GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach

Abstract

Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME). Among the XMEs, glutathione-S-transferases (GST) gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs). Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs). The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions) and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

Fig 1. Phylogenetic tree of 20 different continental regions population affiliations for GST M1-T1 null allele frequency.

The tree was produced by the UPGMA method from D_ST values in Table 2 and cluster with more than 50% of 1000 bootstrap replicates were included in the consensus tree obtained by Felsenstein (1989) phylogeny interference package. Major group of GST M1-T1 null allele frequencies were from population of Xhosa tribe, Zimbabwe, Ethiopia, Egypt, Afghanistan and Caucasian. Abbreviations used were same as those in Table 1.

Fig 2. Phylogenetic tree of 45 geographically assorted human populations for GST M1-T1 null allele frequency.

This tree was based on D_ST values in Table 3. Other aspects were same as those in Fig. 1. Major group of GST M1-T1 null allele frequencies were from population of Xhosa tribe, Zimbabwe, Ethiopia, Egypt, Afghanistan, Caucasian and Andhra Pradesh. Abbreviations used were same as those in Table 1.

Fig 3. Geographic Location of GST M1-T1 null allele frequency patterns in Scattered Plot.

This scenario is largely a speculation based on Nei’s D_ST based phylogenetic trees in Figs. 1 and 2, which suggest seven patterns for GST M1-T1 null allele frequency among the 45 geographically assorted human populations. The scattered plot shows the genetic affinity and geographical distribution of the seven probable patterns with three major split among the continental regions such as an “African” split with South African Xhosa pattern (I), an “out of Africa” split with East African Zimbabwe (II), East African Ethiopia (III), North African Egypt (IV) patterns and an “other than Africa” split with South Asian Afghanistan (V), West Asian Caucasian (VI), South Asian Indian Andhra Pradesh patterns (VII). Abbreviations used were same as those in Table 1.