The south of Tunisia is characterized by marked ethnic diversity, highlighted by the
coexistence of native Berbers with Blacks, Jews and Arab-speaking populations. Despite
this heterogeneity, genetic anthropology studies investigating the origin of current
Southern Tunisians were rarely reported. We examined human leukocyte antigen (HLA)
class I (A, B) and class II (DRB1, DQB1) gene profiles of 250 unrelated Southern Tunisians,
and compared them with those of Arab-speaking communities, along with Mediterranean
and sub-Sahara African populations using genetic distances, neighbor-joining dendrograms,
correspondence and haplotype analysis. In total, 137 HLA alleles were detected, which
comprised 32 HLA-A, 52 HLA-B, 32 DRB1 and 21 DQB1 alleles. The most frequent alleles
were HLA-A*02:01(18.02%), HLA-B*50:01 (9.11%), HLA-DRB1*07:01 (22.06%) and HLA-DQB1*02:01
(17.21%). All pairs of HLA loci show significant linkage disequilibrium. The four
loci depict negative Fnd (the normalized deviate of the homozygosity) values indicating
an overall trend to balancing selection. Southern Tunisians appear to be closely related
to others Tunisian populations including Berbers, North Africans and Iberians. On
the contrary, Southern Tunisians were distinct from Palestinian, Lebanese and Jordanian
Middle Eastern Arab-speaking population, despite the deep Arab incursions and Arabization
that affected Southern Tunisia. In addition, Southern Tunisians were distant from
many sub-Saharan communities, evidenced by genetic distance analysis. Collectively,
this indicates a limited genetic contribution of Arab invasion and Black caravans
on the makeup of Southern Tunisian gene pool.