Mitochondrial genome consensus sequence for the South African Khoi–San population

Abstract

Maternal inheritance and the absence of recombination have contributed to mitochondrial deoxyribonucleic acid (mtDNA) being utilised to study human evolution. This, together with an increased mutation rate in mtDNA, provides information about the most recent common ancestor of modern humans. Previous studies suggested that Africa harbours the highest mtDNA diversity, supporting an out-of-Africa hypothesis for modern human evolution. From subsequent studies it was suggested that the Khoi-San population, in particularly the !Kung, cluster at the deepest root of the global phylogenetic tree. The Cambridge reference sequence is used worldwide in mitochondrial studies as a reference. However, recent studies have observed discrepancies from this sequence, which were confirmed by reanalysis. During this investigation the complete mitochondrial sequences of 13 !Kung individuals were determined. From phylogenetic analyses their clustering in the African LO-Iineage was revealed. The evolutionary rate of the derived sequences was investigated through statistical analysis and the hypothesis of neutral evolution was rejected. Pairwise nucleotide distribution suggested that sequences representing haplogroups LO, L 1 and L2 are examples of populations that were of stable population size for a long time. However, L3 was suggested to have been subjected to population expansion, in support of the out-of-Africa theory of evolution. From the comparative analysis of the 13 !Kung sequences with an LO-specific haplogroup tree it was observed that the 13 individuals clustered in two main groups. Ten individuals were added to one branch of the phylogenetic tree, revealing further branching, while three individuals were added to the terminal branches of another tree topology. A consensus sequence was derived from the 13 Khoi-San sequences, which was 99.25% similar to each of the sequences. This sequence could be utilised to investigate evolution of the mitochondrial genome over time as well as to evaluate the pathogenicity of mutations in patients.