Outlier maternal haplogroups N5 and X2 and their potential role in elevated tuberculosis prevalence among the...

India bears the largest burden of tuberculosis (TB) cases in the world. Prior studies have highlighted significantly higher pulmonary TB among the Sahariya tribal population in Central India. The disease susceptibility of a population to disease may be influenced by genetic ancestry. In this context, we investigated the maternal genetic ancestry of the Sahariya in relation to their neighbouring tribal populations. For this study, we used the largest available dataset (n = 729), comprising 140 Sahariya individuals and 589 individuals from adjacent caste and tribal groups (including 50 newly sequenced samples). Our detailed mtDNA analysis revealed the exclusive presence of two rare haplogroups N5 and X2 which are completely absent in neighbouring tribal and caste populations. Further examination of the phylogeographic origins of the branches of haplogroups N5 and X2 suggests that these unique founder haplogroup branches (N5a and X2a) were likely introduced into the Sahariya from the western regions of the Indian subcontinent. The temporal expansion of these haplogroups indicates a gene flow from the western area to the Sahariya population during the early Iron Age. In addition to that, we have also analysed 33 SNPs for six TB-associated genes. We observed a single SNP (rs4958847-IRGM1) where the minor allele frequency was significantly different in Sahariya with their neighbouring populations. Consequently, our analysis of maternal genetic ancestry and known associated autosomal genes provides insights that may help explain the higher prevalence of TB among the Sahariya compared to their neighbouring populations.