Nonneutral evolution of tandem repeats in the mitochondrial DNA control region of lagomorphs

The mitochondrial DNA of the European rabbit (Oryctolagus cuniculus)contains a tandem array of 153-bp repeats in the vicinity of thereplication origin of the H-stand. Variation among molecules in the numberof these repeats results in inter- and intraindividual length polymorphism(heteroplasmy). Generally, in an individual, one predominant molecular typeis observed, the others representing a low percentage of the mtDNA content.At the tissue level, we observe a particular distribution of thispolymorphism in the gonads compared with liver, kidneys, or brain, implyinga relationship between the differentiation status of the cells and thetypes of new mtDNA molecules which appear and accumulate during lifetime.Similar tandem repeats were also found in the mtDNA noncoding region ofEuropean hares (Lepus europaeus), a cottontail (Sylvilagus floridanus), anda pika (Ochotona rufescens). The lengths and the sequences of these unitsevolve rapidly and in a concerted way, but the number of repeats ismaintained in a narrow range, and an internal 20-bp segment is highlyconserved. Constraints restrict the evolution of the primary sequence ofthese repeated units, the number of which is probably controlled by astabilizing selection.