PgmNr D217: When One Plus One Does Not Equal Two: Some Tandem Gene Duplicates are Overactive.

Authors:
David W. Loehlin; Sean B. Carroll


Institutes
University of Wisconsin-Madison, Madison, WI.


Keyword: other ( duplication )

Abstract:

Tandem gene duplication is an important mutational process in evolutionary adaptation and human disease. Hypothetically, two tandem gene copies should produce twice the output of a single gene, but this expectation has not been rigorously investigated. Here, we show that tandem duplication often results in more than double the gene activity. A naturally occurring tandem duplication of the Alcohol dehydrogenase (Adh) gene exhibits 2.6-fold greater expression than the single copy gene in transgenic Drosophila. This tandem duplication also exhibits greater activity than two copies of the gene in trans, demonstrating that it is the tandem arrangement and not copy number that is the cause of overactivity. We also show that tandem duplication of an unrelated synthetic reporter gene is overactive (2.3- to 5.1-fold) at all sites in the genome that we tested, suggesting that overactivity could be a general property of tandem gene duplicates. Overactivity occurs at the level of RNA transcription, and therefore tandem duplicate overactivity appears to be a novel form of position effect. The increment of surplus gene expression observed is comparable to many regulatory mutations fixed in nature, and if typical of other genomes, would broadly shape the fate of tandem duplicates in evolution.



Flybase Genetic Index:
1. FlyBase gene symbol: Adh; FBgn: FBgn0000055