One surprising finding from the Human Genome Project was that our genome is of a relatively modest size compared to some lowly organisms (e.g. the marbled lungfish and the amoeba Polychaos dubium have genomes 40-200 times the size of ours).  How is it that we can make do with a fraction of the genes of these more simple species?  We are important after all!

Driven by gene envy, scientists the world over have tried to figure out just how we can generate sufficient complexity from such a (ahem) puny genome.

Canada to the rescue!  The results of a pivotal research study that sheds light on this puzzle has recently been published in Nature.  The work was conducted at the University of Toronto by a team led by Ben Blencowe and Brendan Frey.

The research shows the presence of a second genetic code – the splicing code – that governs in a tissue-specific manner how genes are processed to generate the complexity the organism requires.  By combining coding sequences in different ways the human genome is able to generate a much larger array of proteins than our ~23,000 genes would indicate.

All biologists know the mantra “Phenotype = Genotype + Environment” but few would have guessed the degree of interplay between our gene expression profiles and environmental cues.  The U of T study underlines the active dialog between our genes and the tissues they reside in.  Change the environment for a cell and you’ll see different gene splicing patterns and, ultimately, altered cellular behavior.

The implications of this work are profound.  For one, it makes you wonder how truly informative in vitro studies are since those cells are residing in a highly artificial environment lacking many of the tissue-specific cues they would encounter in the body.  Are in vitro gene expression patterns a faithful representation of what happens in the body?

In addition, alternative spicing patterns vary greatly between species (e.g. only 20% conserved between humans and mice) which casts doubt upon how much we can extrapolate from gene expression studies in rodent models.

One thing is for sure, the U of T study has changed the way we look at the function of the genome.  There is sure to be a torrent of research activity developing from this pioneering work which should shed further light on how our body talks to our genes.

John McCulloch

John provides assistance to life sciences entrepreneurs in business strategy, management, intellectual property, financing and licensing. See more…