Biology subjects

Bradley, D. G.

Publications and source records attributed to Bradley, D. G..

16 recordsLinked to original sources

bioRxiv2026

Plague-driven selection enriched familial Mediterranean fever mutations in Armenia

The discovery that positive selection due to resistance to malarial infection maintained the prevalence of sickle cell and other disease alleles was a landmark in evolution, genetics and epidemiology. Mutations in the MEFV gene causing familial Mediterranean fever with high frequency in Eastern Mediterranean populations give the only other strong candidates for a similar process. Here we estimate a pathogenic MEFV mutation burden in Armenians with a carrier rate of ~41%: a worldwide maximum. By combining these data with regional ancient MEFV genotypes spanning more than 60 centuries, we establish that the allele frequencies of three mutations M694V, M680I, and V726A underwent recent rapid increases, indicating positive selection with an onset consistent with the first Yersinia pestis plague pandemic, ~541 CE to 767 CE or even earlier in time, echoing functional data implying resistance to this infection as the selective agent. This extends to three the number of MEFV variants for which there is evidence for strong concurrent selection at this locus in the Eastern Mediterranean, making it unlikely that this geographic peak resulted from chance alone. Although bubonic plague was extremely widespread, the restricted geography of this selection points toward the Eastern Mediterranean as a longstanding enzootic centre with continuous recycling of outbreaks.

genomics↗

bioRxiv2026

PIGSTI: a modular, reproducible pipeline for detecting species identity, pathogens, and microbes from animal palaeogenomic data

Ancient genomics has enabled discovery of diverse pathogens across various time periods, host species, and material types. However, existing palaeogenomic pipelines predominantly focus on screening data from human hosts, or do not incorporate microbial screening methodologies. We present PIGSTI (Pathogen anImal Genome Sequence ToolkIt), a bioinformatic pipeline specifically designed for both the initial screening and subsequent detection of pathogens in shotgun sequencing data from ancient animal remains. PIGSTI's integrated Snakemake workflow performs both host detection, genome mapping and pathogen identification, generating outputs suitable for population genetics and phylogenetic analyses. Testing on 952 newly sequenced and publicly available animal palaeogenomic datasets, we identified ~15 ancient zoonotic and animal pathogens with high confidence, including the first documented case of Rickettsia felis and Leptospira borgpetersenii in an ancient animal. Our results demonstrate PIGSTI's utility for screening pathogen diversity in ancient animal hosts and reconstructing historical host-pathogen relationships.

genomics↗

bioRxiv2026

Mediterranean dispersal imposed bottlenecks in Neolithic sheep and goats

The Neolithic period in western Eurasia involved major dispersal events, including the translocation of livestock into Europe. These domestic animal translocations likely featured founder effects, fundamentally reshaping their genetic landscape. One well-known example is the Mediterranean dispersal, hypothesised to involve rapid maritime translocation with small founding herds, yet the genetic consequences for the livestock themselves remain poorly understood. To investigate this, we generated 12 palaeogenomes of sheep and goat from La Draga and Cova de lAvellaner, and coanalyzed these with other Neolithic Mediterranean assemblages, including 4 additional novel genomes. We observe a significantly lower genetic diversity and higher runs of homozygosity (ROH) in Iberian sheep and goat populations compared to other ancient European and southwest Asian populations. We quantify the magnitude of the bottleneck in goats at [~]205 Ne, highlighting the severity of the founder event. We further identify species-specific demographic trajectories: goats experienced a severe and prolonged bottleneck, likely driven by regional isolation within the western Mediterranean, intensive exploitation strategies, and small initial founding herds, while sheep were likely more frequently exchanged across the region. Lastly, identity-by-descent (IBD) indicates connectivity along the Mediterranean coast compatible with a cabotage model. This suggests that seaways facilitated rapid initial dispersal but not sustained livestock transfer from southwest Asia, shaping the genetic foundation of Iberian livestock herds. SignificanceThe Neolithic transition in western Eurasia fundamentally restructured human societies, yet the genetic consequences for translocated livestock remain poorly characterized. Analyzing 16 novel palaeogenomes from Mediterranean Neolithic sheep and goats, we demonstrate that maritime dispersal imposed severe founder effects on early Iberian livestock, reducing effective population sizes to as low as [~]205 in goats. Species-specific demographic trajectories reveal that goats experienced prolonged genetic isolation within the western Mediterranean, while sheep maintained broader regional connectivity. Identity-by-descent analyses support a cabotage model of coastal dispersal, indicating that Mediterranean seaways facilitated rapid initial colonization but not sustained genetic exchange with southwest Asian source populations. These findings reveal that the earliest livestock introductions into Europe were demographically constrained events whose genetic signatures persist in the foundations of Iberian pastoral heritage.

