Transcription-mediated gene fusion in the human genome

  1. Pinchas Akiva1,2,3,
  2. Amir Toporik1,3,
  3. Sarit Edelheit1,
  4. Yifat Peretz1,
  5. Alex Diber1,
  6. Ronen Shemesh1,
  7. Amit Novik1, and
  8. Rotem Sorek1,4,5
  1. 1 Compugen Ltd., Tel Aviv 69512, Israel
  2. 2 Faculty of Life Sciences, Bar Ilan University, Ramat Gan 52900, Israel

Abstract

Transcription of a gene usually ends at a regulated termination point, preventing the RNA-polymerase from reading through the next gene. However, sporadic reports suggest that chimeric transcripts, formed by transcription of two consecutive genes into one RNA, can occur in human. The splicing and translation of such RNAs can lead to a new, fused protein, having domains from both original proteins. Here, we systematically identified over 200 cases of intergenic splicing in the human genome (involving 421 genes), and experimentally demonstrated that at least half of these fusions exist in human tissues. We showed that unique splicing patterns dominate the functional and regulatory nature of the resulting transcripts, and found intergenic distance bias in fused compared with nonfused genes. We demonstrate that the hundreds of fused genes we identified are only a subset of the actual number of fused genes in human. We describe a novel evolutionary mechanism where transcription-induced chimerism followed by retroposition results in a new, active fused gene. Finally, we provide evidence that transcription-induced chimerism can be a mechanism contributing to the evolution of protein complexes.

Footnotes

  • [Supplemental material is available online at www.genome.org.]

  • Article published online ahead of print. Article and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.4137606.

  • 3 These two authors contributed equally to this work.

  • 4 Present address: Tel Aviv University, Department of Human Genet-ics, Sackler Faculty of Medicine, Tel Aviv, 69978 Israel.

  • 5 Corresponding author. E-mail sorek{at}post.tau.ac.il; fax 972-3-7658555.

    • Accepted September 13, 2005.
    • Received May 16, 2005.

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