[In silico and systematic molecular evolutionary analysis of human SIAH1b inactivation]

"Seven in absentia homolog" (SIAH) is E3 ubiquitin ligase gene. It is reported that mice have three SIAH homolog genes, Siah1a, Siah1b and Siah2, while men have SIAH1 and SIAH2 genes. It has recently been reported that, among these genes, mouse Siah1b gene is a direct target of p53. However, the nature of human "SIAH1b" gene remains unknown. In this study, we identified it on chromosome X by using a computed searching methods (in silico cloning). Using cDNA from human tissues, we attempted to amplify this region by PCR, but failed to amplify it. By analyzing the structure of human "SIAH1b" gene, we found that Alu was inserted immediately before its coding region, and that this gene had a number of base substitutions in its coding region, compared to its homolog genes in mouse or man. From these findings, we suggest that human "SIAH1b" gene had been inactivated by insertion of Alu, and estimate that the inactivation occurred about 30-58 million years ago from the substitution rates of base during evolution.