qpAdm is a statistical tool that is often used for testing large sets of alternative admixture models for a target population. Despite its popularity, qpAdm remains untested on 2D stepping stone landscapes and in situations with low prestudy odds (low ratio of true to false models). We tested high-throughput qpAdm protocols with typical properties such as number of source combinations per target, model complexity, model feasibility criteria, etc. Those protocols were applied to admixture graph-shaped and stepping stone simulated histories sampled randomly or systematically. We demonstrate that false discovery rates of high-throughput qpAdm protocols exceed 50% for many parameter combinations since: (1) prestudy odds are low and fall rapidly with increasing model complexity; (2) complex migration networks violate the assumptions of the method; hence, there is poor correlation between qpAdm P-values and model optimality, contributing to low but nonzero false-positive rate and low power; and (3) although admixture fraction estimates between 0 and 1 are largely restricted to symmetric configurations of sources around a target, a small fraction of asymmetric highly nonoptimal models have estimates in the same interval, contributing to the false-positive rate. We also reinterpret large sets of qpAdm models from 2 studies in terms of source-target distance and symmetry and suggest improvements to qpAdm protocols: (1) temporal stratification of targets and proxy sources in the case of admixture graph-shaped histories, (2) focused exploration of few models for increasing prestudy odds; and (3) dense landscape sampling for increasing power and stringent conditions on estimated admixture fractions for decreasing the false-positive rate.

• Klíčová slova
• qpAdm, admixture graphs, archaeogenetics, genetic admixture, simulation, stepping stone models,
• MeSH
• lidé MeSH
• modely genetické * MeSH
• populační genetika * metody   MeSH
• software * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

qpAdm is a statistical tool that is often used for testing large sets of alternative admixture models for a target population. Despite its popularity, qpAdm remains untested on two-dimensional stepping-stone landscapes and in situations with low pre-study odds (low ratio of true to false models). We tested high-throughput qpAdm protocols with typical properties such as number of source combinations per target, model complexity, model feasibility criteria, etc. Those protocols were applied to admixture-graph-shaped and stepping-stone simulated histories sampled randomly or systematically. We demonstrate that false discovery rates of high-throughput qpAdm protocols exceed 50% for many parameter combinations since: 1) pre-study odds are low and fall rapidly with increasing model complexity; 2) complex migration networks violate the assumptions of the method, hence there is poor correlation between qpAdm p-values and model optimality, contributing to low but non-zero false positive rate and low power; 3) although admixture fraction estimates between 0 and 1 are largely restricted to symmetric configurations of sources around a target, a small fraction of asymmetric highly non-optimal models have estimates in the same interval, contributing to the false positive rate. We also re-interpret large sets of qpAdm models from two studies in terms of source-target distance and symmetry and suggest improvements to qpAdm protocols: 1) temporal stratification of targets and proxy sources in the case of admixture-graph-shaped histories; 2) focused exploration of few models for increasing pre-study odds; 3) dense landscape sampling for increasing power and stringent conditions on estimated admixture fractions for decreasing the false positive rate.

• Klíčová slova
• admixture graphs, archaeogenetics, genetic admixture, qpAdm, simulation, stepping-stone models,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

Since the 1960s, more than 350,000 new chemicals have been introduced into the lives of humans and domestic animals. Many of them have become part of modern life and some are affecting nature as pollutants. Yet, our comprehension of their potential health risks for both humans and animals remains partial. The "epithelial barrier theory" suggests that genetic predisposition and exposure to diverse factors damaging the epithelial barriers contribute to the emergence of allergic and autoimmune conditions. Impaired epithelial barriers, microbial dysbiosis, and tissue inflammation have been observed in a high number of mucosal inflammatory, autoimmune and neuropsychiatric diseases, many of which showed increased prevalence in the last decades. Pets, especially cats and dogs, share living spaces with humans and are exposed to household cleaners, personal care products, air pollutants, and microplastics. The utilisation of cosmetic products and food additives for pets is on the rise, unfortunately, accompanied by less rigorous safety regulations than those governing human products. In this review, we explore the implications of disruptions in epithelial barriers on the well-being of companion animals, drawing comparisons with humans, and endeavour to elucidate the spectrum of diseases that afflict them. In addition, future research areas with the interconnectedness of human, animal, and environmental well-being are highlighted in line with the "One Health" concept.

