Systematic Analysis of Head-to-head Gene Organization: Evolutionary Conservation and Potential Biological Relevance

Jmjd6, a JmjC Dioxygenase with Many Interaction Partners and Pleiotropic Functions

“…Jmjd6 and Mettl23 cluster in a ‘head-to-head’ transcriptional orientation in all vertebrates from humans to puffer fish (Hahn et al, 2008). Such ancestral conservation of head-to-head gene organization is often correlated with significant overlap of expression patterns and functional associations of the genes involved (Li et al, 2006; Gherman et al, 2009). Although the precise TSS do not overlap, both genes are widely expressed in mouse and human datasets in FANTOM5, and the two genes probably share transcriptional regulatory elements within the CpG island that overlaps the shared TSS region.…”

Divergent Transcription: A Driving Force for New Gene Origination?

“…The model could explain the origin of divergent protein-coding gene pairs separated by less than 1 kb (usually less), which account for 10% of human protein-coding genes (Adachi and Lieber, 2002; Li et al, 2006; Piontkivska et al, 2009; Trinklein et al, 2004; Wakano et al, 2012; Xu et al, 2012), far higher proportion than would be expected if genes were randomly distributed in the genome. The model proposed here provides a natural explanation for the evolutionary origin of these gene pairs.…”

“…The model also predicts that divergent gene pairs commonly have unrelated functions, although they frequently might share co-expression. Except for a few cases, such as histone gene pairs and collagen gene pairs that are likely results of tandem duplication, the majority of divergent gene pairs in the human genome do not share higher functional similarity compared to random gene pairs (Li et al, 2006; Xu et al, 2012). For example, 35 of the 105 annotated DNA repair genes have bidirectional promoters, making DNA repair the most over-represented pathway for genes involved in bidirectional promoters, yet all 35 DNA repair genes are paired with non-DNA repair genes (Xu et al, 2012).…”

“…For example, 35 of the 105 annotated DNA repair genes have bidirectional promoters, making DNA repair the most over-represented pathway for genes involved in bidirectional promoters, yet all 35 DNA repair genes are paired with non-DNA repair genes (Xu et al, 2012). Similarly, genes coding subunits of protein complexes are enriched in bidirectional pairs in human, yet none of these pairs code for two subunits of the same complex (Li et al, 2006). A similar observation has been reported for yeast and is consistent with the argument that the bidirectional conformation reduces expression noise and is not strongly selected for share functionality (Wang et al, 2011).…”

“…The correlation between transcription and translocation could potentially increase the chance that the translocated gene is still expressed and thus functional, therefore reducing the cost of translocation. For example, although ~40% of human protein coding genes can be traced back to fish, fewer than 7% (83/1262) of human bidirectional gene pairs are also bidirectional in the fish genome (Li et al, 2006), suggesting that most human bidirectional gene pairs formed with young genes, or by bringing together old genes through translocation facilitated by divergent transcription.…”