Lactase persistence in Tunisia as a result of admixture with other Mediterranean populations

Abstract

Background: The ability to digest lactose after weaning, namely, lactase persistence (LP), is encoded by polymorphisms in the MCM6 gene and varies widely in frequency among different human populations. Although, evolution of LP-related genetic variants was investigated in many groups of Sub-Saharan African, Middle Eastern, and European ancestry, only few studies have focused on populations from North Africa and no data are especially available from the Tunisian one. For this reason, there is an urgent need to investigate the frequency patterns at these loci in Tunisia since this adaptive trait is implicated in health.

Methods: Forty SNPs covering the LCT/MCM6 genes and including the two functional variants - 13,910 C > T and - 22,018 G > A were genotyped in 117 Tunisian individuals using the Sequenom Mass Array technology. The observed nucleotide and haplotype patterns of variation were then compared with those of several African, European, and Mediterranean human groups for which comparable data were publicly available. Admixture analysis on a 5 Mb genomic region surrounding the LCT/MCM6 loci was also performed by extracting genotypes from a previously generated genome-wide dataset in order to deepen the reconstruction of the evolutionary history of these loci.

Results: We found that lactase non-persistence (LNP)-related alleles and haplotypes were predominantly present in the examined population. A clear differentiation between Tunisian, African, and North European/North Italian samples was found, while the Tunisian population showed more genetic affinity to Central and South Italian groups.

Conclusions: Our study provided a first report of LP-associated alleles and haplotypes in the Tunisian population. We highlighted a gradient followed by LP diffusion from Europe to North Africa. Based on the rich historic background of Tunisia, we suggest that this adaptive trait was introduced in that geographic region by a relatively recent gene flow.

Keywords: Admixture; LCT; Lactase persistence; MCM6; Natural selection; North Africa; Tunisia.

Fig. 1

MDS of Fst estimates based on the LP region for several populations. Non-metric multidimensional scaling analysis of LCT/MCM6 based on Fst distance showing the relationships among the studied populations. ESN Esan in Nigeria, GWD Gambian in Western Division, The Gambia, LWK Luhya in Webuye, Kenya, MSL Mende in Sierra Leone, YRI Yoruba in Ibadan, Nigeria, TSI Tuscany in Italy, CESI Central-Eastern Southern Italy, NEI North-Eastern Italy, NCWI North Central Western Italy, SARD Sardinia, IBS Iberian populations in Spain, FIN Finnish in Finland, GBR British in England and Scotland, CEU Utah residents (CEPH) with Northern and Western European ancestry, TN Tunisian population

Fig. 2

Ancestry proportions at K = 2 to K = 4 estimated by means of ADMIXTURE clustering analysis performed on the extended LP-related region. Population structure of worldwide human populations is shown for 1677 individuals from 33 different groups globally distributed (from left to right: 633 Sub-Saharan Africans, 225 North Africans, 399 Europeans, 77 Mexicans, 255 East Asians, 88 Indians)

Fig. 3

Median joining network of the inferred haplotypes. Haplotypes proportions were displayed with different colors according to the different examined populations. Adaptive haplotype was indicated by arrow