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 DISC1 and characterized DISC1 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 DISC1 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 DISC1 sequences in chicken and Caenorhabditis elegans, but failed to find DISC1 in Drosophila. In contrast to sequence differences, the regional expression profile of DISC1 is well conserved between rodents and primates in that levels of DISC1 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.
Bord
Lyuda
L
Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
Wheeler
Jeff
J
Paek
Matthew
M
Saleh
Masoumeh
M
Lyons-Warren
Ariel
A
Ross
Christopher A
CA
Sawamura
Naoya
N
Sawa
Akira
A
D000595:Amino Acid Sequence; D000818:Animals; D015153:Blotting, Western / Q000379:methods; D001921:Brain / Q000378:metabolism; D002645:Chickens; D003001:Cloning, Molecular / Q000379:methods; D019143:Evolution, Molecular; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D008253:Macaca mulatta; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D011323:Primates / Q000235:genetics*; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D016415:Sequence Alignment; D023741:Takifugu; D015027:Zebrafish
C498794:Disc1 protein, mouse; C498795:Disc1 protein, rat; D009419:Nerve Tissue Proteins