• Klíčová slova
• companion animals, epigenetics, epithelial barrier, exposome, microbiota, skin,
• MeSH
• domácí zvířata * imunologie   MeSH
• epitel imunologie   MeSH
• kočky MeSH
• lidé MeSH
• psi MeSH
• vystavení vlivu životního prostředí škodlivé účinky   MeSH
• zvířata MeSH
• Check Tag
• kočky MeSH
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

Our knowledge of human evolutionary history has been greatly advanced by paleogenomics. Since the 2020s, the study of ancient DNA has increasingly focused on reconstructing the recent past. However, the accuracy of paleogenomic methods in resolving questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation remains an open question. We evaluated the performance and behavior of two commonly used methods, qpAdm and the f3-statistic, on admixture inference under a diversity of demographic models and data conditions. We performed two complementary simulation approaches-firstly exploring a wide demographic parameter space under four simple demographic models of varying complexities and configurations using branch-length data from two chromosomes-and secondly, we analyzed a model of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudohaploidization. We observe that population differentiation is the primary factor driving qpAdm performance. Notably, while complex gene flow histories influence which models are classified as plausible, they do not reduce overall performance. Under conditions reflective of the historical period, qpAdm most frequently identifies the true model as plausible among a small candidate set of closely related populations. To increase the utility for resolving fine-scaled hypotheses, we provide a heuristic for further distinguishing between candidate models that incorporates qpAdm model P-values and f3-statistics. Finally, we demonstrate a significant performance increase for qpAdm using whole-genome branch-length f2-statistics, highlighting the potential for improved demographic inference that could be achieved with future advancements in f-statistic estimations.

• Klíčová slova
• f-statistics, aDNA, admixture, ancient DNA, archaeogenetics, paleogenomics, qpAdm,
• MeSH
• demografie MeSH
• genomika * metody   MeSH
• modely genetické MeSH
• paleontologie * metody   MeSH
• software MeSH
• správnost dat MeSH
• Publikační typ
• časopisecké články MeSH

Antler is one of the primary animal raw materials exploited for technical purposes by the hunter-gatherer groups of the Eurasian Upper Palaeolithic (UP) all over the ecological range of deers, and beyond. It was exhaustively employed to produce one of the most critical tools for the survival of the UP societies: hunting weapons. However, antler implements can be made from diverse deer taxa, with different ecological requirements and ethological behaviours. Identifying the antler's origin at a taxonomic level is thus essential in improving our knowledge of humans' functional, practical and symbolic choices, as well as the human-animal interface during Prehistoric times. Nevertheless, palaeogenetics analyses have focused mainly on bone and teeth, with genetic studies of antler generally focused on modern deer conservation. Here we present the results of the first whole mitochondrial genome ancient DNA (aDNA) analysis by means of in-solution hybridisation capture of antlers from pre-Holocene archaeological contexts. We analysed a set of 50 Palaeolithic and Neolithic (c. 34-8ka) antler and osseous objects from South-Western Europe, Central Europe, South-Western Asia and the Caucasus. We successfully obtained aDNA, allowing us to identify the exploited taxa and demonstrate the archaeological relevance of those finds. Moreover, as most of the antlers were sampled using a minimally-invasive method, further analyses (morphometric, technical, genetic, radiometric and more) remain possible on these objects.

• Klíčová slova
• Ancient DNA, Antler, Hunting implements, Osseous tools, Upper palaeolithic,
• Publikační typ
• časopisecké články MeSH

Paleogenomics has expanded our knowledge of human evolutionary history. Since the 2020s, the study of ancient DNA has increased its focus on reconstructing the recent past. However, the accuracy of paleogenomic methods in answering questions of historical and archaeological importance amidst the increased demographic complexity and decreased genetic differentiation within the historical period remains an open question. We used two simulation approaches to evaluate the limitations and behavior of commonly used methods, qpAdm and the f3-statistic, on admixture inference. The first is based on branch-length data simulated from four simple demographic models of varying complexities and configurations. The second, an analysis of Eurasian history composed of 59 populations using whole-genome data modified with ancient DNA conditions such as SNP ascertainment, data missingness, and pseudo-haploidization. We show that under conditions resembling historical populations, qpAdm can identify a small candidate set of true sources and populations closely related to them. However, in typical ancient DNA conditions, qpAdm is unable to further distinguish between them, limiting its utility for resolving fine-scaled hypotheses. Notably, we find that complex gene-flow histories generally lead to improvements in the performance of qpAdm and observe no bias in the estimation of admixture weights. We offer a heuristic for admixture inference that incorporates admixture weight estimate and P-values of qpAdm models, and f3-statistics to enhance the power to distinguish between multiple plausible candidates. Finally, we highlight the future potential of qpAdm through whole-genome branch-length f2-statistics, demonstrating the improved demographic inference that could be achieved with advancements in f-statistic estimations.

