SKEWED SEGREGATION OF THE MTDNA NT-8993 (T-]G) MUTATION IN HUMAN OOCYTES

Rapid changes in mtDNA variants between generations have led to the bo ttleneck theory, which proposes a dramatic reduction in mtDNA numbers during early oogenesis. We studied oocytes from a woman with heteropla smic expression of the mtDNA nt 8993 (T-->G) mutation. Of seven oocyte s analyzed, one showed no evidence of the mutation, and the remaining six had a mutant load >95%. This skewed expression of the mutation in oocytes is not compatible with the conventional bottleneck theory. A p ossible explanation is that, during amplification of mtDNA in the deve loping oocyte, mtDNA from one mitochondrion is preferentially amplifie d. Thus, subsequent mature oocytes may contain predominantly wild-type or mutant mitochondrial genomes.