Computational analysis of mitochondrial sequence diversity in human and mouse shotgun sequence data

There are approximately 1014 copies of mitochondrial DNA (mtDNA) in a human individual (Stoneking 1996). This quantity of mtDNA can be treated as a population, because mtDNA has a high mutation rate (Brown et al. 1979), so it is expected that there is a diversity of mtDNA versions in an individual. In some populations, disease mutant mtDNA, may lead to illness or death (Holt et al. 1990; Johns 1995; Larsson and Clayton 1995; Wallace 1995a & b, 1999, 2001; Chinnery and Samuels 1999; Chinnery and Turnbull 2001; Thorburn and Dahl 2001; Schmiedal et al. 2003). Mitochondria sequence diversity (MSD) was studied using a unique data set generated by Celera Genomics in the process of sequencing the human and mouse genomes (Venter et al. 2001) (Mural et al. 2002). The question of whether there are significant levels of MSD within every individual is explored. The dataset contained fragments of DNA sequence matching mitochondria) DNA, which were assembled to produce deep redundant coverage of several donors. The assemblies were analyzed to unambiguously reveal variations, which show the existence of MSD below 2%. Low level point mutations and length variations that can be difficult to detect with other sequencing methods were clearly apparent within the Celera Genomics dataset, because of the unique nature of the dataset.