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Functional & Integrative Genomics

, Volume 12, Issue 1, pp 45–61 | Cite as

Novel mechanism of conjoined gene formation in the human genome

  • Ryong Nam Kim
  • Aeri Kim
  • Sang-Haeng Choi
  • Dae-Soo Kim
  • Seong-Hyeuk Nam
  • Dae-Won Kim
  • Dong-Wook Kim
  • Aram Kang
  • Min-Young Kim
  • Kun-Hyang Park
  • Byoung-Ha Yoon
  • Kang Seon Lee
  • Hong-Seog ParkEmail author
Original Paper

Abstract

Recently, conjoined genes (CGs) have emerged as important genetic factors necessary for understanding the human genome. However, their formation mechanism and precise structures have remained mysterious. Based on a detailed structural analysis of 57 human CG transcript variants (CGTVs, discovered in this study) and all (833) known CGs in the human genome, we discovered that the poly(A) signal site from the upstream parent gene region is completely removed via the skipping or truncation of the final exon; consequently, CG transcription is terminated at the poly(A) signal site of the downstream parent gene. This result led us to propose a novel mechanism of CG formation: the complete removal of the poly(A) signal site from the upstream parent gene is a prerequisite for the CG transcriptional machinery to continue transcribing uninterrupted into the intergenic region and downstream parent gene. The removal of the poly(A) signal sequence from the upstream gene region appears to be caused by a deletion or truncation mutation in the human genome rather than post-transcriptional trans-splicing events. With respect to the characteristics of CG sequence structures, we found that intergenic regions are hot spots for novel exon creation during CGTV formation and that exons farther from the intergenic regions are more highly conserved in the CGTVs. Interestingly, many novel exons newly created within the intergenic and intragenic regions originated from transposable element sequences. Additionally, the CGTVs showed tumor tissue-biased expression. In conclusion, our study provides novel insights into the CG formation mechanism and expands the present concepts of the genetic structural landscape, gene regulation, and gene formation mechanisms in the human genome.

Keywords

Conjoined genes Formation mechanism Precise structures CGTVs Human genome 

Notes

Acknowledgements

We thank the members of the Genome Resource Center (GRC) in the Korea Research Institute of Bioscience and Biotechnology (KRIBB) for their active assistance in conducting this research project. This research was supported by grant 2009-0084206 from the Ministry of Education, Science and Technology (MEST) and grant KGM5411011 from KRIBB.

Competing financial interests

The authors declare no competing financial interests.

Supplementary material

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Ryong Nam Kim
    • 1
  • Aeri Kim
    • 1
    • 2
  • Sang-Haeng Choi
    • 1
  • Dae-Soo Kim
    • 1
  • Seong-Hyeuk Nam
    • 1
  • Dae-Won Kim
    • 1
  • Dong-Wook Kim
    • 1
  • Aram Kang
    • 1
    • 2
  • Min-Young Kim
    • 1
  • Kun-Hyang Park
    • 1
  • Byoung-Ha Yoon
    • 1
    • 2
  • Kang Seon Lee
    • 1
  • Hong-Seog Park
    • 1
    • 2
    Email author
  1. 1.Genome Resource CenterKorea Research Institute of Bioscience and Biotechnology (KRIBB)DaejeonSouth Korea
  2. 2.University of Science and Technology (UST)DaejeonSouth Korea

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