Felix Key

Felix Key

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Publications (67)
Preprint
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Zoonoses are among the greatest threats to human health, with many zoonotic pathogens believed to have emerged during prehistory. Palaeomicrobiological investigations of the zooarchaeological record hold potential to uncover the reservoirs, host ranges, and host adaptations of zoonotic pathogens but face challenges in identifying promising specimen...
Preprint
Full-text available
Most human pathogens are of zoonotic origin. Many emerged during prehistory, coinciding with domestication providing more opportunities for spillover from original host species. However, we lack direct evidence linking past animal reservoirs and human infections. Here we present a Yersinia pestis genome recovered from a 3rd millennium BCE domestica...
Article
Full-text available
Brucella melitensis is a major livestock bacterial pathogen and zoonosis, causing disease and infection-related abortions in small ruminants and humans. A considerable burden to animal-based economies today, the presence of Brucella in Neolithic pastoral communities has been hypothesised but we lack direct genomic evidence thus far. We report a 3.4...
Poster
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Cutaneous mast cells are closely associated anatomically with unmyelinated nerves and some neuropeptides induce mast cell degranulation. There is experimental evidence in rodent models that psychological stress can induce mast cell degranulation and a number of in-flammatory skin diseases in humans, including rosacea, psoriasis and atopic dermatiti...
Article
Full-text available
The opportunistic pathogen Staphylococcus aureus frequently colonizes the inflamed skin of people with atopic dermatitis (AD) and worsens disease severity by promoting skin damage. Here, we show, by longitudinally tracking 23 children treated for AD, that S. aureus adapts via de novo mutations during colonization. Each patient's S. aureus populatio...
Article
Full-text available
Significance The bacterium Yersinia pestis has caused numerous historically documented outbreaks of plague and research using ancient DNA could demonstrate that it already affected human populations during the Neolithic. However, the pathogen’s genetic diversity, geographic spread, and transmission dynamics during this early period of Y. pestis evo...
Article
Full-text available
Background Atopic dermatitis (AD) is characterized by an altered skin microbiome dominantly colonized by S. aureus. Standard treatment includes emollients, anti-inflammatory medications and antiseptics. Objectives To characterize changes in the skin microbiome during treatment for AD. Methods The skin microbiomes of children with moderate-to-seve...
Article
Full-text available
Salmonella enterica (S. enterica) has infected humans for a long time, but its evolutionary history and geographic spread across Eurasia is still poorly understood. Here, we screened for pathogen DNA in 14 ancient individuals from the Bronze Age Quanergou cemetery (XBQ), Xinjiang, China. In 6 individuals we detected S. enterica. We reconstructed S....
Article
Full-text available
Pathogens and associated outbreaks of infectious disease exert selective pressure on human populations, and any changes in allele frequencies that result may be especially evident for genes involved in immunity. In this regard, the 1346-1353 Yersinia pestis-caused Black Death pandemic, with continued plague outbreaks spanning several hundred years,...
Preprint
Full-text available
Bacteria acquire adaptive mutations during infections and within healthy microbiomes ¹⁻⁴ , but the potential of bacterial mutations to impact disease is not well understood. The inflamed skin of people with atopic dermatitis (AD) is heavily colonized with Staphylococcus aureus , an opportunistic pathogen associated with both asymptomatic colonizati...
Article
Full-text available
It has been hypothesized that the Neolithic transition towards an agricultural and pastoralist economy facilitated the emergence of human-adapted pathogens. Here, we recovered eight Salmonella enterica subsp. enterica genomes from human skeletons of transitional foragers, pastoralists and agropastoralists in western Eurasia that were up to 6,500 yr...
Article
Full-text available
Abstract High-throughput DNA sequencing enables large-scale metagenomic analyses of complex biological systems. Such analyses are not restricted to present-day samples and can also be applied to molecular data from archaeological remains. Investigations of ancient microbes can provide valuable information on past bacterial commensals and pathogens,...
