Molecular evolution of the CMT1A-REP region: A human- and chimpanzee-specific repeat

The CMT1A-REP repeat consists of two copies of a 24-kb sequence on human ch romosome 17p11.2-12 that flank a 1.5-Mb region containing a dosage-sensitiv e gene, peripheral nerve protein-22 (PMP22). Unequal meiotic cross over med iated by misalignment of proximal and distal copies of the CMT1A-REP in hum ans leads to a 1.5-Mb duplication or deletion associated with two common pe ripheral nerve diseases, Charcot-Marie-Tooth disease type 1A (CMT1A) and he reditary neuropathy with liability to pressure palsies (HNPP). Previous mol ecular hybridization studies with CMT1A-REP sequences suggested that two co pies of the repeat are also found in the chimpanzee, raising the possibilit y that this unique repeat arose during primate evolution. To further charac terize the structure and evolutionary synthesis of the CMT1A-REP repeat, fl uorescent in situ hybridization (FISH) analysis and heterologous PCR-based assays were carried out for a series of primates. Genomic DNA was analyzed with primers selected to differentially amplify the centromeric and telomer ic ends of the human proximal and distal CMT1A-REP elements and an associat ed mariner (MLE) sequence. All primate species examined (common chimpanzee, pygmy chimpanzee, gorilla, orangutan, gibbon, baboon, rhesus monkey, green monkey, owl monkey, and galago) tested positive for a copy of the distal e lement. In addition to humans, only the chimpanzee was found to have a copy of the proximal CMT1A-REP element. All but one primate species (galago) te sted positive for the MLE located within the CMT1A-REP sequence. These obse rvations confirm the hypothesis that the distal CMT1A-REP element is the an cestral sequence which was duplicated during primate evolution, provide sup port for a human-chimpanzee clade, and suggest that insertion of the MLE in to the CMT1A-REP sequence occurred in the ancestor of anthropoid primates.