Comparison of P 450 s from human and fugu : 420 million years 4 of vertebrate P 450 evolution

9 The fugu (pufferfish) genome has been sequenced, and a second genome assembly was released 17 May 2002. Exhaustive searches 10 were made to identify all P450 genes and pseudogenes from the earlier release of 26 October 2001. P450 genes assembled as 11 completely as possible from these data were used to do additional searches of the newer assembly and all P450 genes and pseud12 ogenes in the available fugu sequence data have been identified, compared to human P450s, and assigned names. There are 54 P450 13 genes in fugu and 1 nearly intact pseudogene (CYP3A50P). CYP1A is missing much of its N-terminal half; however, 45 P450 genes 14 are completely assembled. Eight others are lacking only one or two exons or less. CYP2X4 is known only from an EST. This may be 15 a 55th P450 gene if it represents an accurate sequence. In addition to 2X4, there are 16 other pseudogene fragments or small pieces of 16 P450 genes. At the P450 family level, 17 of 18 mammalian families are found in fugu. CYP39 is the only CYP family missing and it is 17 not seen in any other fish sequence data either. The CYP2 family shows the largest degree of divergence. In the CYP2 family, only 18 CYP2R1 and CYP2U1 are conserved as recognizable subfamilies across species. Intron–exon boundaries are largely preserved 19 across 420 million years of evolution. 2