Article
Full-text available
The second plague pandemic, caused by Yersinia pestis, devastated Europe and the nearby regions between the 14th and 18th centuries AD. Here we analyse human remains from ten European archaeological sites spanning this period and reconstruct 34 ancient Y. pestis genomes. Our data support an initial entry of the bacterium through eastern Europe, the...
Preprint
Full-text available
High-throughput DNA sequencing enables large-scale metagenomic analyses of complex biological systems. Such analyses are not restricted to present day environmental or clinical samples, but can also be fruitfully applied to molecular data from archaeological remains (ancient DNA), and a focus on ancient bacteria can provide valuable information on...
Article
Full-text available
Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes (gene diversity) was found in exome sequences of three Neandertals. Reduced gene diversity, particularly in genes involved in immunity...
Preprint
Full-text available
Genome-wide analyses of two Neandertals and a Denisovan have shown that these archaic humans had lower genetic heterozygosity than present-day people. A similar reduction in genetic diversity of protein-coding genes ( gene diversity ) was found in exome sequences of three Neandertals. Reduced gene diversity, and particularly in genes involved in im...
Article
Full-text available
The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one...
Data
Multiple sequence alignment of the 493 representative and five ancient HBV genomes. The multiple sequence alignment was stripped of any sites that had gaps in more than 95%.
Data
Number of reads mapping against the references shown in Supplementary file 1 before and after duplicate removal.
Data
Number of contigs and combined contig length of the de novo assembly for chosen K-values.
Data
Number of reads mapping against hg19 before and after duplicate removal and percentage of the genome where coverage is at least one.
Data
Results of the recombination analysis using the methods RDP, GENECOV, Chimera, MaxChi, BootScan, SiScan, 3Seq within the RDP v4 software package with all modern full reference genomes (n = 493) and five ancient genomes.
Data
Accession numbers for the reference genomes used in the first alignment step to catch HBV diversity in the sample. Since monkey HBV strains are not classified into genotypes the column is left blank.
Data
Maximum-likelihood tree based on the multiple sequence alignment of the 493 representative and five ancient HBV genomes with 2000 replicates.
Data
Neighbour-Joining tree based on the multiple sequence alignment of the 493 representative modern and five ancient HBV genomes with 10000 replicates.
Data
Final consensus length after retrieving gap information from the multiple sequence alignment with Geneious.
Data
Basic statistics for the mapping against the references shown in table S1. Shown are mean coverage, mean coverage for the covered region, genome length, number of missing bases and covered bases
Article
Full-text available
The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one...
Preprint
Full-text available
The hepatitis B virus (HBV) is one of the most widespread human pathogens known today, yet its origin and evolutionary history are still unclear and controversial. Here, we report the analysis of three ancient HBV genomes recovered from human skeletons found at three different archaeological sites in Germany. We reconstructed two Neolithic and one...
Article
Full-text available
Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on...
Data
Proportion of variants present on derived haplotypes likely due to recombination. Y-axis shows, of all the variable sites (with median pairwise difference of 10 and higher, marked in S3 Fig) present on the derived haplotypes (carrying the rs10166942 derived T allele), which proportion of the alleles are also present in the ancestral haplotypes (car...
Data
Neighbor-Joining tree for the 1KGP populations, based on the genome-wide FST matrix. (PDF)
Data
Recombination landscape across the TRPM8 locus. Recombination map based on average recombination rate in two randomly chosen populations per continental group, to avoid biases due to different numbers of populations per continent (YRI, LWK for Africa; GBR, TSI for Europe; CHB, GIH for Asia). The TRPM8 gene is between the two blue vertical dashed li...
Data
Tissue expression of TRPM8 according to GTEx dataset. Known eQTLs are absent in the region (RegulomeDB [60]), although the restricted expression of the gene may hamper their identification. Because the gene is also expressed in prostate according to GTEx [61], we investigated if rs10166942 affects expression in this tissue type. rs10166942 was not...
Data
Pairwise differences among haplotypes carrying the derived rs10166942 T allele. Distribution of pairwise differences of each haplotype carrying the rs10166942 derived T allele (derived haplotype) with all other derived haplotypes within a population. We show one representative population for each continent: YRI (Africa), CHB (East Asia), GIH (South...
