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.
Herrnstadt
Corinna
C
MitoKor, 11494 Sorrento Valley Road, San Diego, CA 92121, USA.
Preston
Gwen
G
Andrews
Richard
R
Chinnery
Patrick
P
Lightowlers
Robert N
RN
Turnbull
Douglass M
DM
Kubacka
Iwona
I
Howell
Neil
N
D001483:Base Sequence; D004272:DNA, Mitochondrial / Q000235:genetics*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic
D004272:DNA, Mitochondrial