Preferential amplification and phenotypic selection in a population of deleted and wild-type mitochondrial DNA in cultured cells.

Autor: Spelbrink, J. N., Zwart, Rob, Van Galen, Mieke J. M., Van den Bogert, C.
Zdroj: Current Genetics; Sep1997, Vol. 32 Issue 2, p115-124, 10p
Abstrakt: In order to study the still poorly understood dynamics of mitochondrial gene segregation, we attempted to alter the percentage of deleted mtDNA (del-mtDNA) over wild-type mtDNA in cell-culture by manipulating respiratory chain capacity. For this purpose, we used a cell-line harbouring a 6-kb mtDNA-deletion which normally was present in 70% of the molecules. The results show that in the presence of low concentrations of doxycycline (DC), an inhibitor of mitochondrial protein synthesis, the average percentage of del-mtDNA in culture steadily declined. After short-term DC treatment most cells still contained del-mtDNA and removal of DC led to a rapid increase in the proportion of del-mtDNA. In contrast, long-term DC treatment rendered del-mtDNA undetectable by Southern analysis, reflecting the complete absence of del-mtDNA in most cells. In this case, del-mtDNA in culture remained at a constant low level after removal of the drug. The results clearly show the importance of phenotypic selection in the segregation of a deleterious mtDNA mutation. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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