The adjacent positioning of co-regulated gene pairs is widely conserved across eukaryotes

Abstract

BackgroundCoordinated cell growth and development requires that cells regulate the expression of large sets of genes in an appropriate manner, and one of the most complex and metabolically demanding pathways that cells must manage is that of ribosome biogenesis. Ribosome biosynthesis depends upon the activity of hundreds of gene products, and it is subject to extensive regulation in response to changing cellular conditions. We previously described an unusual property of the genes that are involved in ribosome biogenesis in yeast; a significant fraction of the genes exist on the chromosomes as immediately adjacent gene pairs. The incidence of gene pairing can be as high as 24% in some species, and the gene pairs are found in all of the possible tandem, divergent, and convergent orientations.ResultsWe investigated co-regulated gene sets in S. cerevisiae beyond those related to ribosome biogenesis, and found that a number of these regulons, including those involved in DNA metabolism, heat shock, and the response to cellular stressors were also significantly enriched for adjacent gene pairs. We found that as a whole, adjacent gene pairs were more tightly co-regulated than unpaired genes, and that the specific gene pairing relationships that were most widely conserved across divergent fungal lineages were correlated with those genes that exhibited the highest levels of transcription. Finally, we investigated the gene positions of ribosome related genes across a widely divergent set of eukaryotes, and found a significant level of adjacent gene pairing well beyond yeast species.ConclusionWhile it has long been understood that there are connections between genomic organization and transcriptional regulation, this study reveals that the strategy of organizing genes from related, co-regulated pathways into pairs of immediately adjacent genes is widespread, evolutionarily conserved, and functionally significant.

Juxtaposed genes in 7q21‐22 amplicon contribute for two major gastric cancer sub‐Types by mutual exclusive expression

“…Adjacent genes of genomic loci are often expressed together . This study highlights the occurrence of multiple genes in a defined genomic region often amplified in gastric tumors and cell lines.…”

Dissecting the cis and trans Elements That Regulate Adjacent-Gene Coregulation in Saccharomyces cerevisiae

“…When we first identified and characterized the membership of the RRB regulon, we noticed that a significant fraction (roughly 15%) of the RRB genes were located on the chromosomes as immediate, adjacent gene pairs. Significant levels of adjacent-gene pairing were subsequently found in other coregulated gene sets in budding yeast and in the RRB and RP regulons across divergent eukaryotes (22). Additionally, the sets of paired genes were found to be more tightly coregulated across multiple changing growth conditions than were those of the unpaired genes of the same regulons.…”

“…A significant fraction of the RP and RRB genes exist as immediately adjacent gene pairs, and this arrangement results in a tighter transcriptional coordination than those of genes within the same regulons that are not paired (10,22). This phenomenon of adjacent-gene pairing extends to other large coregulated gene sets, including those related to DNA damage response, carbohydrate metabolism, nitrogen metabolism, and heat shock response (22).…”

“…A significant fraction of the RP and RRB genes exist as immediately adjacent gene pairs, and this arrangement results in a tighter transcriptional coordination than those of genes within the same regulons that are not paired (10,22). This phenomenon of adjacent-gene pairing extends to other large coregulated gene sets, including those related to DNA damage response, carbohydrate metabolism, nitrogen metabolism, and heat shock response (22). Importantly, more than half of the adjacent gene pairs are found in tandem or convergent orientations, suggesting that their coregulation is not simply a consequence of bidirectional promoters, like that described for the GAL1-GAL10 genes (23).…”

Two by Two: Co-Regulating Adjacent Gene Pairs in Yeast and Beyond

“…Significant gene pairing can be seen across numerous functional pathways in S. cerevisiae including the Gene Ontology (GO) groupings for DNA damage response (16/175 genes), carbohydrate metabolism (9/91 genes), nitrogen metabolism (8/86 genes), heat shock response (4/18 genes) and more. Furthermore, the paired members of the respective gene sets tended to represent those genes that were the most highly expressed, and they were more likely to remain as paired genes across divergent yeasts when compared to random pairings [9]. There is even evidence that elevated levels of RP gene pairing exists across other eukaryotes, including in C. elegans, and D. melanogaster (Table 1).…”