New research challenges understanding of human genome
Results from a huge international effort to identify the functional components of the human genome are challenging established views about how the genome works. Among other things, the concept of 'junk' DNA looks set to be binned, as the findings reveal that most of the genome has a function of some kind. The research is published in the journal Nature, with 28 companion papers appearing in the journal Genome. Part of the funding for the initiative came from the EU's Sixth Framework Programme through the BioSapiens Network of Excellence. The work was carried out within the framework of the ENCODE (Encyclopedia of DNA Elements) project, which has spent the past four years identifying and cataloguing the functional elements of 1% of the human genome. The human genome was sequenced in April 2003. Together, the three billion base pairs ('letters') of the genome contain all the information needed to turn a fertilised egg cell into an adult human being. While we have some understanding of the parts of the genome that code for proteins, the function of the rest of the genome remains a mystery. 'The problem is it is written in a language we are still trying to learn to understand,' said Francis Collins, Director of the US' National Human Genome Research Institute (NHGRI). The goal of the ENCODE project is to investigate the genome to find out what it is doing and why. In this initial pilot phase, 30,000 base pairs, equivalent to 1% of the total genome, were targeted. Half of these were in regions of the genome which are relatively well characterised, and the other half were picked at random. Scientists from 80 organisations in 11 countries and representing a range of disciplines ran a battery of tests on the target DNA sequences, sharing information, technology and data along the way. The result was over 200 datasets and over 600 million data points. 'This was a prime example of team science at its best,' commented Dr Collins. 'None of this data would have been as rich without this sharing.' 'Our results reveal important principles about the organisation of functional elements in the human genome, providing new perspectives on everything from DNA transcription to mammalian evolution,' said Ewan Birney of the European Molecular Biology Laboratory, who led the data analysis work. 'In particular, we gained significant insight into DNA sequences that do not encode proteins, which we knew very little about before.' One of the most exciting findings was the fact that most of the DNA in our cells is active in some way, challenging the idea that the genome consists of active protein-coding genes surrounded by vast amounts of inactive, so-called 'junk' DNA. Furthermore, many of these non-protein coding sequences overlap with protein-coding sequences. 'The junk is not junk. It is active. It does a lot of different things,' said Dr Birney. Many of the regions which were once thought to be junk have turned out to be regulatory sequences, which tell genes when and where they should be active. This finding will have implications for medicine, as many genetic mutations associated with diseases are found in regulatory regions. Another surprise for the scientists was the identification of 'neutral' sequences, which are being actively copied but provide neither a benefit nor a problem to the organism. These neutral sequences have not been conserved during evolution. The researchers speculate that these could be a source for new genetic variation in the future. 'It's like clutter in the attic,' explained Dr Collins. 'You wouldn't throw it away because you might need it.' One of the goals of the project was to develop the tools to carry out the analysis and ensure the feasibility of the project concept, which involved developing standards so that data from different laboratories and different experimental processes could be compared properly. 'We are now in a position to scale this up!' said Dr Collins. 'We are prepared to go from 1% to the whole thing.' 'The goal for the next five years is delivering a more complete understanding across our genome,' added Dr Birney. 'The ENCODE pilot project is the first step towards this goal.'
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