Bidirectional Gene Pairs in the Human Genome


Bidirectional gene pairs, also called head‐to‐head gene pairs, are defined as two genes on different strands with adjacent 5′‐ends. They are transcribed divergently in a variety of coordinated fashion. The region between a bidirectional gene pair is designated as a putative bidirectional promoter, which is suggested to coordinately regulate the expression of the pair. The closely located bidirectional gene pairs and their bidirectional promoters were recently found to be enriched in the human genome. Despite substantial interests in these gene pairs and their expression regulation through bidirectional promoters, their biological significance is not well understood. Furthermore, it is of particular interest to know when and how the bidirectional gene arrangement evolved. Here the current understanding of these pairs is reviewed: bidirectional gene pairs may have great biological significance, and the bidirectional gene arrangement has evolved during the evolution of vertebrates leading to mammals by relocation of existing genes.

Key Concepts:

  • Closely located bidirectional gene pairs are enriched in the human genome.

  • Bidirectional gene pairs show correlated expression pattern.

  • Bidirectional gene pairs tend to have basic function in cells such as DNA repair.

  • Bidirectional promoters lack TATA boxes and are enriched in CpG islands.

  • Specific transcription factors are overrepresented in bidirectional promoters.

  • Bidirectional genes pairs tend to transcribe actively.

  • Bidirectional gene arrangement has evolved during the evolution of vertebrates leading to mammals by relocation of existing genes.

  • Detailed mechanisms of bidirectional transcription and the evolutionary forces that shaped the bidirectional arrangement in the human genome remain to be elucidated.

Keywords: genome organisation; coexpression; promoter; neighbouring gene pair; genome evolution

Figure 1.

Organisation of neighbouring gene pairs. Three possible patterns are shown. Lines represent the genome sequence and arrows indicate the directions of the transcription of the genes.

Figure 2.

Size distribution of intergenic regions in vertebrates. Distribution of intergenic distances among HH (← →), TT (→ ←) and HT (→→) gene pairs for selected organisms is shown. Data are from Davila Lopez et al. . © Creative Commons Attribution License.

Figure 3.

Conservation of the human bidirectional gene pairs (<1 kb apart) in other eukaryotic genomes. The number of human pairs corresponding to the homologous pairs in the genomes of other species is shown. White bars represent the total number of homologous pairs in the genomes of other species. Black bars represent the homologous pairs that are adjacent in a bidirectional arrangement on the chromosome of other species. Modified from Koyanagi et al. . © Elsevier.

Figure 4.

Distribution of the homologues for the human bidirectional gene pairs (<1 kb apart) and for all the genes. The ‘crown group’ refers to the kingdom to which the species belongs (animalia, plantae and fungi). Modified from Koyanagi et al. . © Elsevier.



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Koyanagi, Kanako O, Imanishi, Tadashi, and Gojobori, Takashi(Dec 2013) Bidirectional Gene Pairs in the Human Genome. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0020776.pub2]