Mitochondrial DNA deletions in human cardiac tissue show a gross mosaic distribution

The variability of mitochondrial DNA (mtDNA) deletional patterns has been i nvestigated in adjacent slices of human heart atrium. Using quantitative PC R we found differential abundances of one particular mtDNA deletion, that o f 4977 bp (mtDNA(4977)), among sets of adjacent slices of right atrial trab eculae pectinatae from 10 subjects. Some subjects had relatively constant a bundance of mtDNA(4977) among the tissue slices, while others covered a wid e range. A qualitative PCR procedure was used to visualize the patterns of multiple deletions within an 8.64-kb segment of the mtDNA genome, in the sa me set of atrial trabeculae samples. Some subjects showed completely differ ent multiple deletional patterns in each of the trabeculae slices analyzed. There was no correlation between the variation of the abundance of mtDNA(4 977) and that of the multiple deletions. The results are consistent with th e notion that the occurrence of mtDNA deletions during aging isa random pro cess, involving their production throughout the Lifetime of an individual. In this view, the patterns of new deletions are superimposed on those alrea dy accumulated by propagation and segregation of mutations formed earlier i n life. (C) 1999 Academic Press.