Journal
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS
Volume 501, Issue 1-2, Pages 19-28Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/S0027-5107(01)00304-9
Keywords
mitochondrial DNA; HeLa cells; tumorigenesis; mitochondrial genetics; cancer mutations
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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. (C) 2002 Elsevier Science B.V. All rights reserved.
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