genomics↗

bioRxiv2026

Evolutionary history and genomic vulnerability of the extinct giant deer Megaloceros giganteus

The extinct giant deer (Megaloceros giganteus) was one of the most striking megafaunal species of the Late Quaternary, distinguished by its enormous palmated antlers reaching up to 3.5 m across, the largest known among both living and extinct cervids. Despite its iconic status, little is known about its genomic history prior to extinction [~]8 thousand years ago (kya). We generated the first nuclear palaeogenomes for Megaloceros, represented by nine individuals from Germany ([~]40 kya) and Ireland ([~]11 kya), mapped to a new chromosome-level reference genome of the fallow deer (Dama dama). Phylogenomic analyses placed Megaloceros as sister to Dama (divergence [~]3.5 Ma) and revealed evidence of gene flow with ancestral Cervus lineages. Population analyses identified clear differentiation between German and Irish lineages, with higher genetic diversity in the German individuals. Two genes under strong positive selection, BNIPL and SLC10A7, are associated with apoptosis regulation and skeletal development/bone mineralisation, respectively, and may relate to the species large body and antler size. Demographic reconstructions indicate a long-term decline in effective population size, extremely low heterozygosity, little evidence of extensive runs of homozygosity, and an elevated burden of predicted deleterious alleles. Together, these results suggest that Megaloceros entered the terminal Pleistocene in a genomically fragile state, offering new insight into the biology and evolutionary legacy of one of the largest and most distinctive cervids that ever lived.

evolutionary biology↗

bioRxiv2025

Genetic analysis of 7,000 year old preserved goat leather from Cueva de los Murcielagos (Albunol, Spain).

Advances in ancient DNA research have expanded the range of materials from which genetic information can be recovered, enabling the analysis of atypical materials. These often preserve both host and exogenous DNA, for example due to handling or native microbes, offering a window into past diversity. Here we report one such exceptional material: a well-preserved goat leather specimen from Cueva de los Murcielagos (Albunol, Spain), associated with an Early Neolithic context. Archaeozoological analyses show clear evidence of tanning and anthropogenic modification of the skin, while radiocarbon dating confirms it to be [~]7,250-7,000 years old. We generated genome-wide data from the leather (Murcielagos1) and demonstrated that it derives from a domestic goat of European ancestry. Comparisons with modern goats show highest affinity to the Bermeya breed from northern Spain, demonstrating genetic connectivity in goat herds from the Neolithic to present day Iberia. We additionally recover fragmented DNA from the leather deriving from human and canid sources, the former likely reflecting handling/wearing of the leather and the latter indicating post-depositional disturbance. Murcielagos1 represents one of the oldest nuclear genome data from organic remains outside of high altitude, high latitude regions, and demonstrates the value of ancient DNA analysis in exceptional cases of organic preservation.

genomics↗

bioRxiv2025

Palaeoproteomic and genetic insights into millennial-scale dairy consumption in Armenia

