Pilot of the Encyclopedia of DNA Elements Released Today
13 Jun, 2007 07:00 pm
After scientists revealed the map of the entire human genome in 2001, the ENCyclopedia Of DNA Elements (ENCODE) project was launched in September 2003 with the aim of identifying all the functional elements in the human genome sequence. The results of the pilot phase which focused on 1% of the human genome sequence are published this week in Nature (today on Nature online). Ewan Birney, head of genome annotation at the European Molecular Biology Laboratory?s European Bioinformatics Institute (EMBL-EBI), who led ENCODE answers our questions.
We expected to learn that the genome was a very complicated thing, but because of the scientific experiments we learned quite a few different things. I will just pull up some of the highlights of the things we learned. One of them is that transcription, the process of converting DNA into RNA, is much more complicated than we thought. Previously we thought that genes were just quite a discrete unit across the genome, and now we see transcription occurring in many complex ways across the genome. Second thing, we discovered a lot of things about how regulation works in genes. There is a lot more regulatory elements than we previously knew about, and they interact with transcription in more complicated ways. And now the final thing to highlight is that the comparison of the evolutionary sequences, sequences that have been conserved in the evolution and its new functional vector were quite unexpected. There are many functional elements that are not conserved and that was unexpected. Many of these may be neutral: they are sort of passengers in evolution, theyíre neither critical to the organism to live nor can they make your organism die.
This study challenges the traditional view of our genetic blueprint as a tidy collection of independent genes...
Yes. This is an area of transcription where we find a lot more transcription happening in the regions between genes. Now, one thing we showed was that transcription, additional transcription, probably doesnít create new proteins. Transcripts are involved in a very complex network which exists in genes. Now itís quite interesting to speculate about what this transcript is doing. We donít really know and itís not clear what these new transcripts are doing as they join different genes from different places in the genome together. And so it links to a lot more questions about how regulation works and how the transcription interacts with the production of proteins in gene.
How can these results be used ?
There are many gene association studies in which there are new results which link genetic diseases to regions of the genome. Sometimes these linkages were well understood in genes. But sometimes these genetic associations link regions of the genome to diseases where previously we knew nothing. Now in many cases we have some further hints about what some of these things are doing. So it will be quite interesting to check that in the future.
This pilot phase is organized as an international consortium of scientists. How did you work all together?
With a lot of emails and a lot of phone calls and thatís quite hard when it goes all the way from Singapour to California. Email was our main way of working together. We had a very active mailing list. And then we would have weekly phone calls as well and depending on your time lag that would either be an easy phone call to attend or quite a hard phone call to attend.
The next step would be to decipher the whole genome. How will you proceed?
The ENCODE project will scale up to the whole genome and these draft proposals are in review at the moment at the National Institutes of Health in Washington DC. And so by the middle of this year we will know which the experiment will be scaled up to the entire genome.
How long do you expect it to take?
I suspect the first results of the genome are expected to happen relatively quickly as soon as perhaps next year but probably the full genome will take at least another five years. And even at the end of these five years, that will not be the end of working on how the genome functions. This is just a first step beyond knowing what the whole sequence is to know more about how the genome works.
Ewan Birney is a Senior Scientist at the European Bioinformatics Institute in Cambridge
Interview by Clementine Fullias
This week issue of Nature.