Genome projects turn functional

Over the last few years genome projects have decoded the DNA sequence of a number of different animals, including humans, mice, flies and worms. These reveal that a large number of genes are shared among all animals.

However, this sequence information does not reveal what the genes do to bring about the development and behaviour of the animal. This is the goal of functional genomics - to understand the function of every gene in the animal.

The new research was conducted by Dr Julie Ahringer and her team from the Wellcome Trust/Cancer Research UK Institute of Cancer and Developmental Biology at the University of Cambridge. Their research focused on the Nobel prize winning worm Caenorhabtidis elegans. (Sydney Brenner, H Robert Horvitz and John Sulston were awarded the 2002 Nobel prize in Physiology or Medecine for pioneering work on C. elegans).

Traditionally analyses of gene function have been done by examining the development of animals where a gene has been mutated; a very laborious process that is not feasible on a global scale. A rapid alternative is to use the technique called RNA interference (RNAi), which can transiently inactivate a gene's function so that the consequence can be examined.

The Caenorhabditis elegans worm has about 19,000 genes (humans have around 30,000). Using RNAi, Dr Ahringer's group inactivated, one by one, 86 per cent (16,757) of them. From the mutant phenotypes seen, they could assign a function for 1722 (10.3 per cent of those examined). Two-thirds of these functions were not previously known.

To carry out the RNAi technique, Dr Ahringer's group created a library of bacterial strains, one for each gene. RNAi is carried out by feeding the bacteria to the worms, causing inhibition of the gene in the worm and its offspring.

Now, any researcher can use this bacterial library to carry out new RNAi screens to study specific biological questions. For example, Dr Gary Ruvkun's group from MGH, Harvard (Ashrafi, et al.; Nature 16 January 2003) used the library to screen for genes involved in fat metabolism. They found 305 genes that reduce body fat stores and 112 that increase it; many of these genes have human counterparts not previously known to be involved in fat control. Thus this approach may well lead to new understanding of human fat metabolic disorders. Other studies have used the same RNAi library to study ageing, see Lee et al (2003) NatureGenetics and Dillin et al (2002) Science.

The new data and associated library will accelerate progress in understanding a wide range of biological processes, leading to insights into human gene function.