Comparison of complete mitochondrial genome sequence between different ethnic groups from Southern Africa

Abstract

The human mitochondrial genome is a 16,569 base pair double-stranded deoxyribonucleic acid (DNA) molecule located in the mitochondrion. The mitochondria1 genome sequence is conserved, maternally inherited and undergoes no recombination, making its evaluation ideal for evolutionary studies. Certain alterations in the genome are unique to specific human populations and haplogroups. The genetic background, or haplogroup of an individual, may act in concert with disease associated mutations. The ethnicity of an individual is often utilised as an indicator of haplogroup. During this investigation the full mitochondrial sequence of 10 individuals belonging to three ethnic Southern African populations, namely three Xhosa, three Zulu and four Tswana individuals, was generated. The complete nucleotide sequences were compared to one another in order to determine the genetic relationship between individuals. Sequences were also evaluated against the 2001 revised Cambridge reference sequence (RCRS) to detect novel alterations as well as alterations present in all individuals analysed. A total of 222 alterations (207 previously reported, 15 unreported) were detected relative to the RCRS. Five length alterations and 207 nucleotide substitutions were detected. Ninety-eight alterations were detected only once, and 115 were detected in at least two individuals. Haplogroup analysis clustered individuals into haplogroups LO, L2 and L3. No clear correlation between haplogroup assignment and ethnic origin could be observed. The distribution of shared alterations between individuals was in agreement with the haplogroup clustering. Ethnicity can therefore not be utilised as an indicator of haplogroup in the context of the current study. To investigate the association between disease presentation and haplogroup, individuals will have to be randomly sampled and then haplogrouped. Reasons to substantiate the lack of association between ethnicity and haplogroups include the occurrence of gene flow between populations, inaccurate ethnic and incomplete haplogroup classification and populations not being sufficiently divergent.