Whole-exome analysis in Tunisian Imazighen and Arabs shows the impact of demography in functional variation

Marcel Lucas-Sánchez,David Comas,Neus Font-Porterias,Francesc Calafell,Karima Fadhlaoui-Zid

doi:10.1038/s41598-021-00576-0

Abstract

Human populations are genetically affected by their demographic history, which shapes the distribution of their functional genomic variation. However, the genetic impact of recent demography is debated. This issue has been studied in different populations, but never in North Africans, despite their relevant cultural and demographic diversity. In this study we address the question by analyzing new whole-exome sequences from two culturally different Tunisian populations, an isolated Amazigh population and a close non-isolated Arab-speaking population, focusing on the distribution of functional variation. Both populations present clear differences in their variant frequency distribution, in general and for putatively damaging variation. This suggests a relevant effect in the Amazigh population of genetic isolation, drift, and inbreeding, pointing to relaxed purifying selection. We also discover the enrichment in Imazighen of variation associated to specific diseases or phenotypic traits, but the scarce genetic and biomedical data in the region limits further interpretation. Our results show the genomic impact of recent demography and reveal a clear genetic differentiation probably related to culture. These findings highlight the importance of considering cultural and demographic heterogeneity within North Africa when defining population groups, and the need for more data to improve knowledge on the region’s health and disease landscape.

Highlights

But others escaped this influence, receding to remote and isolated villages, where they maintained their original culture, language (Tamazight), and Amazigh identity[20,23,24,25,26]
Other studies showed that Europeans and sub-Saharan Africans carry the same amount of derived alleles, despite the severe out-of-Africa bottleneck experienced by Europeans, concluding that genetic load is not affected by recent size c hanges[39,40]
S1 and S2 online) shows Tunisian nonImazighen to have a mixed pattern with a main North African-related component and some traces related to our sub-Saharan, Middle Eastern, and European proxies, while Tunisian Imazighen show a more homogeneous ancestry pattern similar to that shown by Mozabites, an Algerian Amazigh group

Summary

Introduction

But others escaped this influence, receding to remote and isolated villages, where they maintained their original culture, language (Tamazight), and Amazigh identity[20,23,24,25,26]. Some studies suggest that a decline in effective population size leads to a decrease in genetic variation, reducing the substrate for purifying selection to act upon and lowering its efficacy while increasing the effect of genetic drift This would cause the accumulation of slightly deleterious alleles and homozygous derived genotypes in a higher proportion than in non-affected populations[36,37,38,43,44]. Studies about populations with a much deeper or recent effect of such demographic e vents[36,45,46] agree in the accumulation of deleterious alleles and homozygous genotypes, the increased recessive load, and a shift in variant distribution, with fewer rare and more common variants They point to relaxed purifying selection in such populations.

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Conclusion