Significance Modern Europe has been shaped by two episodes in prehistory, the advent of agriculture and later metallurgy. These innovations brought not only massive cultural change but also, in certain parts of the continent, a change in genetic structure. The manner in which these transitions affected the islands of Ireland and Britain on the northwestern edge of the continent remains the subject of debate. The first ancient whole genomes from Ireland, including two at high coverage, demonstrate that large-scale genetic shifts accompanied both transitions. We also observe a strong signal of continuity between modern day Irish populations and the Bronze Age individuals, one of whom is a carrier for the C282Y hemochromatosis mutation, which has its highest frequencies in Ireland today.

Abstract The Neolithic and Bronze Age transitions were profound cultural shifts catalyzed in parts of Europe by migrations, first of early farmers from the Near East and then Bronze Age herders from the Pontic Steppe. However, a decades-long, unresolved controversy is whether population change or cultural adoption occurred at the Atlantic edge, within the British Isles. We address this issue by using the first whole genome data from prehistoric Irish individuals. A Neolithic woman (3343–3020 cal BC) from a megalithic burial (10.3× coverage) possessed a genome of predominantly Near Eastern origin. She had some hunter–gatherer ancestry but belonged to a population of large effective size, suggesting a substantial influx of early farmers to the island. Three Bronze Age individuals from Rathlin Island (2026–1534 cal BC), including one high coverage (10.5×) genome, showed substantial Steppe genetic heritage indicating that the European population upheavals of the third millennium manifested all of the way from southern Siberia to the western ocean. This turnover invites the possibility of accompanying introduction of Indo-European, perhaps early Celtic, language. Irish Bronze Age haplotypic similarity is strongest within modern Irish, Scottish, and Welsh populations, and several important genetic variants that today show maximal or very high frequencies in Ireland appear at this horizon. These include those coding for lactase persistence, blue eye color, Y chromosome R1b haplotypes, and the hemochromatosis C282Y allele; to our knowledge, the first detection of a known Mendelian disease variant in prehistory. These findings together suggest the establishment of central attributes of the Irish genome 4,000 y ago.

The oldest Gaelic literature describes the origins of the Irish people as a series of ancient invasions, and the archaeological record in Ireland, as elsewhere in Europe, exhibits several horizons where major cultural shifts are apparent (1). The two most transformative are the arrival of agriculture (∼3750 BC) followed by the onset of metallurgy (∼2300 BC). The Neolithic package characterized by animal husbandry, cereal crops, ceramics, and timber houses reached the shores of Ireland some 5,000 years after its beginnings in the Near East. The second great wave of change starts with the appearance of copper mines, associated with Bell Beaker pottery, which are quickly followed by Bronze tool-making, weaponry, and gold-working, with distinct Food Vessel pottery succeeding from the earlier beakers (2). This period coincides with the end of the large passage graves of Neolithic Ireland in favor of single burials and smaller wedge tombs.

Twentieth-century archaeology was dominated by two non-mutually-exclusive paradigms for how such large scale social change occurs (3). The first, demic diffusion, linked archaeological change with the displacement and disruption of local populations by inward migrations. However, from the 1960s onwards, this assertion was challenged by a paradigm of cultural diffusion whereby social change happened largely through indigenous processes.

High-throughput sequencing has opened the possibility for genome-wide comparisons of genetic variation in ancient populations, which may be informatively set in the context of extensive modern data (4⇓⇓⇓⇓⇓–10). In Europe, these clearly show population replacement by migrating farmers from southwest Asia at the onset of the Neolithic with some retrenchment of the earlier Mesolithic genome at later stages (5⇓⇓⇓–9, 11, 12). Three longitudinal genome studies have also shown later genome-wide shifts around the beginnings of the Bronze Age in central Europe with substantial introgression originating with the Yamnaya steppe herders (7, 9, 10). However, replacement coupled to archaeological horizons is unlikely to be a universal phenomenon, and whether the islands of Britain and Ireland, residing at the temporal and geographical edges of both the Neolithic and steppe migrations, were subject to successive substantial population influxes remains an open and debated question. For example, a recent survey of archaeological opinion on the origins of agriculture in Ireland showed an even split between adoption and colonization as explanatory processes (13). Recent archaeological literature is also divided on the origins of the insular Bronze Age, with most opinion favoring incursion of only small numbers of technical specialists (1, 2, 14, 15).

To address this controversy, we present here the first, to our knowledge, genome-wide data from four ancient Irish individuals, a Neolithic woman (3343–3020 cal BC) from Ballynahatty, Co. Down, found in the context of an early megalithic passage-like grave, and three Early Bronze Age men from a cist burial in Rathlin Island, Co. Antrim (2026–1534 cal BC) with associated Food Vessel pottery (16) (SI Appendix, Section S1).

