Structural elements highly preserved during the evolution of the D-loop-containing region in vertebrate mitochondrial DNA

Abstract

A detailed comparative study of the regions surrounding the origin of replication in vertebrate mitochondrial DNA (mtDNA) has revealed a number of interesting properties. This region, called the D-loop-containing region, can be divided into three domains. The left (L) and right (R) domains, which have a low G content and contain the 5' and the 3' D-loop ends, respectively, are highly variable for both base sequence and length. They, however, contain thermodynamically stable secondary structures which include the conserved sequence blocks called CSB-1 and TAS which are associated with the start and stop sites, respectively, for D-loop strand synthesis. We have found that a "mirror symmetry" exists between the CSB-1 and TAS elements, which suggests that they can act as specific recognition sites for regulatory, probably dimeric, proteins. Long, statistically significant repeats are found in the L and R domains. Between the L and R domains we observed in all mtDNA sequences a region with a higher G content which was apparently free of complex secondary structure. This central domain, well preserved in mammals, contains an open reading frame of variable length in the organisms considered. The identification of common features well preserved in evolution despite the high primary structural divergence of the D-loop-containing region of vertebrate mtDNA suggests that these properties are of prime importance for the mitochondrial processes that occur in this region and may be useful for singling out the sites on which one should operate experimentally in order to discover functionally important elements.

Structure and Evolution of the Mitochondrial DNA Complete Control Region in the Lizard Lacerta dugesii (Lacertidae, Sauria)

“…Four motifs matching the TAS element (5 0 ...AATTACA...3 0 ) reported by Saccone et al (1987), as well as the more expanded sequence denominated ETAS (Sbisa`et al 1997), are evident (Fig. 4), but three of them are in an inverted direction from that of Saccone et al (1987). The conservative nature of these sequences and the flanking regions provides additional evidence that they may be of importance for mitochondrial transcription and regulation in the D-loop-containing region Saccone et al 1987;Sbisa`et al 1997).…”

“…4). Four motifs matching the TAS element (5 0 ...AATTACA...3 0 ) reported by Saccone et al (1987), as well as the more expanded sequence denominated ETAS (Sbisa`et al 1997), are evident (Fig. 4), but three of them are in an inverted direction from that of Saccone et al (1987).…”

“…4), but three of them are in an inverted direction from that of Saccone et al (1987). The conservative nature of these sequences and the flanking regions provides additional evidence that they may be of importance for mitochondrial transcription and regulation in the D-loop-containing region Saccone et al 1987;Sbisa`et al 1997). The four TAS elements do not seem to be randomly distributed in the CR since they are found in the extremities and in conserved regions.…”

“…The CR spans between the tRNA Phe and the tRNA Pro genes and includes the transcription initiation sites for both strands (Attardi 1985;Clayton 1982;Saccone et al 1987). Because the CR lacks typical coding constraints, it accumulates base substitutions, indels, and a variable number of tandem repeats which are responsible for the extensive size variation found in the mtDNA molecule (Hoelzel et al 1994;Sbisa`et al 1997).…”

Sequence variation and structural conservation in the D-loop region and flanking genes of mitochondrial DNA from Japanese pond frogs.

“…Because of the short regulatory elements it contains and its propensity for rapid change, the D-loop region is one of the most interesting parts of the vertebrate mitochondrial genome. Several detailed comparisons of the D-loop region in mammalian mtDNA have been published (Brown et al, 1986;Saccone et al, 1987Saccone et al, , 1991Hoelzel et al, 1991). Substantial length variation has been found in the D-loop region of many mammalian and fish mtDNA (Moritz et al, 1987: Rand, 1993.…”