Duplication and diversification of the apolipoprotein CI (APOCI) genomic segment in association with retroelements

We have previously shown that several multicopy gene families within the ma jor histocompatibility complex (MHC) arose from a process of segmental dupl ication. It has also been observed that retroelements play a role in genera ting diversity within these duplicated segments. The objective of this stud y was to compare the genomic organization of a gene duplication within anot her multicopy gene family outside the MHC. Using new continuous genomic seq uence encompassing the APOE-CII gene cluster, we show that APOCI and its ps eudogene, APOCI', are contained within large duplicated segments which incl ude sequences from the hepatic control region (HCR). Flanking Alu sequences are observed at both ends of the duplicated unit, suggesting a possible ro le in the integration of these segments. As observed previously within the MHC, the major differences between the segments are the insertion of sequen ces (approximately 200-1000 bp in length), consisting predominantly of Alu sequences. Ancestral retroelements also contribute to the generation of seq uence diversity between the segments, especially within the 3' poly(A) trac t of Alu sequences. The exonic and regulatory sequences of the APOCI and HC R loci show limited sequence diversity, with exon 3 being an exception. Fin ally, the typing of pre- and postduplication Alus from both segments indica tes an estimated time of duplication of approximately 37 million years ago (mya), some time prior to the separation of Old and New World monkeys.