Complex arrangement of genes within a 220-kb region of double-duplicated DNA on human 2q37.1

Gene duplication events are followed by divergence of initially identical g ene copies, due to the subsequent accumulation of mutations. These mutation s tend to be degenerative and may lead to either non-functionalization or s ubfunctionalization of the gene copies. Here we report the molecular charac terization of a 220-kb genomic DNA fragment from human 2q37.1, in which a d ouble duplication and a partial triplication event has taken place. As a re sult, this region contains four copies of alkaline phosphatase (P), four co pies of the ECEL1 gene (X), two copies of a newly identified gene (N), and two copies of a cholinergic receptor subunit (R), in the order N-P-X-P-X-P- X-N-P-X-R-R. While three of the four ECEL1 copies, one copy of the phosphat ase gene and one copy of the newly identified gene have lost their function , three phosphatase gene copies and the two receptor subunits are still fun ctionally active and thus may provide an example for subfunctionalization o f duplicated genes. (C) 2001 Academic Press.