Construction of a mitochondrial consensus sequence for the Khoi-San population of Southern Africa

Abstract

The revised Cambridge Reference Sequence (rCRS) is used as a standard for the human mitochondrial DNA (mtDNA) sequence in studies of human evolution and the identification of disease-causing mutations. Due to the large number of differences observed between the rCRS and mitochondrial sequences obtained from individuals of African descent, it is frequently difficult to differentiate between alterations that are population-specific or have possible pathological significance. To address this problem, two human consensus sequences consisting of mitochondrial sequences from different continents and different haplogroups have been constructed. However, combining data from different continents and haplogroups led to a loss of variation in the human mitochondrial consensus sequences. This can be countered by using an African reference sequence, of which two sequences are currently available, namely NC_001807 (L3a1) and D38112 (L0c2). However, these sequences are not representative of the most ancient African populations (i.e. hunter-gatherers) or haplogroups (i.e. L0). In the current investigation, the complete mitochondrial genome sequences of 30 Khoi-San individuals from southern Africa were determined. Twenty-two of these Khoi-San sequences, which belong to the L0a and L0b sub-haplogroups, were combined with 13 L0 Khoi-San sequences generated previously to compile a consensus sequence for the Southern African Khoi-San population. This Khoi-San consensus sequence will represent the first example of an African population-specific consensus sequence. The results presented in the current investigation provide support for previous findings regarding the existence of a high level of genetic variation in the mtDNA of the Khoi-San population, as well as the ancient character of the Khoi-San population. In addition, it offers novel insights into the complexity of the L0 haplogroup within the Khoi-San population and the African population as a whole. The high level of genetic variation and increased age of mtDNA lineages in the Southern African Khoi-San population compared to other populations, support the use of the Khoi-San consensus sequence, alone or in conjunction with the rCRS, as a standard in studies of human evolution and mitochondrial disease.