Now we begin to understand how the genome works!

By Peter Dearden 06/09/2012 2


Peter K. Dearden

You might have seen the press coverage of the release of the ‘Encode’ data which significantly increases our understanding of the functions of the Human genome. I have spent some time trying to explain it to the public, usually through using very unhelpful metaphors.

I thought, just in case people were still confused ( or more confused), that I’d write something about it.

The Encode consortium takes in more than 400 geneticists from across the world who have just published 30 papers, in various leading journals, about the functional bits of the human genome. This all springs from the publication of the human genome sequence in 2002. That sequence was an enormous achievement, allowing us to see what the genome codes for. What that sequence couldn’t tell us, however, was how the genome works. The Encode consortium has put one foot on the ladder to determining that.

The genome is very complicated, but less complicated than its regulation. Genes are not always turned ‘on’, indeed different genes are ‘on’ in different cells and tissues, and make those cells and tissues different from one another. Embryogenesis can be thought of as a vast programme of events, that, in a coordinated fashion, turns on the correct genes at the correct time and place, and turns off genes that shouldn’t be on in that cell type. With 20,000 odd genes in your genome, all of which are expressed at multiple times in your life and in multiple tissues, you can see that controlling when a gene is on or off is not only very complex and difficult, but key to understanding many Human conditions, including cancer.

This is the problem the Encode consortium has aimed to address. Using many different techniques they have begun to identify the ‘control elements’ that regulate the activity of a gene. Just to make life difficult, it turns out that their are multiple layers and types of such control elements,all acting to ensure your genes behave nicely. The published papers include ones on transcription factor binding sites, non-coding RNA, DNA methylation, chromatin modifications and more and more (Nature has a great site if you want to explore the papers)

This breakthrough is built on three things.

Firstly; The Human genome sequence and the variation we are finding in human genomes as we sequence them.

Secondly; new and novel techniques, often pioneered by the modENCODE consortium, who have being doing the same work in model organisms like fruit flies and worms.

Thirdly, and I think most importantly, a group of scientists, working across disciplines and national borders to address this massive problem.

I firmly believe that this approach is the future of modern biology, crowd-sourcing knowledge and expertise to help your own work, but also to ensure your work is contributing to the biggest problems that biology can provide. I long for the day my more traditional colleagues wake up to the fact that the paradigm of modern biology is changing, and open collaboration is the key.

Enough ranting. Mark the 6th of September 2012 as a big day in Genetics. My congratulations to ENCODERs around the world.

– for those of you who want a metaphor, it’s like the human genome is like a piano, and ENCODE has just found a book of music. Or, the human genome is like a Christmas pudding and the genes are the raisins…  Nope…


2 Responses to “Now we begin to understand how the genome works!”

  • What if a normal cell becomes cancerous by de-differentiation?

    And the code that gives us inherited characterists also contains the code for cell differentiation?

    As cells differentiate into mature tissues only one specific set of genes stays switched on in each kind.

    But what has become locked-up can be unlocked. The entire genetic blueprint is still carried in every cell nucleus.

    This is the essence of regeneration.

  • Yes cells can de-differentiate, but not often, and in many cases we are beginning to understand that cancers often have their own stem cells- suggesting that they may not be de-differentiated cells, but a rogue stem cell population.

    In regeneration too, often what is providing cells for regeneration are adult stem cells, kept in niches until needed.

    Even more weirdly, in some cases, such as regeneration of the Zebrafish heart, it seems that terminally differentiated cells divide to regenerate, with evidence for cellular reorganisation, but perhaps not de-differentiation.

    I think that this implies de-differentation is hard to do, and so is rare.