Orthology-driven mapping of bidirectional promoters in human and mouse genomes

The presence of bidirectional promoters in all vertebrate species suggests that the promoters may be maintained in orthologous positions. Therefore the identification of the comprehensive orthologous mapping of this type promoter across species can facilitate elucidation of regulatory mechanisms controlling bidirectional gene expression. However, the lack of annotation for many transcribed regions in the genome can impact the orthology designation of these promoters. Human and mouse are among genomes that have been relatively well annotated. Thus we used them as models to study the orthologous patterns of bidirectional promoters.

We developed a method to annotate these regulatory regions by confirming the orthology of the genes found on each side of the promoters. In this manuscript we report the cross-species comparisons between human and mouse genomes, where the bidirectional promoter sets regulating UCSC Known Genes and spliced EST annotations were mapped from human to mouse and vice versa. We validate hundreds of orthologous bidirectional promoters through the presence of orthologous flanking gene annotations in the second species. We also show that regulatory activity of these orthologous promoters confers similar gene expression profiles in 21 tissues of human and mouse. In particular, more than one third of human bidirectional promoters annotated from spliced EST annotations regulate ncRNA, of which over 90% are lncRNAs.

Although evolutionary conservation shows a weaker signature in promoters than coding regions, our technique of mapping of orthologous genes shows that most bidirectional promoter arrangements are conserved across human and mouse genomes, suggesting a critical function. In addition, the similar expression patterns of the orthologous gene sets indicate that the regulatory mechanisms remain largely conserved as well.