The power of symbols

As a biologist I consider myself a lucky one. Not only I witnessed a revolution, I even took part on it. During my years in the lab of Eric Davidson at Caltech, I have seen the transformation of Developmental Biology from the mess it was until the mid-late ‘90s into the logic-driven science of Gene Regulatory Networks. Now after more than six years, I see how the fruits of that community effort are still plentiful and juicy.

But other than that spark of well needed clarity, there is something else that came along with that reformation. That is the introduction of the little symbol you see at the beginning of this post, to identify a gene. Here, the horizontal line is DNA; the bent arrow is the gene’s transcriptional start site; right of it is the coding sequence; left of it the cis-regulatory region (CRR), that portion of the genomic DNA that determine where when and how much a gene will be transcribed in a cell. Put this little thingie (and its power of transforming regulatory information into transcriptional outputs) in the context of the genetic interactions that go in development and there you have drawn your Gene Regulatory Network. No wonder this powerful little symbol is enjoying an increasingly wide acceptance. However the reductionism(s) that it implies also deserve attention. For as long as the CRR is intact a gene will perform their job, no matter where it is placed in a genome, as two decades of experiments of transgenesis have shown. As a result, genomic location effects on gene activity are mostly absent from the horizon of mainstream developmental biology discussion. At best they are (sometimes) vaguely noted as “positional effects”. For all practical matters genomes are treated as mere “gene container”. I believe that a look at some of the most recent reports from genome projects will fully prove this point.

How can such a conception coexist with four decades of studies that show that genomes are ordered, structured places? Gene physical as well as functional properties conforms to those of the genomic region they belong. Therefore GC-rich genes are in GC-rich regions of the genomes and tend to be the more expressed ones. This and a number of other observations point to a conception of genomes as integrated systems; evolutionary forces shaping the whole genomic landscape, not just the genetic one.

So how exactly would the integration between genes and genomes be obtained? What is somewhat surprising (and disappointing) is that, as far as I am aware, there is not a serious attempt in the field to understand how the functionality of cis-regulatory regions might be affected by the properties of genomic context in which they are embedded. Incidentally, this is the starting point of my research programme at SZN. Though still in its infancy it is showing some promising results: genomic context can affect the function of genes in ways that can be measured and understood. Do genomic contexts also put a constrain on the evolution of cis-regulatory regions? Boh?

‘till next one

Gabriele Amore