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Letter

Tandem chimerism as a means to increase protein complexity in the human genome

¹ Grup de Recerca en Informàtica Biomèdica, Institut Municipal d'Investigació Mèdica-Universitat Pompeu Fabra, and Programa de Bioinformàtica i Genòmica, Centre de Regulació Genòmica, E08003 Barcelona, Catalonia, Spain , ² Department of Genetic Medicine and Development, University of Geneva Medical School and University Hospitals of Geneva, 1211 Geneva, Switzerland , ³ Center for Integrative Genomics, University of Lausanne, CH-1015 Lausanne, Switzerland , ⁴ Population and Comparative Genomics, The Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, CB10 1SA Cambridge, United Kingdom , ⁵ Department of Molecular and Cellular Biology, Institut de Biologia Molecular de Barcelona, CSIC, E08034 Barcelona, Catalonia, Spain

The "one-gene, one-protein" rule, coined by Beadle and Tatum, has been fundamental to molecular biology. The rule implies that the genetic complexity of an organism depends essentially on its gene number. The discovery, however, that alternative gene splicing and transcription are widespread phenomena dramatically altered our understanding of the genetic complexity of higher eukaryotic organisms; in these, a limited number of genes may potentially encode a much larger number of proteins. Here we investigate yet another phenomenon that may contribute to generate additional protein diversity. Indeed, by relying on both computational and experimental analysis, we estimate that at least 4%-5% of the tandem gene pairs in the human genome can be eventually transcribed into a single RNA sequence encoding a putative chimeric protein. While the functional significance of most of these chimeric transcripts remains to be determined, we provide strong evidence that this phenomenon does not correspond to mere technical artifacts and that it is a common mechanism with the potential of generating hundreds of additional proteins in the human genome.

Article published online ahead of print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.4145906.

⁶ Corresponding author.
E-mail rguigo{at}imim.es; fax 34 932 240 875.

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