Dairy products are a key component of the diet in Armenia today, yet the origins of milk consumption, its historical development, and genetic adaptations related to milk digestion in the region remain understudied. Here, we investigate the co-evolution of dairying practices and lactase persistence in Armenia through combined palaeoproteomic and genetic analyses spanning from prehistory to the present. Our palaeoproteomic results provide direct evidence for milk consumption in prehistoric Armenia and, in conjunction with existing regional data, indicate that dairying was an established component of the South Caucasus subsistence economy from at least the late fourth millennium BCE. We found evidence of milk consumption from multiple species across archaeological periods, with cattle milk representing the earliest confirmed evidence from the Chalcolithic period. Notably, milk proteins were predominantly recovered from high-altitude sites, suggesting that dairy consumption served as an adaptive strategy for harsh highland environmental conditions. In contrast to the widespread evidence for milk consumption, our genetic findings indicate that the lactase persistence-associated variants never reached high frequencies throughout Armenian prehistory. This pattern suggests that the relatively low frequency of lactase persistence may reflect a predominant cultural adaptation to the fermentation of dairy products, which reduces lactose content and enables dairy use even in genetically lactose-intolerant populations.

evolutionary biology↗

bioRxiv2024

Medieval genomes from eastern Iberia illuminate the role of Morisco mass deportations in dismantling a long-standing genetic bridge with North Africa

BackgroundThe Islamic influence on the Iberian Peninsula left an enduring legacy culturally and linguistically, however the demographic impact is less well understood. This study aims to explore the dynamics of gene flow and population structure in eastern Iberia from the early to late Medieval period through ancient DNA. ResultsOur comprehensive genomic analysis uncovered gene flow from various Mediterranean regions into Iberia before the Islamic period, supporting a pre-existing pan-Mediterranean homogenization phenomenon during the Roman Empire. North African ancestry is present but sporadic in late antiquity genomes but becomes consolidated during the Islamic period. We uncovered one of the earliest dated Islamic burials in Spain, which showed high levels of inbreeding. For the first time we also prove the persistence of North African ancestry in a Christian cemetery until the 17th century, in addition to evidence of slave traffick from the Maghreb. ConclusionsThis study reveals the complex interaction between political events and cultural shifts that influenced the population of eastern Iberia. It highlights the existence of a slave trade and underscores the lasting impact of historical events, such as the Expulsion of the Moriscos in 1609 CE, on the regions genetic and cultural landscape through mass population displacement and replacement.

evolutionary biology↗

bioRxiv2023

Ancient genomes illuminate Eastern Arabian population history and adaptation against malaria

The harsh climate of Arabia has posed challenges in generating ancient DNA from the region, hindering the direct examination of ancient genomes for understanding the demographic processes that shaped Arabian populations. In this study, we report whole genome sequence data obtained from four Tylos-period individuals from Bahrain. Their genetic ancestry can be modelled as a mixture of sources from ancient Anatolia, Levant and Iran/Caucasus, with variation between individuals suggesting population heterogeneity in Bahrain before the onset of Islam. We identify the G6PD Mediterranean mutation associated with malaria-resistance in three out of four ancient Bahraini samples and estimate that it rose in frequency in Eastern Arabia from 5-6 kya onwards, around the time agriculture appeared in the region. Our study provides the first characterisation of the genetic composition of ancient Arabians, shedding light on the population history of Bahrain and demonstrating the feasibility of aDNA studies in the region.

genomics↗

bioRxiv2022

A novel lineage of the Capra genus discovered in the Taurus Mountains of Turkey using ancient genomics.