Discussion The advent of farming in Ireland lies at the temporal and geographical terminus of several thousand years of transition across Europe and seems to occur rapidly ∼ 3750 BC (47). The nature of this transition remains a long-standing archaeological controversy between proposals of migration by incoming farmers versus those of adoption of agriculture by indigenous Mesolithic populations (48⇓⇓–51). The Irish MN female farmer (3343–3020 cal. BC) from a Megalithic tomb in Ballynahatty near Belfast affords, to our knowledge, a first direct genetic view of the transition at Europe’s western edge. She displays predominant ancestry from early farmers that ultimately originated in migrating agriculturists from the Near East. This derivation is attested by her PCA and ADMIXTURE profile, her correlated allele frequencies with other Neolithic genomes, reflected in D statistics, and by her haplotypic affinity with modern southern Mediterranean populations such as Sardinians. Her early European farmer coefficient is estimated at ∼60%; an ancestry which is difficult to reconcile with extensive indigenous adoption of agriculture in Ireland only several hundred years earlier. She shares higher levels of genetic drift with Early and MN samples from Spain rather than those from Germany, supporting a link between the early farming cultures of Atlantic Europe and arguing for the possible passage of farming to Ireland via a southern coastal route rather than via the migrations through central Europe (2). A high affinity to Scandinavian farmer, Gok2 is more difficult to interpret as it is associated with the TRB (Funnelbeaker) culture whose origins are generally derived from Central European farming cultures but perhaps it is noteworthy that this later sample is also recovered from a Megalithic context. From examination of the fraction of her genome, which is under ROH, she seems similar to other ancient Neolithics, suggesting that she belonged to a large outbreeding population. This analysis argues against a marked population bottleneck in her ancestry, such as might have occurred had she been descended from a small pioneering group of migrating farmers. Either a restricted colonization does not reflect the nature of the first Irish farmers or her ancestry was augmented by substantial additional Neolithic communication from elsewhere in intervening centuries. However, like other MN genomes, Ballynahatty shows some elevation of hunter–gatherer ancestry relative to earlier Neolithic samples, suggesting admixture with surviving Mesolithic populations somewhere within the temporal and spatial trajectory between the Neolithic heartland and north east Ireland ∼3300 BC (5, 9). Further sampling will be needed to determine the local or continental origins of these hunter–gatherer ancestral components but it is interesting that she shows slightly higher affinity to a Luxembourger Mesolithic genome, than to Hungarian and Spanish equivalents. There are several lines of evidence for discontinuity between the MN and Early Bronze Age within our genome samples from northeast Ireland. First, they occupy different regions in the PCA plot; second, there is a signal from the ADMIXTURE analysis of a Caucasus ancestral component within the Rathlin genomes, which is absent in Ballynahatty and other western MN genomes. Third, D statistics also show highly significant evidence for this eastern introgression. Finally, each Bronze Age sample (all male) exhibits the Bronze Age-associated Y chromosome lineage R1b-M269, the appearance of which has been strongly linked with Steppe incursion into Central Europe (9). Thus, it is clear that the great wave of genomic change which swept from above the Black Sea into Europe around 3000 BC washed all of the way to the northeast shore of its most westerly island. At present, the Beaker culture is the most probable archaeological vector of this Steppe ancestry into Ireland from the continent, although further sampling from Beaker burials across western Europe will be necessary to confirm this. The extent of this change, which we estimate at roughly a third of Irish Bronze Age ancestry, opens the possibility of accompanying language change, perhaps the first introduction of Indo-European language ancestral to Irish. This assertion gains some support by the relative lack of affinity of non-Indo-European speakers, Basques, to the ancient Bronze Age genomes (Fig. 3). The high coverage of both Ballynahatty and Rathlin1 allows a sensitive test of haplotype donation to modern populations, with interesting and contrasting results. Whereas Ballynahatty shows closest affinity with the southwest Mediterranean, Rathlin1 has highest sharing with the geographically closest modern populations, a trend not seen with the other high coverage ancient genome samples. This affinity with Irish, Scottish, and Welsh (a weaker signal from modern English populations is undoubtedly due to the effects of Anglo-Saxon migrations; ref. 36) suggests a degree of continuity stretching over 4,000 y at the insular Celtic edge of Europe. Ireland shows the global maxima for frequencies of the R1b1a2a1a2c (M529) Y chromosome haplotype, lactase persistence, and the C282Y hemochromatosis allele. Our data show that these genotypes had arrived by the time of the Irish Bronze Age. Hemochromatosis, known as the “Celtic” disease (44), is a variably penetrant recessive disorder, potentially fatal, due to excessive retention of dietary iron. It has been suggested that the high frequencies of both C282Y and H63D are due to heterozygote advantage related to nutritional advantage in Neolithic iron-poor diets (52), mitigation of celiac disease (53), and increased resistance to parasitic infection (54). To our knowledge, our data provide the first evidence for known Mendelian disease alleles in ancient genomes and mark the associations of both hemochromatosis alleles with the island of Ireland as ancient.

Acknowledgments We thank Hellenthal et al. (37) for sharing the genotype data in PLINK format and David McConnell for a critical reading of the manuscript. L.M.C. is funded by the Irish Research Council Government of Ireland Scholarship Scheme (GOIPG/2013/1219). R.M. was financed by the Bridging the European and Anatolian Neolithic project of the Marie Curie Innovative Training Networks (Grant 289966). M.D.T. was supported by European Research Council (ERC) Investigator Grant 295729-CodeX. We acknowledge Science Foundation Ireland (SFI) ERC Support Award 12/ERC/B2227, Valeria Mattiangeli, and TrinSeq for MiSeq support. We acknowledge the DJEI/DES/SFI/HEA Irish Centre for High-End Computing for the provision of computational facilities and support.

Footnotes Author contributions: D.G.B. designed research; L.M.C. and R.M. performed research; E.M.M. contributed new reagents/analytic tools; L.M.C., R.M., M.D.T., and D.G.B. analyzed data; and L.M.C., R.M., E.M.M., M.D.T., J.M., B.H., and D.G.B. wrote the paper.

The authors declare no conflict of interest.

This article is a PNAS Direct Submission.

Data deposition: The sequences reported in this paper have been deposited in the European Nucleotide Archive (project accession no. PRJEB11995).

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