Tuesday, 3 February 2009

The Genome: Still an Enigma

The publication of the human genome was a groundbreaking scientific moment. Previously scientists found and isolated genes of interest and sequenced them afterwards. This left many genes hidden for a long time as they had not been noticed, the more obvious genetic disorders being easier to spot and associate a particular gene with. Sequencing the entire genome turned the process on its head. DNA contains strict codes indicating the start and end of protein coding sequences, and so by looking for these codes in the whole sequence the total number of genes and their precise location could be identified. For the first time scientists had a list of every single gene, and one by one were able to figure out their roles.

When the project was originally undertaken it took 12 years of work and $3 billion of US taxpayers money (Or $300 million for the privately funded alternative project). It was anticipated that once this project was complete, we would know everything there is to know about genetics and with it would come cures for many and possibly all diseases. That is still some way off, but progress is being made in gene therapy and the diagnosis of genetic diseases is now much easier. The cost of sequencing a human genome is now less than $500,000 and falling rapidly each year, it is now cheap enough to consider sequencing not just one, but a thousand human genomes to see the variations between them and the distribution of particular gene variants, as is the plan for the Personal Genome Project which aims to complete this by 2011.

Before the genome was sequenced, it was estimated that there must be around 100,000 genes, based on the size of our genetic material and the genes we already knew at the time. The results surprised everyone; 20,000 genes is closer to the real number. Also curious was the finding that less than 5% of the genome actually codes for proteins, vast stretches seeming to be nothing more than 'junk DNA'.

Many scientists maintained that it can't all be junk, because that much junk would actually hinder organisms, taking so much energy to replicate that they would be out competed by other organisms and fail to survive. Some blamed viruses, retroviruses specifically, as they infect by integrating their genes into your genome. When the infection is fought off, often those viral genes remain in a damaged non-functional form and if the right cells were infected, the genes will be passed on to your offspring. As much as 10% of your genome has been found to be made of such material, accumulated over many millions of years, much of it mutated into non-functional junk. But this still leaves 85% of the genome unexplained.

RNA is the intermediate molecule used to make protein from DNA. As I discussed previously, life evolved in an RNA world, where strands of RNA themselves carried out functions as well as encoding proteins. So it is perhaps unsurprising that a project at Harvard and MIT recently discovered a whole new class of genes, genes that do not encode proteins, they are simply the template for functional RNA. Small RNA molecules such as Micro RNA, around 22 nucleotides in length, have been known to have gene regulation functions for many years, but this new class of large RNA molecules are thousands of nucleotides long and there are thousands of them. Crucially, their sequences have been conserved through evolution, indicating they have important functions as yet unidentified. 1600 of these genes were found in the study but it is thought many more thousands are still hiding in plain sight.

We already had quite a job on our hands to understand the 20,000 genes we originally identified, now there is a whole new class to understand, which operates in a whole other way. This new class may go some way to explaining what some of that junk DNA is there for, but there is still lots the genome has left to teach us. Just because we don't know what it does doesn't mean it is useless, just a few hundred years ago the brain was considered largely useless because it didn't do anything as obvious as the heart, lungs or stomach does. However, that is the process of science; learning new things and adjusting current opinion accordingly.

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