The main regulatory region of mammalian mitochondrial DNA: Structure-function model and evolutionary pattern

Abstract

The evolution of the main regulatory region (D-loop) of the mammalian mitochondrial genome was analyzed by comparing the sequences of eight mammalian species: human, common chimpanzee, pygmy chimpanzee, dolphin, cow, rat, mouse, and rabbit. The best alignment of the sequences was obtained by optimization of the sequence similarities common to all these species. The two peripheral left and right D-loop domains, which contain the main regulatory elements so far discovered, evolved rapidly in a species-specific manner generating heterogeneity in both length and base composition. They are prone to the insertion and deletion of elements and to the generation of short repeats by replication slippage. However, the preservation of some sequence blocks and similar cloverleaf-like structures in these regions, indicates a basic similarity in the regulatory mechanisms of the mitochondrial genome in all mammalian species. We found, particularly in the right domain, significant similarities to the telomeric sequences of the mitochondrial (mt) and nuclear DNA of Tetrahymena thermophila. These sequences may be interpreted as relics of telomeres present in ancestral linear forms of mtDNA or may simply represent efficient templates of RNA primase-like enzymes. Due to their peculiar evolution, the two peripheral domains cannot be used to estimate in a quantitative way the genetic distances between mammalian species. On the other hand the central domain, highly conserved during evolution, behaves as a good molecular clock. Reliable estimates of the times of divergence between closely and distantly related species were obtained from the central domain using a Markov model and assuming nonhomogeneous evolution of nucleotide sites.

Comparison of evolutionary rates in the mitochondrial DNA cytochrome b gene and control region and their implications for phylogeny of the Cobitoidea (Teleostei: Cypriniformes)

“…Saunders and Edwards (2000) studied dynamics and phylogenetic implications of mtDNA CR sequences in the New World Jays and found a slow rate of evolution in the CR. They suggested that their data indicated a higher Studies have showed that CR contains sequences related to termination of H-strand replication, the origin of H-strand, and promoters of transcription to both L-and H-strand (Doda et al, 1981;Randi and Lucchini, 1998;Saccone et al, 1991;Sbisà et al, 1997;Southern et al, 1988). This indicates that the CR has evolutionary constraints.…”

Genetic aspects of mitochondrial genome evolution

“…Replication of insect mtDNA is extremely asymmetric. Since the structure of the control region in mammals/chordates (Sbisá et al, 1997;Saccone et al, 1991) and insects (Saito et al, 2005;Zhang and Hewitt, 1997) is very different it is unclear at present whether the same mechanisms are responsible for initiation and termination of replication throughout the Metazoa.…”

Structure and genetic variation of the mitochondrial control region in the honey bee Apis mellifera

“…It is widely used for genetic inferences especially in mammals where it is also known as the D-loop (for displacement-loop), a three-stranded structure that forms during replication of the molecule. At least in vertebrates, functional structures within this region have been identified across a wide number of species namely highly conserved sequences associated with the molecule replication, conserved and variable blocks, as well as palindromic and stable cloverleaf structures that may be involved in the replication of the molecule as well as transcription initiation sites for each strand (Chang and Clayton 1984;Saccone et al 1991;Clayton 1982Clayton , 1996. In invertebrates, the control region is much less studied and understood.…”