ONCE, it all seemed so beautifully simple. Our DNA, we thought, consisted of a set of recipes, or genes, for making proteins, and once we had identified them all and worked out what they do, we would be a long way towards understanding what makes us what we are.
If only. One of the big shocks that emerged from the human genome project was that we have 鈥� barely more than a nematode worm. But in many other ways our genome is turning out to be dizzyingly complex (see diagram).
鈥淚t is very difficult to wrap your head around how big the genome is and how complicated,鈥� says of the European Bioinformatics Institute near Cambridge, UK, who is part of to uncover the workings of the genome. 鈥淚t鈥檚 very confusing and intimidating.鈥�
Advertisement
For starters, rather than each gene coding for one protein, they often code for many. The coding parts of genes come in pieces, like beads on a string, and by splicing out different beads, or exons, after RNA copies are made, a single gene can potentially code for tens of thousands of different proteins, although the average is about five. Recent studies suggest in this way. Even more astonishingly, in at least one case in humans, RNA copies of different genes are spliced together. If this is commonplace, it would vastly multiply the potential number of different proteins.
Another recent discovery is that instead of having two copies of every gene 鈥� one from each parent 鈥� we often have just one or three or more. This 鈥�copy number variation鈥� is a result of big chunks of DNA being lost or duplicated, and could help to explain much of the normal variation between individuals, as well as diseases such as schizophrenia.
It鈥檚 the way in which genes are switched on and off, though, that has turned out to be really mind-boggling, with layer after layer of complexity emerging. Early studies suggested that gene activity was regulated mainly by transcription factors 鈥� proteins that bind to DNA, blocking or boosting the production of RNA copies of a gene and thus the amount of protein that gene produces.
While transcription factors do play a big role, cells also produce a wide variety of RNAs that, rather than coding for a protein, control gene activity. Some, dubbed small interfering RNAs (siRNAs), form complexes that seek out and destroy RNA copies of genes with a complementary sequence, preventing protein production. MicroRNAs work in a similar way but are not as specific, controlling the activity of many genes simultaneously. Piwi-acting RNAs, meanwhile, shut down the parasitic genes that litter our genome to stop them wreaking havoc, though it鈥檚 not clear how.
Nonintelligent design
The list of regulatory RNAs grows longer by the day. In some cases, though, it is the act of making RNA rather than the product that matters: producing an RNA copy of one DNA strand chemically alters the proteins around which DNA is wrapped, shutting down genes on the opposite strand.
Such convoluted mechanisms might seem odd and rather wasteful, but that is just what we should expect. 鈥淵ou sometimes ask yourself, 鈥榃hy on earth is biology working this way?鈥�,鈥� says Birney. 鈥淏ut from evolution鈥檚 perspective it doesn鈥檛 have to look good in a textbook, it just has to work.鈥�
Unfortunately, it only has to work in some of us. The Byzantine complexity and means there is an awful lot that can go wrong, and all too often it does, argues John Avise of the University of California, Irvine. Splicing mistakes and errant microRNAs play a role in some cancers, for instance. On the bright side, discoveries like siRNA could lead to potent new treatments for all kinds of diseases.
What鈥檚 certain is that there is much more to discover. 鈥淭he genome is the start, not the end of the process,鈥� says Birney.
Read more: Unknown genome: What we still don鈥檛 know about our DNA
