Major Paradigm Shift for our DNA

Philosophers of science love this sort of thing. They refer to it as a paradigm shift. Living through such a shift is confusing for the scientists involved, and this one is no exception. But when it is over, it is likely to have changed people's views about how cells regulate themselves, how life becomes more complex, how certain mysterious diseases develop and even how the process of evolution operates. As a bonus, it also opens up avenues to develop new drugs.

Genes were once thought of almost exclusively as repositories of information about how to build proteins. Now, they need to be seen for what they really are: RNA factories. Genes for proteins may even be in the minority. In a human, the number of different microRNAs, one of the commonest of the newly discovered sorts of RNA, may be as high as 37,000 according to Isidore Rigoutsos, IBM's genome-miner in chief. That compares with the 21,000 or so protein-encoding genes that people have

Other evidence suggests that microRNAs regulate the activity of at least a third of human protein-encoding genes. This means there are very few cellular processes that do not happen under their watch. Around 20 microRNAs, for instance, are made only in human embryonic stem cells. These molecules could turn out to be the key to understanding how such cells remain in a state from which they can become any other type of cell?the very reason embryonic stem cells hold such great medical promise.

The existence of microRNAs may also help to explain why some creatures are more complex than others. Until their discovery, this was something of a paradox. Knowing that DNA stores data that then get translated into living organisms, and that the complexities of development must require lots of information, biologists naturally expected that the more intricately formed an organism is, the more genes it would have in its cells. They therefore struggled when they found that C. elegans, a tiny worm that lacks a proper brain but is nevertheless widely studied by geneticists, has about 20,000 genes?only a little bit short of the number in a human. Indeed, this seems to be a general number for animals. Another geneticists' favourite, the fruit fly Drosophila, has a similar number. But, of course, the genes in question are protein-coding genes. Add in the genes whose RNA does other things and the balance changes.

It changes even more if exactly what those RNA molecules do is examined. Single microRNAs, for example, often regulate the levels of hundreds of different proteins. They are like powerful strings controlling copious protein puppets. Super-imposed on this, some types of regulatory RNA edit other kinds of RNA. The effect of extra genes for both of these sorts of RNA molecules is therefore multiplicative rather than additive.

The picture that is emerging is thus one of ?hard-wired? simple organisms, which mostly stick to using RNA for fetching and carrying, and ?soft-wired? complex ones that employ it in a management capacity. In the complexity stakes, it is not how many protein-coding genes you have, but how you regulate them, that counts.