AO_SCPLOWBSTRACTC_SCPLOWDirekli Cave, located in the Taurus Mountains of southern Turkey, was occupied by Late Epipaleolithic hunters-gatherers for the seasonal hunting and processing of game including large numbers of wild goats. We report genomic data from new and published Capra specimens from Direkli Cave and, supplemented with historic genomes from multiple Capra species, find a novel lineage best represented by a [~]14,000 year old 2.59X genome sequenced from specimen Direkli4. This newly discovered Capra lineage is a sister clade to the Caucasian tur species (Capra cylindricornis and Capra caucasica), both now limited to the Caucasus region. We identify genomic regions introgressed in domestic goats with high affinity to Direkli4, and find that West Eurasian domestic goats in the past, but not those today, appear enriched for Direkli4-specific alleles at a genome-wide level. This forgotten "Taurasian tur" likely survived Late Pleistocene climatic change in a Taurus Mountain refugia and its genomic fate is unknown.

genomics↗

bioRxiv2022

Millennium-Old Pathogenic Mendelian Mutation Discovery for MultipleOsteochondromas from a Gaelic Medieval Graveyard.

Only a limited number of genetic diseases are diagnosable in archaeological individuals and none have had causal mutations identified in genome-wide screens. Two individuals from the Gaelic Irish Medieval burial ground of Ballyhanna, Co. Donegal, showed evidence of bone tumors consistent with the autosomal dominant condition multiple osteochondromas. Genome sequencing of the earlier individual uncovered a missense mutation in the second exon of EXT1, a specific lesion that has been identified in several modern patients. The later individual lacked this but displayed a novel frameshift mutation leading to a premature stop codon and loss of function in the same gene. These molecular confirmations of a paleopathological diagnosis within a single rural ancient context are surprisingly disjunct, given the observation of clusters of this disease in modern isolated populations and a de novo mutation rate of only 10%.

genomics↗

bioRxiv2021

Genome-wide local ancestry and direct evidence for mitonuclear co-adaptation in African hybrid cattle populations (Bos taurus/indicus)

The phenotypic diversity of African cattle reflects adaptation to a wide range of agroecological conditions, human-mediated selection preferences, and complex patterns of admixture between the humpless Bos taurus (taurine) and humped Bos indicus (zebu) subspecies, which diverged 150-500 thousand years ago. Despite extensive admixture, all African cattle possess taurine mitochondrial haplotypes, even populations with significant zebu biparental and male uniparental nuclear ancestry. This has been interpreted as the result of a human-mediated dispersal ultimately stemming from zebu bulls imported from South Asia during the last three millennia. Here we assess whether ancestry at mitochondrially-targeted nuclear genes in African admixed cattle is impacted by mitonuclear functional interactions. Using high-density SNP data, we find evidence for mitonuclear coevolution across hybrid African cattle populations with a significant increase of taurine ancestry at mitochondrially-targeted nuclear genes. Our results, therefore, support the hypothesis of incompatibility between the taurine mitochondrial genome and the zebu nuclear genome. GRAPHICAL SUMMARY O_FIG O_LINKSMALLFIG WIDTH=170 HEIGHT=200 SRC="FIGDIR/small/457829v2_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@1031fb0org.highwire.dtl.DTLVardef@1575faorg.highwire.dtl.DTLVardef@f4795corg.highwire.dtl.DTLVardef@4ba74e_HPS_FORMAT_FIGEXP M_FIG C_FIG Highlights* Using high-density genome-wide SNP data, we present evidence for mitonuclear coevolution in hybrid African cattle. * We observe a significant increase of taurine ancestry across multiple hybrid populations at mitochondrially-targeted nuclear genes. * Our results provide support for the hypothesis of mitonuclear incompatibility between the zebu nuclear genome and the taurine mitochondrial genome.