Data
RMSE plots. Information contained within each PLS component for a given parameter for all three models combined for (A) the European model and (B) the Asian model. t0 (time when selection started), sA (selection strength in Africa), sNA (selection strength in non-Africa), fsel Africa (frequency of the allele at selection start in Africa), fsel Non-...
Data
Power results of ABC analysis with selection ceased 3,000 years ago. Power of ABC analysis to correctly assign the model in simulations of European and Asian demography using 10,000 random samplings. TP (True Positive), FP (False Positive), and FN (False Negative). (DOCX)
Data
Protein-coding variants located in TRPM8. Three variants in close proximity to rs10166942 (all with intermediate to low LD) are non-synonymous (rs7593557 S419N r2 = 0.28, rs13004520 R247T r2 = 0.06, rs17868387 Y251C r2 = 0.06), but they all fall in the N-terminal domain of TRPM8 and are unlikely to affect protein function. There are no indels that...
Data
SGDP population overview. Map showing the geographic origin of each population and its rs10166942 T allele count for the two individuals sampled (additional information Supplemental Dataset 1). (PDF)
Data
Latitude and age of each pre-historic European considered. Colour indicates ancestry group: EF for Early Farmers (orange), HG for Hunter-Gatherers (blue), and SP for individuals of Steppe pastoralist ancestry (red). The genotype of the ancient individual is indicated by its symbol (. for missing data; 0 for homozygote ancestral; 1 for heterozygote;...
Data
Linkage disequilibrium across extended TRPM8 locus. Haploview (https://www.broadinstitute.org/haploview/haploview) plots for (A) CHB and (B) FIN across a +-20 kb extended region surroundingTRPM8. (PDF)
Data
ABC analysis with selection halted 3,000 years ago. Posterior probabilities for each model and population. (PDF)
Data
Model stability. Full model stability estimates for each fixed and random effect in each analysis (original estimate obtained from the full data set and the range of estimates derived from omitting individuals and populations (GLMM) or populations (PGLS), one at a time). The small ranges around the original value indicate the overall good stability...
Data
Power results of ABC analysis to differentiate continuous selection and selection ceased 3,000 years ago. Power of ABC analysis to correctly assign the selection model in simulations of European and Asian demography using 10,000 random samplings. TP (True Positive), FP (False Positive), and FN (False Negative). (DOCX)
Data
Migraine prevalence and derived allele frequency. Migraine prevalence per country gathered from Stovner et al. [57]. When multiple samplings per population were available, mean migraine prevalence or mean DAF reported. Pearson correlation between DAF and migraine prevalence: rho = 0.61 (p-value = 0.11). (DOCX)
Data
Selection signatures across the TRPM8 locus. Empirical P-values for FST (blue circles) and XP-EHH (grey diamonds) in the extended TRPM8 region in all populations analysed. The position of TRPM8 is indicated by an orange bar on top, while the strongly differentiated upstream region is between the two vertical blue lines. The red circle marks the FST...
Data
Cloud plots of PLS transformed statistics. Scatter plots of all five PLS components used in the ABC inference for Europe (A & C) and Asia (B & D). (A & B) PLS transformed statistics for the SSV model and their correlation with the three parameters associated with the SSV model: s_time (time when selection started), s_strength NA (selection strength...
Data
Linked diversity. (A) Diversity estimates measured by means of the number of pairwise differences for all haplotypes carrying the derived rs10166942 T allele. (B) Same as in A after removing haplotypes with evidence of recombination (see Materials and methods and S3 and S4 Figs). (DOCX)
Data
Power results of ABC analysis with continuous selection. Power of ABC analysis to correctly assign the model in simulations of European and Asian demography using 10,000 random samplings. TP (True Positive), FP (False Positive), and FN (False Negative). (DOCX)
Data
ABC results of the halted SSV model for each population. Bayes factor (measure of confidence) and the resulting posterior probability (Post. Prob.) for the SSV model in each population, ordered by latitude. t0: time when selection starts; SNA: selection strength in non-African population (ceased 3,000 years ago); fsel: frequency of allele at select...
