Ridges (regions of increased gene expression) are domains of the genome with a high gene expression; the opposite of ridges are antiridges. The term was first used by Caron et al. in 2001. Characteristics of ridges are: Gene dense Contain many C and G nucleobases Genes have short introns High SINE repeat density Low LINE repeat density
Discovery
Clustering of genes in prokaryotes was known for a long time. Their genes are grouped in operons, genes within operons share a common promoter unit. These genes are mostly functionally related. The genome of prokaryotes is relatively very simple and compact. In eukaryotes the genome is huge and only a small amount of it are functionally genes, furthermore the genes are not arranged in operons. Except for nematodes and trypanosomes; although their operons are different from the prokaryotic operons. In eukaryotes each gene has a transcription regulation site of its own. Therefore, genes don't have to be in close proximity to be co-expressed. Therefore, it was long assumed that eukaryotic genes were randomly distributed across the genome due to the high rate of chromosome rearrangements. But because the complete sequence of genomes became available it became possible to absolutely locate a gene and measure its distance to other genes.
The first eukaryote genome ever sequenced was that of Saccharomyces cerevisiae, or budding yeast, in 1996. Half a year after that Velculescu et al. (1997) published a research in which they had integrated SAGE data with the now available genome map. During a cell cycle different genes are active in a cell. Therefore, they used SAGE data from three moments of the cell cycle (log phase, S phase-arrested and G2/M-phase arrested cells). Because in yeast all genes have a promoter unit of their own it was not suspected that genes would cluster near to each other but they did. Clusters were present on all 16 yeast chromosomes. A year later Cho et al. also reported (although in more detail) that certain genes are located near to each other in yeast.
Characteristics and function
Co-expression
Cho et al. were the first who determined that clustered genes have the same expression levels. They identified transcripts that show cell-cycle dependent periodicity. Of those genes 25% was located in close proximity to other genes which were transcript in the same cell cycle. Cohen et al. (2000) also identified clusters of co-expressed genes.
Caron et al. (2001) made a human transcriptome map of 12 different tissues (cancer cells) and concluded that genes are not randomly distributed across the chromosomes. Instead, genes tend to cluster in groups of sometimes 39 genes in close proximity. Clusters were not only gene dense. They identified 27 clusters of genes with very high expression levels and called them RIDGEs. A common RIDGE counts 6 to 30 genes per centiray. However, there were great exceptions, 40 to 50% of the RIDGEs were not that gene dense; just like in yeast these RIDGEs were located in the telomere regions.
Lercher et al. (2002) pointed to some weaknesses in Caron's approach. Clusters of genes in close proximity and high transcription levels can easily been generated by tandem duplicates. Genes can generate duplicates of themselves which are incorporated in their neighborhood. These duplicates can either became a functional part of the pathway of their parent gene, or (because they are no longer favored by natural selection) gain deleterious mutations and turn into pseudogenes. Because these duplicates are false positives in the search for gene clusters they have to be excluded. Lercher excluded neighboring genes with high resemblance to each other, after that he searched with a sliding window for regions with 15 neighboring genes.
It was clear that gene dense regions existed. There was a striking correlation between gene density and a high CG content. Some clusters indeed had high expression levels. But most of the highly expressed regions consisted of housekeeping genes; genes that are highly expressed in all tissues because they code for basal mechanisms. Only a minority of the clusters contained genes that were restricted to specific tissues.