evolutionary biology↗

bioRxiv2021

Climate and mountains shaped human ancestral genetic lineages

Extensive sequencing of modern and ancient human genomes has revealed that contemporary populations can be explained as the result of recent mixing of a few distinct ancestral genetic lineages1. But the small number of aDNA samples that predate the Last Glacial Maximum means that the origins of these lineages are not well understood. Here, we circumvent the limited sampling by modelling explicitly the effect of climatic changes and terrain on population demography and migrations through time and space, and show that these factors are sufficient to explain the divergence among ancestral lineages. Our reconstructions show that the sharp separation between African and Eurasian lineages is a consequence of only a few limited periods of connectivity through the arid Arabian peninsula, which acted as the gate out of the Arican continent. The subsequent spread across Eurasia was then mostly shaped by mountain ranges, and to a lesser extent deserts, leading to the split of European and Asians, and the further diversification of these two groups. A high tolerance to cold climates allowed the persistence at high latitudes even during the Last Glacial Maximum, maintaining a pocket in Beringia that led to the later, rapid colonisation of the Americas. The advent of food production was associated with an increase in movement2, but mountains and climate have been shown to still play a major role even in this latter period3,4, affecting the mixing of the ancestral lineages that we have shown to be shaped by those two factors in the first place.

genomics↗

bioRxiv2020

Phylogeny and distribution of Y-chromosomal haplotypes in domestic, ancient and wild goats

The male-specific part of the Y-chromosome is in mammalian and many other species the longest haplotype that is inherited without recombination. By its paternal transmission it has a small effective population size in species with dominant males. In several species, Y-chromosomal haplotypes are sensitive markers of population history and introgression. Previous studies have identified in domestic goats four major Y-chromosomal haplotypes Y1A, Y1B, Y2A and Y2B with a marked geographic differentiation and several regional variants. In this study we used published whole-genome sequences of 70 male goats from 16 modern breeds, 11 ancient-DNA samples and 29 samples from seven wild goat species. We identified single-copy male-specific SNPs in four scaffolds, containing SRY, ZFY, DBY with SSX3Y and UTY, and USP9Y with UMN2001, respectively. Phylogenetic analyses indicated haplogroups corresponding to the haplotypes Y1B, Y2A and Y2B, respectively, but Y1A was split into Y1AA and Y1AB. All haplogroups were detected in ancient DNA samples from southeast Europe and, with the exception of Y1AB, in the bezoar goat, which is the wild ancestor of the domestic goats. Combining these data with those of previous studies and with genotypes obtained by Sanger sequencing or the KASP assay yielded haplogroup distributions for 132 domestic breeds or populations. The phylogeographic differentiation indicated paternal population bottlenecks on all three continents. This possibly occurred during the Neolithic introductions of domestic goats to those continents with a particularly strong influence in Europe along the Danubian route. This study illustrates the power of the Y-chromosomal haplotype for the reconstructing the history of mammalian species with a wide geographic range.

genetics↗

bioRxiv2017

Insular Celtic population structure and genomic footprints of migration

Previous studies of the genetic landscape of Ireland have suggested homogeneity, with population substructure undetectable using single-marker methods. Here we have harnessed the haplotype-based method fineSTRUCTURE in an Irish genome-wide SNP dataset, identifying 23 discrete genetic clusters which segregate with geographical provenance. Cluster diversity is pronounced in the west of Ireland but reduced in the east where older structure has been eroded by historical migrations. Accordingly, when populations from the neighbouring island of Britain are included, a west-east cline of Celtic-British ancestry is revealed along with a particularly striking correlation between haplotypes and geography across both islands. A strong relationship is revealed between subsets of Northern Irish and Scottish populations, where discordant genetic and geographic affinities reflect major migrations in recent centuries. Additionally, Irish genetic proximity of all Scottish samples likely reflects older strata of communication across the narrowest inter-island crossing. Using GLOBETROTTER we detected Irish admixture signals from Britain and Europe and estimated dates for events consistent with the historical migrations of the Norse-Vikings, the Anglo-Normans and the British Plantations. The influence of the former is greater than previously estimated from Y chromosome haplotypes. In all, we paint a new picture of the genetic landscape of Ireland, revealing structure which should be considered in the design of studies examining rare genetic variation and its association with traits.\n\nAuthor summaryA recent genetic study of the UK (People of the British Isles; PoBI) expanded our understanding of population history of the islands, using newly-developed, powerful techniques that harness the rich information embedded in chunks of genetic code called haplotypes. These methods revealed subtle regional diversity across the UK, and, using genetic data alone, timed key migration events into southeast England and Orkney. We have extended these methods to Ireland, identifying regional differences in genetics across the island that adhere to geography at a resolution not previously reported. Our study reveals relative western diversity and eastern homogeneity in Ireland owing to a history of settlement concentrated on the east coast and longstanding Celtic diversity in the west. We show that Irish Celtic diversity enriches the findings of PoBI; haplotypes mirror geography across Britain and Ireland, with relic Celtic populations contributing greatly to haplotypic diversity. Finally, we used genetic information to date migrations into Ireland from Europe and Britain consistent with historical records of Viking and Norman invasions, demonstrating the signatures of these migrations the on modern Irish genome. Our findings demonstrate that genetic structure exists in even small isolated populations, which has important implications for population-based genetic association studies.

