The Geographical Distribution of Lactose Tolerance-Associated Alleles 13910*T and 13915*G Is Strongly Linked to Male Founder Events in Eurasia

Abstract

Lactose tolerance (lactase persistence) represents a very progressive human adaptation, the origins of which remain incompletely understood. This study aims to examine the geographical distribution of the two alleles associated with lactose tolerance in Eurasia (13910*T and 13915*G) in relation to the main Y haplogroups and autosomal ancestry components. Data on the frequency of the 13910*T allele were collected from 52 countries across Europe, the Near East, and North Africa. The 13915*G allele was available for 30 countries, but was studied in only 16 Near Eastern and North African countries, as it is absent in Europe. The findings indicate very robust, linear relationships between allele frequencies and the genetic factors examined. The strong correlation between the occurrence of the 13910*T allele and Yamnaya ancestry supports the hypothesis that 13910*T originated from the steppe Yamnaya culture. However, its subsequent dissemination can be attributed to a series of regional male founder events and the spread of specific Y haplogroups, particularly Y haplogroup I1. Conversely, the current occurrence of the 13915*G allele appears to have a less complex origin, associated with the geographically constrained expansion of pastoral populations with Natufian ancestry and Y haplogroup J1 in the Arabian Peninsula. 1 | Introduction Lactose tolerance (lactase persistence) is one of the most fascinating human adaptations. After weaning, young mammals lose the ability to digest the milk sugar lactose because their bodies stop producing the key enzyme lactase in the small intestine. However, some human populations have retained this ability through strong genetic selection, turning it into an extraordinary evolutionary advantage. In fact, the selection for lactose tolerance is one of the fastest processes of genetic selection ever observed in humans (Ségurel and Bon 2017). The production of lactase is governed by the LCT gene on chromosome 2 (2q21.3 region), but mutated SNPs (single-­nucleotide polymorphisms) responsible for lactase persistence in adulthood are located in intron 13 of the neighboring MCM6 gene, which has a regulatory function in relation to LCT (Ségurel and Bon 2017; Cohen et al. 2024) (Figure 1). Currently, several such mutations are known; the most important of them are the Eurasian variants 13910*T (rs4988235) and 13915*G (rs41380347). …