Heterogeneous mitochondrial DNA D-loop sequences in bovine tissue

Mitochondrial DNA from bovine tissue contains heterogeneous sequences located within an evolutionary conserved cytosine homopolymer sequence near the 5′ end of the D-loop region. This part of the mammalian mitochondrial genome is known to contain the origin of heavy strand DNA synthesis and the major transcriptional promoter for each strand. Nucleotide sequence analysis of cloned DNA and electrophoretic analysis of appropriate small fragments from animal tissue reveal a population of length polymorphs containing from nine to 19 cytosine residues. No individual length species represents more than 40% of the population. These data imply a state of significant intraanimal mtDNA sequence heterogeneity, which most likely occurs intracellularly as well. The localization of variability to a homopolymer run suggests that replication slip-page generated the sequence population. We also report that when recombinant clones containing this region are repeatedly passaged in E. coli, they begin to regenerate length variation similar to that seen in animal mtDNA.