A high frequency of mtDNA polymorphisms in HeLa cell sublines.

The complete mtDNA sequences from the uncloned "founder" HeLa cells and from five sublines have been determined. These sequences all carry a common "core" of 38 single basepair alterations relative to the revised Cambridge Reference Sequence (CRS). The HeLa mitochondrial genome is of African descent and it is a member of the African L3 haplogroup. The sequence of the HeLa mtDNA resolves the uncertainty surrounding the mosaic composition of the original CRS for human mtDNA. Most importantly, we detected a total of eight polymorphisms that have arisen in the mtDNA coding region of different HeLa sublines. These observations suggest that HeLa mtDNA has a high rate of sequence divergence, relative to the phylogenetically-derived divergence rate for mtDNAs in the human population, which results from a relaxation of negative selection against the fixation of deleterious mutations. Furthermore, this high frequency of polymorphisms in HeLa mtDNA may reflect a process similar to the accumulation of somatic mtDNA mutations in human cancers. Preliminary analysis of single-cell derived subclone lines revealed the occurrence of another polymorphism and provided evidence for a large number of mtDNA segregation units.