A sequencing study comparing ancient and contemporary genomes reveals that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, ancient north Eurasians (related to Upper Palaeolithic Siberians) and early European farmers of mainly Near Eastern origin. By sequencing and comparing the genomes of nine ancient Europeans that bridge the transition to agriculture in Europe between 8,000 and 7,000 years ago, David Reich and colleagues show that most present-day Europeans derive from at least three highly differentiated populations — west European hunter-gatherers, ancient north Eurasians (related to Upper Palaeolithic Siberians) and early European farmers of mainly Near Eastern origin. They further propose that early European farmers had about 44% ancestry from a 'basal Eurasian' population that split before the diversification of other non-African lineages. These results raise interesting new questions, for instance that of where and when the Near Eastern farmers mixed with European hunter-gatherers to produce the early European farmers. We sequenced the genomes of a ∼7,000-year-old farmer from Germany and eight ∼8,000-year-old hunter-gatherers from Luxembourg and Sweden. We analysed these and other ancient genomes1,2,3,4 with 2,345 contemporary humans to show that most present-day Europeans derive from at least three highly differentiated populations: west European hunter-gatherers, who contributed ancestry to all Europeans but not to Near Easterners; ancient north Eurasians related to Upper Palaeolithic Siberians3, who contributed to both Europeans and Near Easterners; and early European farmers, who were mainly of Near Eastern origin but also harboured west European hunter-gatherer related ancestry. We model these populations’ deep relationships and show that early European farmers had ∼44% ancestry from a ‘basal Eurasian’ population that split before the diversification of other non-African lineages.

Hyperphenylalaninemia due to a deficiency of hepatic phenylalanine hydroxylase (PAH) is the most common inborn error of amino acid metabolism. Clinically, the disorder is highly heterogeneous, spanning from nonphenylketonuria hyperphenylalaninemia to classical phenylketonuria. Only little is known about the molecular defects underlying hyperphenylalaninemia in Southern Europe. In this study, we conducted a systematic analysis of 53 patients from the Sicllian population. Each patient included in the study had persistently elevated blood levels of phenylalanine and met the differential criteria for PAH deficiency. Genomic DNA was analysed by scanning all PAH-coding exons for mutations by PCR in combination with denaturing gradient gel electrophoresis (DGGE). 52 patients were completely genotyped. A spectrum of 40 different mutations was established including 17 novel PAH mutations. Our results explain the clinical heterogeneity of hyperphenylalaninemia in Southern Europe, and form the basis for the establishment of phenotype-genotype correlations in Sicily and surrounding countries.