Ancient DNA Analysis Reveals High Frequency of European Lactase Persistence Allele (T-13910) in Medieval Central Europe

Ruminant milk and dairy products are important food resources in many European, African, and Middle Eastern societies. These regions are also associated with derived genetic variants for lactase persistence. In mammals, lactase, the enzyme that hydrolyzes the milk sugar lactose, is normally down-regulated after weaning, but at least five human populations around the world have independently evolved mutations regulating the expression of the lactase-phlorizin-hydrolase gene. These mutations result in a dominant lactase persistence phenotype and continued lactase tolerance in adulthood. A single nucleotide polymorphism (SNP) at C/T-13910 is responsible for most lactase persistence in European populations, but when and where the T-13910 polymorphism originated and the evolutionary processes by which it rose to high frequency in Europe have been the subject of strong debate. A history of dairying is presumed to be a prerequisite, but archaeological evidence is lacking. In this study, DNA was extracted from the dentine of 36 individuals excavated at a medieval cemetery in Dalheim, Germany. Eighteen individuals were successfully genotyped for the C/T-13910 SNP by molecular cloning and sequencing, of which 13 (72%) exhibited a European lactase persistence genotype: 44% CT, 28% TT. Previous ancient DNA-based studies found that lactase persistence genotypes fall below detection levels in most regions of Neolithic Europe. Our research shows that by AD 1200, lactase persistence frequency had risen to over 70% in this community in western Central Europe. Given that lactase persistence genotype frequency in present-day Germany and Austria is estimated at 71-80%, our results suggest that genetic lactase persistence likely reached modern levels before the historic population declines associated with the Black Death, thus excluding plague-associated evolutionary forces in the rise of lactase persistence in this region. This new evidence sheds light on the dynamic evolutionary history of the European lactase persistence trait and its global cultural implications

Consensus mitochondrial HVRI data for Dalheim human samples and laboratory analysts.

<p><i>Notes:</i></p>*<p>Polymorphic sites are numbered according to the revised Cambridge Reference Sequence (rCRS).</p><p>Reported data consist of the consensus sequence for a minimum of two successful amplifications. A dot indicates identity to the rCRS sequence, and blank cells indicate HVRI loci for which no PCR amplification was attempted.</p>†<p>Performed DNA extractions.</p>‡<p>Performed DNA amplifications.</p

Reported C/T-13910 genotype frequencies in ancient DNA studies.

<p>Reported C/T-13910 genotype frequencies in ancient DNA studies.</p

Reported C/T-13910 allele frequencies in modern DNA studies of western Central Europe.

<p>Reported C/T-13910 allele frequencies in modern DNA studies of western Central Europe.</p

Results of genetic sex and LP allele genotyping.

*<p>Tooth sample was collected from a mixed burial assemblage containing multiple individuals.</p>†<p>Performed DNA extractions.</p>‡<p>Performed DNA amplifications.</p>a<p>M, male; F, female; I, indeterminate. Osteological sex determination is from <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0086251#pone.0086251-Hofmann1" target="_blank">[39]</a>.</p>b<p>A minimum of two independent DNA extractions were performed for each individual.</p><p>LP genotype was determined from sequence clones obtained from a minimum of two successful amplifications from Extract 1 and a minimum of one successful amplification from Extract 2 and/or Extract 3. The combined sequencing results are reported for each extract, as well as the consensus LP genotype and inferred phenotype.</p>c<p>Consensus genetic sex determined from a minimum of two successful amplifications.</p