Primate disrupted-in-schizophrenia-1 (DISC1): High divergence of a gene for major mental illnesses in recent evolutionary history

Here we analyze the species conservation of disrupted-in-schizophrenia-1 (DISC1) gene, a susceptibility gene for schizophrenia. We cloned cDNA of DISCI and characterized DISCI protein in monkey brains and compared their features with those in a variety of species, including humans, rodents and lower vertebrates. Sequences of human and monkey DISCI are very similar for both nucleotides and amino acids, in sharp contrast to those of rodents; this is reminiscent of G72, another gene involved in major mental illnesses. Bioinformatic cross-species comparisons identified a portion of DISC] sequences in chicken and Caenorhabditis elegans, but failed to find DISC1 in Drosophila. In contrast to sequence differences, the regional expression profile of DISCI is well conserved between rodents and primates in that levels of DISC I mRNA and protein are higher in the hippocampus and the cerebral cortex, and much lower in cerebellum in adult brains. The findings of this study may suggest overall patterns of evolution of genes for psychiatric disorders, and thus assist in production of genetically-engineered mice, and the interpretation of the underlying mechanisms of psychiatric conditions. Published by Elsevier Ireland Ltd on behalf of Japan Neuroscience Society.