Heteroplasmic segregation associated with trisomy-9 in cultured human cells.
In cybrid cells carrying the mitochondrial A3243G MELAS mutation, which were also heteroplasmic for the G12300A suppressor mutation, we observed a transient episode of heteroplasmic instability, resulting in a wide diversification in G12300A heteroplasmy levels and a shift in the average heteroplasmy level from 11 to 29%. These cells were found to be trisomic for chromosome 9, whereas a minority of cells that retained disomy-9 showed no instability. Coculture experiments implied that trisomy-9 cells exhibited a significant growth advantage, but neither heteroplasmy levels, respiratory phenotype nor trisomy-9 itself had direct selective value under standard culture conditions. Mitochondrial nucleoid number was the same (50-100) in cells that had or had not experienced transient heteroplasmic instability, but 1-2 orders of magnitude less than the segregation number in such cells. These findings support the idea that mtDNA partition is under nuclear genetic control, and implicate a locus on chromosome 9 in this regulation.
Lehtinen
S K
SK
Institute of Medical Technology and Tampere University Hospital, University of Tampere, FIN-33014, Finland.
Spelbrink
J N
JN
Jacobs
H T
HT
D002478:Cells, Cultured; D002899:Chromosomes, Human, Pair 9; D018920:Coculture Techniques; D004272:DNA, Mitochondrial / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D017241:MELAS Syndrome / Q000235:genetics; D009154:Mutation; D016133:Polymerase Chain Reaction; D014314:Trisomy
D004272:DNA, Mitochondrial