Low Prevalence of Lactase Persistence in Bronze Age Europe Indicates Ongoing Strong Selection over the Last 3,000 Years

Joachim Bürger ,Ruth Bollongino,Ute Brinker,Amelie Scheu,Krishna R Veeramah,Jens Blöcher,Daniel Wegmann,Aleksandra Žegarac,Zoé Pochon,Jörg Orschiedt,Zuzana Hofmanová,Christoph Leuenberger,Gundula Lidke,Thomas Terberger,Mark G Thomas,Yoan Diekmann,Sofija Stefanović,Carlos S Reyna-Blanco,Anna Schulz,Elke Kaiser,Detlef Jantzen,Thomas S Bertino,Vivian Link,Laura Winkelbach,Christian Sell,Vanessa C Bieker

doi:10.1016/j.cub.2020.08.033

Abstract

Lactase persistence (LP), the continued expression of lactase into adulthood, is the most strongly selected single gene trait over the last 10,000 years in multiple human populations. It has been posited that the primary allele causing LP among Eurasians, rs4988235-A [1], only rose to appreciable frequencies during the Bronze and Iron Ages [2, 3], long after humans started consuming milk from domesticated animals. This rapid rise has been attributed to an influx of people from the Pontic-Caspian steppe that began around 5,000 years ago [4, 5]. We investigate the spatiotemporal spread of LP through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany (∼3,200 before present, BP), the oldest large-scale conflict site north of the Alps. Genetic data indicate that these individuals represent a single unstructured Central/Northern European population. We complemented these data with genotypes of 18 individuals from the Bronze Age site Mokrin in Serbia (∼4,100 to ∼3,700 BP) and 37 individuals from Eastern Europe and the Pontic-Caspian Steppe region, predating both Bronze Age sites (∼5,980 to ∼3,980 BP). We infer low LP in all three regions, i.e., in northern Germany and South-eastern and Eastern Europe, suggesting that the surge of rs4988235 in Central and Northern Europe was unlikely caused by Steppe expansions. We estimate a selection coefficient of 0.06 and conclude that the selection was ongoing in various parts of Europe over the last 3,000 years.

Highlights

These frequency estimates indicate that, the rs4988235-A allele had reached frequencies that make it detectable in small-sample-size ancient DNA studies by the beginning of the Bronze Age in various parts of Europe, it had not reached the frequencies observed in population samples dating from the Iron Age or later
We investigate the spatiotemporal spread of Lactase persistence (LP) through an analysis of 14 warriors from the Tollense Bronze Age battlefield in northern Germany ($3,200 before present, BP), the oldest large-scale conflict site north of the Alps
The Majority of the Tollense Samples Are Male and Unrelated We enriched DNA from 21 samples from the Tollense battlefield for 5 MB of putatively neutral regions and 487 phenotypically informative loci associated with metabolic syndrome, adult lactase persistence (LP), non-infectious and inflammatory diseases, and eye, skin, and hair pigmentation [6]

Summary

Introduction

These frequency estimates indicate that, the rs4988235-A allele had reached frequencies that make it detectable in small-sample-size ancient DNA studies by the beginning of the Bronze Age in various parts of Europe, it had not reached the frequencies observed in population samples dating from the Iron Age or later.

Results

Conclusion