The importance of being a highly conserved non-coding region

Yesterday Gill Bejerano (Stanford University) gave a talk at the PRBB in which he advocated the key role of highly conserved non-coding regions, in particular in the context of evolution.

He explained there are only about 20,000 human genes, but more than 1,000,000 genome ‘switches’, short DNA regions which control which genes are expressed and at what levels. And the so-called ‘gene deserts’, areas of the genome with very few genes in them, are actually very rich in these conserved non-coding elements which act as cis-regulators of gene expression. So, as he said, perhaps more than gene deserts they should be called ‘regulatory jungles’.

Just because of the sheer number of these regulatory units, their importance should not be overlooked – if there are so many they must be doing something. And their key role in gene regulation is more obvious each day.

But in the context of evolution and the apparition of new, beneficial mutations, their role takes a new dimension I, for one, hadn’t thought much about. Let me use Bejerano’s example, the Sall1 gene, a key gene during development that is expressed in limb, brain and neural tube. There are three enhancers for this gene, one for each of these locations. If a mutation appears in the gene itself, it will cause problems in all the regions the gene is expressed and therefore that mutation might be lethal and won’t be successful (evolutionary speaking). But if the mutation affects only one of the enhancers, it would have an effect just on one of the regions where the gene is expressed. Such a mutation would have more chances to be passed on to the next generation.  Therefore, beneficial mutations are more likely to appear in enhancers (highly conserved non-coding regions) than in genes. Enhancers would then play an essential role in evolution.

Report by Maruxa Martinez, Scientific Editor at the PRBB


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