Beyond the Identification of Transcribed Sequences:
Functional, Evolutionary and Expression Analysis
12th International Workshop
October 25-28, 2002
Washington, DC

List of Abstracts * Speakers * Organizers * Authors * Original Announcement

C. elegans Operons: A Novel Tool to Find Functionally Related Genes

Tom Blumenthal
Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine, Denver, CO 80262

C. elegans and its close relatives appear to be unique among animals in having large numbers of polycistronic transcription units, not unlike bacterial operons. These operons may constitute an important gene finding tool. Although the genes in these operons are eventually represented on monocistronic mRNAs, they are transcribed as a polycistronic precursor that is processed into gene-length units by trans-splicing and 3 end formation. We have recently completed a microarray analysis of all predicted and known C. elegans genes to determine which genes are contained in operons (Blumenthal et al., 2002, Nature 417:851). Our results indicate that ~15% of all C. elegans genes are in operons ranging from 2 to 8 genes long. We have been analyzing the list of ~1000 operons, containing ~2,600 genes to determine what types of genes they contain and, importantly, to what extent functionally-related genes are co-transcribed in operons.

Whereas some classes of genes are very highly represented in operons, others are almost never in operons, suggesting they are not random gene assemblages. For example, ~50% of genes whose products are destined for the mitochondria are transcribed in operons. Similarly, around half of genes that encode the basic transcription, splicing and translation machinery are in operons. In sharp contrast, transcription factor genes are virtually never in operons. Also, genes that are highly regulated in a particular tissue are generally excluded from operons. These include genes for collagens, sperm proteins, intermediate filament proteins, cytochrome P450s, immunoglobulin domain proteins and basement membrane proteins. It seems as if proteins can be transcribed as parts of operons if they are either not regulated or need to be globally regulated in response to certain kinds of signals.

Many of the C. elegans operons do not appear to make any kind of functional sense. On the other hand, many others do. There are numerous operons that contain more than one gene encoding proteins that are part of the basic transcription machinery, and this occurs far more often than would be expected by chance. This is also true of the splicing machinery and of mitochondrial proteins. Furthermore, there are operons that contain a subunit of one of the RNA polymerases and one of the basic factors that act with that polymerase. The operon list can suggest many previously unsuspected functional relationships among proteins, but whether most operons involve functionally related genes is not yet known. Many homologs of human disease genes are contained in operons, and determining whether the products of the other genes in these operons are related proteins is worth investigating.

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