The mitochondrial DNA (mtDNA) control region is a highly variable segment that contains functional elements that control mtDNA transcription and replication. By analysis of the polymorphic nucleotide spectrum of that segment, we aimed to identify the most conserved sites that should be associated with these elements. For that aim, we analyzed 50 033 human mtDNA control region sequences (mtDNA positions 16 066-16 374). We identified 10 conserved tri-nucleotides, one conserved tetra-nucleotide, and one conserved penta-nucleotide, containing six repetitions of the motif CAT, and two of its complement motif ATG (p value < 2 × 10 - 4). Three other appearances of the tri-nucleotide CAT were almost perfectly preserved. The positions of the preserved CAT elements are associated with the location of previously identified termination-associated sequences (TAS) which are the binding locations for proteins involved in mtDNA replication. We, therefore, hypothesize that the CAT tri-nucleotide elements within the control region may be the binding sites for TAS proteins and are directly involved in mtDNA transcription and replication.
Keywords: D-loop; TAS; mitochondria; mtDNA control-region.