Tandem chimerism as a means to increase protein complexity in the human genome.
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.
Parra
Genís
G
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.
Reymond
Alexandre
A
Dabbouseh
Noura
N
Dermitzakis
Emmanouil T
ET
Castelo
Robert
R
Thomson
Timothy M
TM
Antonarakis
Stylianos E
SE
Guigó
Roderic
R
D050939:Gene Fusion / Q000235:genetics*; D015894:Genome, Human / Q000235:genetics*; D006801:Humans; D012326:RNA Splicing / Q000235:genetics*; D014158:Transcription, Genetic / Q000235:genetics*