Completed genome sequences have revealed that the gene number in organisms as distinct as worms, flies, and humans, does not differ dramatically. Even the same types of genes are present, in general. What may account for large morphological and behavioral differences between animal species is variation in how genes are expressed. Genes encoded in DNA must be made into working copies, called RNA, which serve as the instructions for adding the various protein building blocks (amino acids) into the growing protein chain during synthesis. In most animal genes, the part of a gene containing the instructions for making protein is broken up into pieces (exons) that must be spliced together to make a final RNA messenger. The pieces that are removed between the exons are called introns. In some cases, different exons can be shuffled together in the same gene to make instructions for different proteins- one gene can encode hundreds of proteins using this process. Another, more subtle approach, is called A-to-I RNA editing. Here, an enzyme makes a highly selective chemical change to an RNA message, changing the instructions as to the final identity of single amino acids within a protein. These edited changes can profoundly alter the functions of the edited versus unedited proteins. Curiously, almost all of the target genes recoded by this process are genes involved in rapid electrical and chemical signaling, in both flies and humans. Moreover, previous studies have shown that a substantial amount of diversity exists in between organisms in terms of the identity of gene targets for RNA editing and the specific sites themselves. Interestingly, in most cases, the information directing the process of RNA editing resides in introns, the part of a message that is not included in the final RNA blueprint and the part that is often the most variable between species. The research entailed in this project will involve the elucidation of the differences between species in the process of RNA editing in order to understand the biological role of this enigmatic process in nervous system function. Further, the project will attempt to understand species-specific differences in the enzymes that perform RNA editing, as well as the consequences of RNA editing in a certain gene target involved in chemical signaling in the brain. The basic nature of this research into gene expression in various species lends itself well to the training of undergraduates, graduate students and postdoctoral fellows.
