EVOLUTION OF A REPEAT SEQUENCE IN THE PARATHYROID HORMONE-RELATED PEPTIDE GENE IN PRIMATES

A polymorphism of the variable number of tandem repeat (VNTR) type is located 97 bp downstream of exon VI of the parathyroid hormone-related peptide (PTHrP) gene in humans. The repeat unit has the general seque nce G(TA)(n)C, where n equals 4-11. In order to characterize the evolu tionary history of this VNTR, we initially tested for its presence in 13 different species representing four main groups of Living primates. The sequence is present in the human, great apes, and Old World monke ys, but not in New World monkeys; and this region failed to PCR amplif y in the Loris group. Thus, the evolution of the sequence as part of t he PTHrP gene started at least 25-35 millions years ago, after diverge nce of the Old World and New World monkeys, but before divergence of O ld World monkeys and great apes and humans. The structural changes occ urring during evolution are characterized by a relatively high degree of sequence divergence. In general, the tandem repeat region tends to be longer and more complex in higher primates with the repeat unit mot ifs all being based on a TA-dinucleotide repeat sequence. Intra-specie s variability of the locus was demonstrated only in humans and gorilla . The divergence of the TA-dinucleotide repeat sequence and the variab le mutation rates observed in different primate species an in contrast to the relative conservation of the flanking sequences during primate evolution. This suggests that the nature of the TA-dinucleotide repea t sequence, rather than its flanking sequences, is responsible for gen erating variability. Particular features of the sequence may allow it to form stable secondary structures during DNA replication, and this, in turn, could promote slipped-strand mispairing to occur.