POSTER NO: 558

Length Variaton of Thymidylate Synthase Enhancher Region (TSER) and Their Evolution in Primates

Hui-Rong Luo, Yun-Wu Zhang, Ya-Ping Zhang
Kunming Institute of Zoology, Chinese Academy of Sciences, Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, P. R. China

Thymidylate synthase (TS) (EC2.1.1.45) catalyzes the reductive methylation of dUMP during the synthesis of dTMP and is essential in regulating a balanced supply of the four DNA precursors for DNA replication. It has been reported that the 5'-ternimal regulatory region of the human thymidylate synthase (TS enchancer region, TSER) is polymorphic, containing two, three, four, five or nine tandemly repeated copies of 28bp sequence in different populations. This unusual repeat sequence structure has been found in rhesus, but not in rodents, suggesting it originated as a result of duplication or of duplication followed by deletion of the TSER during evolution from rodents to primates. To further our understanding of the origin of this region, we investigated length variation of TSER within and among primate species by sequencing, and compared the results with that of humans. We amplified and sequenced TSER in different primates, including hominoids; two subfamilies of Old World monkeys (OWMs): colobines and cercopithecines; and two species of New World monkeys (NWMs). Besides in humans, we also found TSER length difference polymorphisms exist in some primate populations, although in other primate populations, this region has been fixed. Alleles with one, two, three, or four copies of the repeat motif were identified in different primates. Double and triple tandem repeats are two dominant allele types in hominoids and OWMs. Three unique repeat motifs were identified and defined. We defined each repeat motif of the Most Recent Common Ancestor (MRCA) of hominoids and OWMs as R1, R2, and R3, respectively, started from the 3'-end. In most primates, the three repeat motifs are indirectionally tandem with a pattern of 5'-R3R2R1-3'. Each repeated motif is affordable to be lost. Slipped-strand mispairing are responsible for most length variations in TSER; and it seems interchromosomal recombination also occurred in this region, creating a new allele type *3+1.