genetics↗

bioRxiv2017

The York Gospels: a one thousand year biological palimpsest

Medieval manuscripts, carefully curated and conserved, represent not only an irreplaceable documentary record but also a remarkable reservoir of biological information. Palaeographic and codicological investigation can often locate and date these documents with remarkable precision. The York Gospels (York Minster Ms. Add. 1) is one such codex, one of only a small collection of pre-conquest Gospel books to have survived the Reformation. By extending the non-invasive triboelectric (eraser-based) sampling technique eZooMS, to include the analysis of DNA we report a cost effective and simple-to-use biomolecular sampling technique. We apply this combined methodology to document for the first time a rich palimpsest of biological information contained within the York Gospels, which has accumulated over the 1,000 year lifespan of this cherished object that remains an active participant in the life of York Minster. This biological data provides insights into the decisions made in the selection of materials, the construction of the codex and the use history of the object.

genomics↗

bioRxiv2017

The Population Genomics Of Archaeological Transition In West Iberia

We analyse new genomic data (0.05-2.95x) from 14 ancient individuals from Portugal distributed from the Middle Neolithic (4200-3500 BC) to the Middle Bronze Age (1740-1430 BC) and impute genomewide diploid genotypes in these together with published ancient Eurasians. While discontinuity is evident in the transition to agriculture across the region, sensitive haplotype-based analyses suggest a significant degree of local hunter-gatherer contribution to later Iberian Neolithic populations. A more subtle genetic influx is also apparent in the Bronze Age, detectable from analyses including haplotype sharing with both ancient and modern genomes, D-statistics and Y-chromosome lineages. However, the limited nature of this introgression contrasts with the major Steppe migration turnovers within third Millennium northern Europe and echoes the survival of non-Indo-European language in Iberia. Changes in genomic estimates of individual height across Europe are also associated with these major cultural transitions, and ancestral components continue to correlate with modern differences in stature.\n\nAuthor SummaryRecent ancient DNA work has demonstrated the significant genetic impact of mass migrations from the Steppe into Central and Northern Europe during the transition from the Neolithic to the Bronze Age. In Iberia, archaeological change at the level of material culture and funerary rituals has been reported during this period, however, the genetic impact associated with this cultural transformation has not yet been estimated. In order to investigate this, we sequence Neolithic and Bronze Age samples from Portugal, which we compare to other ancient and present-day individuals. Genome-wide imputation of a large dataset of ancient samples enabled sensitive methods for detecting population structure and selection in ancient samples. We revealed subtle genetic differentiation between the Portuguese Neolithic and Bronze Age samples suggesting a markedly reduced influx in Iberia compared to other European regions. Furthermore, we predict individual height in ancients, suggesting that stature was reduced in the Neolithic and affected by subsequent admixtures. Lastly, we examine signatures of strong selection in important traits and the timing of their origins.

genomics↗