The GC clusters of the mitochondrial genome of yeast and their evolutionary origin

We have studied the primary and secondary structures, the location and the orientation of the 196 GC clusters present in the 90% of the mitochondrial genome of Saccharomyces cerevisiae which have already been sequenced. The vast majority of GC clusters is located in intergenic sequences (including ori sequences, intergenic open reading frames and the gene varl which probably arose from an intergenic spacer) and in intronic closed reading frames (CRF's); most of them can be folded into stem-and-loop systems; both orientations are equally frequent. The primary structures of GC clusters permit to group them into eight families, seven of which are related to the family formed by clusters A, B and C of the ori sequences. On the basis of the present work, we propose that the latter derive from a primitive ori sequence (probably made of only a monomeric cluster C and its flanking sequences r* and r) through (i) a series of duplication inversions generating clusters A and B; and (ii) an expansion process producing the AT stretches of ori sequences. Most GC clusters apparently originated from primary clusters also derived from the primitive ori sequence in the course of its evolution towards the present ori sequences. Finally, we propose that the function of GC clusters is predominantly, or entirely, associated with the structure and organization of the mitochondrial genome of yeast and, indirectly, with the regulation of its expression.