Ancient Gaelic history describes the origins of the Irish people as a series of ancient invasions. The two most important migrations in Europe were the Neolithic transition (~3750 BC) and the Bronze Age transition (~2300 BC). The Neolithic period was characterized by the introduction of animal husbandry and cereal crops. Throughout mainland Europe this Neolithic period was accompanied by large population changes, as farmers from southwest Asia replaced much of the population living in Europe. Similarly, the beginning of the Bronze Age was accompanied by population changes as the Yamnaya steppe herders moved across the European continent. Cassidy et al. (2016) recently analyzed genomeic data from four ancient Irish individuals to determine if these same population changes also occurred in the British Isles, or if there were cultural adoption changes instead. The ancient remains of a Neolithic woman from Ballynahatty (dated at 3343-3020 BC) were analyzed by high-throughput sequencing. This determined that she belonged to mitochondrial clade HV0 – a clade with high frequencies in Neolithic samples from Germany and France. Analysis of her nuclear genome confirmed that she likely descended from migrating farmers from the Near East, like other Neolithic populations on the European continent. She was also shown to have some hunter-gatherer ancestry, suggesting mixing of the immigrating Neolithic farmers with the Mesolithic populations of the region. Interestingly, this Irish Neolithic woman shared more similarities with Spanish Neolithic samples compared to samples from Germany. This indicates that the Neolithic farmers may have migrated to Ireland via the southern coastal route, rather than through central Europe. The other three individuals analyzed in this study were three males from the Early Bronze Age (2026-1534 BC). These three individuals belonged to mitochondrial haplogroups U5 and J2b and the Y chromosome haplogroup R1b1a2a1a2c. This Y haplogroup has been strongly linked to the Steppe herders, and shows an east-west frequency gradient in modern populations, with a very high frequency (94%) in the West of Ireland. The genome of the Neolithic woman had the closest affinity to modern southwest Mediterranean populations. A comparison of the Irish Bronze Age genomes to modern populations showed a high affinity to present-day Irish, Scottish and Welsh populations, but a weaker link to modern English populations (likely due to the influence of Anglo-Saxon migrations into England). This indicates a degree of continuity for the “Atlantic Celtic Genome” stretching back over 4000 years to the Early Bronze Age. The DNA obtained from the Neolithic woman and one Bronze Age man allowed for high coverage of the nuclear genomes. The Neolithic woman was heterozygous for the H63D allele of the HFE gene, while the Bronze Age man was heterozygous for the more penetrant C282Y allele. These two hemochromatosis alleles are more common in Irish populations than any other population worldwide, and this study has shown that these disease-associated alleles appeared in the Irish population by the Bronze Age. It has been proposed that they have retained a high frequency due to either a nutritional advantage or resistance to infection (e.g. typhoid fever or tuberculosis). References: Cassidy LM, Martiniano R, Murphy EI, Teasdale MD, Mallory J, Hartwell B, G. Bradleya DG (2016). Neolithic and Bronze Age migration to Ireland and establishment of the insular Atlantic genome. Proc Natl Acad Sci U S A. 113(2): 368–373. Byrnes V (2001). Genetic hemochromatosis, a Celtic disease: Is it now time for population screening? Genet Test. 5(2): 127–130. Lucotte G, Dieterlen F (2003). A European allele map of the C282Y mutation of hemochromatosis: Celtic versus Viking origin of the mutation? Blood Cells Mol Dis. 31(2): 262–267.