• Klíčová slova
• aDNA, admixture, archaeogenetics, f-statistics, paleogenomics, qpAdm,
• Publikační typ
• časopisecké články MeSH
• preprinty MeSH

f-statistics have emerged as a first line of analysis for making inferences about demographic history from genome-wide data. Not only are they guaranteed to allow robust tests of the fits of proposed models of population history to data when analyzing full genome sequencing data-that is, all single nucleotide polymorphisms (SNPs) in the individuals being analyzed-but they are also guaranteed to allow robust tests of models for SNPs ascertained as polymorphic in a population that is an outgroup in a phylogenetic sense to all groups being analyzed. True "outgroup ascertainment" is in practice impossible in humans because our species has arisen from a substructured ancestral population that does not descend from a homogeneous ancestral population going back many hundreds of thousands of years into the past. However, initial studies suggested that non-outgroup-ascertainment schemes might produce robust enough results using f-statistics, and that motivated widespread fitting of models to data using non-outgroup-ascertained SNP panels such as the "Affymetrix Human Origins array" which has been genotyped on thousands of modern individuals from hundreds of populations, or the "1240k" in-solution enrichment reagent which has been the source of about 70% of published genome-wide data for ancient humans. In this study, we show that while analyses of population history using such panels work well for studies of relationships among non-African populations and one African outgroup, when co-modeling more than one sub-Saharan African and/or archaic human groups (Neanderthals and Denisovans), fitting of f-statistics to such SNP sets is expected to frequently lead to false rejection of true demographic histories, and failure to reject incorrect models. Analyzing panels of SNPs polymorphic in archaic humans, which has been suggested as a solution for the ascertainment problem, has limited statistical power and retains important biases. However, by carrying out simulations of diverse demographic histories, we show that bias in inferences based on f-statistics can be minimized by ascertaining on variants common in a union of diverse African groups; such ascertainment retains high statistical power while allowing co-analysis of archaic and modern groups.

• MeSH
• Afričané * genetika   MeSH
• biologická variabilita populace genetika   MeSH
• černoši genetika   MeSH
• demografie * dějiny   MeSH
• fylogeneze * MeSH
• genotyp MeSH
• jednonukleotidový polymorfismus * genetika   MeSH
• lidé MeSH
• mapování chromozomů MeSH
• neandertálci genetika   MeSH
• statistické modely MeSH
• zkreslení výsledků (epidemiologie) MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The Sicilian wolf remained isolated in Sicily from the end of the Pleistocene until its extermination in the 1930s-1960s. Given its long-term isolation on the island and distinctive morphology, the genetic origin of the Sicilian wolf remains debated. We sequenced four nuclear genomes and five mitogenomes from the seven existing museum specimens to investigate the Sicilian wolf ancestry, relationships with extant and extinct wolves and dogs, and diversity. Our results show that the Sicilian wolf is most closely related to the Italian wolf but carries ancestry from a lineage related to European Eneolithic and Bronze Age dogs. The average nucleotide diversity of the Sicilian wolf was half of the Italian wolf, with 37-50% of its genome contained in runs of homozygosity. Overall, we show that, by the time it went extinct, the Sicilian wolf had high inbreeding and low-genetic diversity, consistent with a population in an insular environment.

• Klíčová slova
• Canine genetics, Evolutionary biology,
• Publikační typ
• časopisecké články MeSH

Our understanding of population history in deep time has been assisted by fitting admixture graphs (AGs) to data: models that specify the ordering of population splits and mixtures, which along with the amount of genetic drift and the proportions of mixture, is the only information needed to predict the patterns of allele frequency correlation among populations. The space of possible AGs relating populations is vast, and thus most published studies have identified fitting AGs through a manual process driven by prior hypotheses, leaving the majority of alternative models unexplored. Here, we develop a method for systematically searching the space of all AGs that can incorporate non-genetic information in the form of topology constraints. We implement this findGraphs tool within a software package, ADMIXTOOLS 2, which is a reimplementation of the ADMIXTOOLS software with new features and large performance gains. We apply this methodology to identify alternative models to AGs that played key roles in eight publications and find that in nearly all cases many alternative models fit nominally or significantly better than the published one. Our results suggest that strong claims about population history from AGs should only be made when all well-fitting and temporally plausible models share common topological features. Our re-evaluation of published data also provides insight into the population histories of humans, dogs, and horses, identifying features that are stable across the models we explored, as well as scenarios of populations relationships that differ in important ways from models that have been highlighted in the literature.

• Klíčová slova
• admixture graphs, dogs, evolutionary biology, f-statistics, genetics, genomics, horses, human, humans, population genetics,
• MeSH
• frekvence genu MeSH
• genetický drift MeSH
• Hominidae * MeSH
• koně MeSH
• lidé MeSH
• modely genetické MeSH
• populační genetika * MeSH
• psi MeSH
• software MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• psi MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH