source of Iranian-related ancestry from early Neolithic cultures of Central Asia into the ancestors of Ancestral South Indians (ASI), Ancestral North Indians (ANI), Austro-asiatic-related and East Asian-related groups in India. Following these admixtures, India experienced a major demographic shift towards endogamy, resulting in extensive homozygosity and identity-by-descent sharing among individuals. At deep time scales, Indians derive around 1-2% of their ancestry through gene flow from archaic hominins, Neanderthals and Denisovans. By assembling the surviving fragments of archaic ancestry in modern Indians, we recover [~]1.5 Gb (or 50%) of the introgressing Neanderthal and [~]0.6 Gb (or 20%) of the introgressing Denisovan genomes, more than any other previous archaic ancestry study. Moreover, Indians have the largest variation in Neanderthal ancestry, as well as the highest amount of population-specific Neanderthal segments among worldwide groups. Finally, we demonstrate that most of the genetic variation in Indians stems from a single major migration out of Africa that occurred around 50,000 years ago, with minimal contribution from earlier migration waves. Together, these analyses provide a detailed view of the population history of India and underscore the value of expanding genomic surveys to diverse groups outside Europe.

evolutionary biology↗

bioRxiv2022

Extraordinary selection on the human X chromosome associated with archaic admixture

The X chromosome in non-African human populations shows less diversity and less Neanderthal introgression than expected under the standard neutral model. We analyzed 162 X chromosomes from human males worldwide and discovered 14 chromosomal regions where haplotypes of several hundred kilobases rapidly rose to high frequencies in non-Africans. These observations cannot be explained by neutral genetic drift in realistic demographic scenarios and are only consistent with partial selective sweeps produced by strong selection. Using an approach for inferring individual Neanderthal-derived haplotypes, which do not rely on an archaic reference genome, we further discover that the swept haplotypes are devoid of the archaic ancestry otherwise typical of the affected chromosomal regions. The ancient Ust-Ishim male carries its expected proportion of these haplotypes, implying that the sweeps must have occurred between 45,000 and 55,000 years ago. Finally, we find that the chromosomal positions of sweeps overlap previously reported hotspots of selection in great ape evolution. We propose that this puzzling combination of observations points to a general mechanism of positive selection unique to the X chromosome.

evolutionary biology↗

bioRxiv2021

Different historical generation intervals in human populations inferred from Neanderthal fragment lengths and patterns of mutation accumulation

After the main out-of-Africa event, humans interbred with Neanderthals leaving 1-2% of Neanderthal DNA scattered in small fragments in all non-African genomes today1,2. Here we investigate the size distribution of these fragments in non-African genomes3. We find consistent differences in fragment length distributions across Eurasia with 11% longer fragments in East Asians than in West Eurasians. By comparing extant populations and ancient samples, we show that these differences are due to a different rate of decay in length by recombination since the Neanderthal admixture. In line with this, we observe a strong correlation between the average fragment length and the accumulation of derived mutations, similar to what is expected by changing the ages at reproduction as estimated from trio studies4. Altogether, our results suggest consistent differences in the generation interval across Eurasia, by up to 20% (e.g. 25 versus 30 years), over the past 40,000 years. We use sex-specific accumulations of derived alleles to infer how these changes in generation intervals between geographical regions could have been mainly driven by shifts in either male or female age of reproduction, or both. We also find that previously reported variation in the mutational spectrum5 may be largely explained by changes to the generation interval and not by changes to the underlying mutational mechanism. We conclude that Neanderthal fragment lengths provide unique insight into differences of a key demographic parameter among human populations over the recent history.

evolutionary biology↗

bioRxiv2020

Spatially and cell-type resolved quantitative proteomic atlas of healthy human skin

Human skin provides both physical integrity and immunological protection from the external environment using functionally distinct layers, cell types and extracellular matrix. Despite its central role in human health and disease, the constituent proteins of skin have not been systematically characterized. Here, we combined advanced tissue dissection methods, flow cytometry and state-of-the-art proteomics to describe a spatially-resolved quantitative proteomic atlas of human skin. We quantified 10,701 proteins as a function of their spatial location and cellular origin. The resulting protein atlas and our initial data analyses demonstrate the value of proteomics for understanding cell-type diversity within the skin. We describe the quantitative distribution of structural proteins, known and novel proteins specific to cellular subsets and those with specialized immunological functions such as cytokines and chemokines. We anticipate that this proteomic atlas of human skin will become an essential community resource for basic and translational research (www.skin.science).

cell biology↗

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↗

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

Strong selective sweeps before 45,000BP displaced archaic admixture across the human X chromosome

The X chromosome in non-African populations has less diversity and less Neanderthal introgression than expected. We analyzed X chromosome diversity across the globe and discovered seventeen chromosomal regions, where haplotypes of several hundred kilobases have recently reached high frequencies in non-African populations only. The selective sweeps must have occurred more than 45,000 years ago because the ancient Ust-Ishim male also carries its expected proportion of these haplotypes. Surprisingly, the swept haplotypes are entirely devoid of Neanderthal introgression, which implies that a population without Neanderthal admixture contributed the swept haplotypes. It also implies that the sweeps must have happened after the main interbreeding event with Neanderthals about 55,000 BP. These swept haplotypes may thus be the only genetic remnants of an earlier out-of-Africa event.\n\nOne Sentence SummaryAfter humans expanded out of Africa, the X chromosome experienced a burst of extreme natural selection that removed Neanderthal admixture.

genomics↗

bioRxiv2018

Detecting archaic introgression without archaic reference genomes

Human populations out of Africa have experienced at least two bouts of introgression from archaic humans, from Neanderthals and Denisovans. In Papuans there is prior evidence of both these introgressions. Here we present a new approach to detect segments of individual genomes of archaic origin without using an archaic reference genome. The approach is based on a hidden Markov model that identifies genomic regions with a high density of single nucleotide variants (SNVs) not seen in unadmixed populations. We show using simulations that this provides a powerful approach to identifying segments of archaic introgression with a small rate of false detection. Furthermore our approach is able to accurately infer admixture proportions and divergence time of human and archaic populations.\n\nWe apply the model to detect archaic introgression in 89 Papuans and show how the identified segments can be assigned to likely Neanderthal or Denisovan origin. We report more Denisovan admixture than previous studies and directly find a shift in size distribution of fragments of Neanderthal and Denisovan origin that is compatible with a difference in admixture time. Furthermore, we identify small amounts of Denisova ancestry in West Eurasians, South East Asians and South Asians.

evolutionary biology↗

bioRxiv2017

Dynamic copy number evolution of X- and Y-linked ampliconic genes in human populations

Ampliconic genes are good candidates for speciation genes: they are testis-expressed, multicopy and localized on sex chromosomes. Moreover, copy number variation in a specific ampliconic gene pair (Slx and Sly) is involved in hybrid incompatibilities between M. musculus and M. domesticus. However, we know little about the distribution of the ampliconic genes copy number and their turnover in human populations. Here we explore the evolution of human X- and Y-linked ampliconic genes by investigating copy number variation (CNV) and coding variation between populations using the Simons Genome Diversity Project. We develop a method to assess CNVs using the read-depth on modified X and Y chromosome targets containing only one repetition of each ampliconic gene. Our results reveal extensive standing variation in copy number both within and between human populations for several ampliconic genes. For the Y chromosome, we can infer multiple independent amplifications and losses of these gene copies even within closely related Y haplogroups, that diversified less than 50,000 years ago. For the X chromosome, we also find high copy number and coding diversity within populations. While we cannot rule out that neutral processes are at the origin of this high diversity, this study gives insights on the distribution of copy number within human populations, and demonstrates an extremely fast turnover in copy number of these regions.

evolutionary biology↗

bioRxiv2017

Natural selection interacts with the local recombination rate to shape the evolution of hybrid genomes

While hybridization between species is increasingly appreciated to be a common occurrence, little is known about the forces that govern the subsequent evolution of hybrid genomes. We considered this question in three independent, naturally-occurring hybrid populations formed between swordtail fish species Xiphophorus birchmanni and X. malinche. To this end, we built a fine-scale genetic map and inferred patterns of local ancestry along the genomes of 690 individuals sampled from the three populations. In all three cases, we found hybrid ancestry to be more common in regions of high recombination and where there is linkage to fewer putative targets of selection. These same patterns are also apparent in a reanalysis of human-Neanderthal admixture. Our results lend support to models in which ancestry from the \"minor\" parental species persists only where it is rapidly uncoupled from alleles that are deleterious in hybrids, and show the retention of hybrid ancestry to be at least in part predictable from genomic features. Our analyses further indicate that in swordtail fish, the dominant source of selection on hybrids stems from deleterious combinations of epistatically-interacting alleles.\n\nOne sentence summaryThe persistence of hybrid ancestry is predictable from local recombination rates, in three replicate hybrid populations as well as in humans.

evolutionary biology↗