Data
Overview SGDP data. For each individual used from the SGDP ‘C Panel’ the ID, population, continent, rs10166942 ancestral and derived allele count, latitude, longitude and mean yearly temperature are given. (TXT)
Preprint
Full-text available
Ambient temperature is a critical environmental factor for all living organisms. It was likely an important selective force as modern humans recently colonized temperate and cold Eurasian environments. Nevertheless, as of yet we have limited evidence of local adaptation to ambient temperature in populations from those environments. To shed light on...
Article
Yersinia pestis, the etiologic agent of plague, is a bacterium associated with wild rodents and their fleas. Historically it was responsible for three pandemics: the Plague of Justinian in the 6th century AD, which persisted until the 8th century [ 1 ]; the renowned Black Death of the 14th century [ 2, 3 ], with recurrent outbreaks until the 18th c...
Article
Revelations from a Vindija Neandertal genome Neandertals clearly interbred with the ancestors of non-African modern humans, but many questions remain about our closest ancient relatives. Prüfer et al. present a 30-fold-coverage genome sequence from 50,000- to 65,000-year-old samples from a Neandertal woman found in Vindija, Croatia, and compared th...
Article
While a comparatively young area of research, investigations relying on ancient DNA data have been highly valuable in revealing snapshots of genetic variation in both the recent and the not-so-recent past. Born out of a tradition of single-locus PCR-based approaches that often target individual species, stringent criteria for both data acquisition...
Article
Full-text available
Molecular signatures of Yersinia pestis were recently identified in prehistoric Eurasian individuals, thus suggesting Y. pestis caused some form of disease in humans prior to the first historically documented pandemic. Here, we present six new Y. pestis genomes spanning from the European Late Neolithic to the Bronze Age (LNBA) dating from 4,800 to...
Article
Full-text available
The influence of positive selection sweeps in human evolution is increasingly debated, although our ability to detect them is hampered by inherent uncertainties in the timing of past events. Ancient genomes provide snapshots of allele frequencies in the past and can help address this question. We combine modern and ancient genomic data in a simple...
Data
List of genic alleles in the DAnc European tail. Union of alleles in the tails of all European DAnc (YRI, P2, Ust'-Ishim) distribution (P2: GBR, FIN, TSI, or CEU) including the genomic position (hg19), rs ID (dbSNP b138), and gene overlapping the SNP position. Table published alongside the manuscript as a tsv file.
Data
Supplementary Figures, Supplementary Tables, Supplementary Notes and Supplementary References Supplementary Figures 1-31, Supplementary Tables 1-2, Supplementary Notes 1-2 and Supplementary References
Data
Zip archive containing the shell and R code used for all major analyses. A tarball is also available on our website (https://bioinf.eva.mpg.de/download/PopDiff_aDNA_study/).
Data
DAnc results using present-day modern humans instead of Ust'-Ishim. DAnc analysis was performed for YRI as P1 and the European or East Asian populations as P2, and the ancient Ust'-Ishim genome was replaced with a single high-coverage genome from the B team presented in Meyer et al.11. We used all individuals of Asian or Oceanian ancestry (SS600446...
Article
Full-text available
Balancing selection is an important evolutionary force that maintains genetic and phenotypic diversity in populations. Most studies in humans have focused on long-standing balancing selection, which persists over long periods of time and is generally shared across populations. But balanced polymorphisms can also promote fast adaptation, especially...
Article
Full-text available
Interferon lambda 4 gene (IFNL4) encodes IFN-λ4, a new member of the IFN-λ family with antiviral activity. In humans IFNL4 open reading frame is truncated by a polymorphic frame-shift insertion that eliminates IFN-λ4 and turns IFNL4 into a polymorphic pseudogene. Functional IFN-λ4 has antiviral activity but the elimination of IFN-λ4 through pseudog...
Article
Full-text available
Most human polymorphisms are neutral or slightly deleterious, but some genetic variation is advantageous and maintained in populations by balancing selection. Considered a rarity and overlooked for years, balanced polymorphisms have recently received renewed attention with several lines of evidence showing their relevance in human evolution. From t...

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