GENES are not scattered randomly across our genome, as we thought. Instead, they fall into a pattern of clusters, a discovery that could one day help biologists perform gene therapy more accurately.
Evolutionary biologists generally consider that natural selection ensures that whole organisms are designed as well as they could be. Yet the human genome is widely thought to be a second-rate design, because only around 2 per cent of its 3 billion 鈥渓etters鈥� code for proteins, while much of the rest appears to be functionless, repetitive junk.
Biologists have also assumed that genes are inserted at random positions in genomes, says Laurence Hurst, an evolutionary biologist at the University of Bath in the UK. But some chromosome regions have 20 or 30 times the concentration of genes that others have. And until now, it wasn鈥檛 clear why.
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Using a data set of over 10,000 genes, Hurst and his team have shown that genes expressed in a broad range of tissues are clustered in regions of the genome that are rich in guanine (G) and cytosine (C) 鈥� two of the four letters that make up the genetic code. These include genes that code for proteins such as transcription enzymes, which in turn help decode the rest of the genome. Genes expressed only in specific tissues tend to lie in areas of the genome rich in adenine (A) and thymine (T). One such example is epithelial mitogen, a gene expressed only in the tongue.
Researchers had already suspected that genes are clustered according to their pattern of expression, but the work of Hurst鈥檚 team is the largest analysis to confirm the pattern.
One possible explanation, says Hurst, is that a high GC content favours gene expression (Human Molecular Genetics, vol 12, p 2411). DNA rich in guanine and cytosine appears to be less rigid than DNA rich in adenine and thymine, and this may give transcription enzymes better access to the genome. Organisms in which chromosomal rearrangement places the genes for these enzymes in GC-rich regions would therefore be strongly favoured by natural selection.
Understanding the evolutionary benefits of certain genes being in certain stretches of DNA could help doctors attempting gene therapy, where the idea is to correct genetic diseases by inserting a working copy of a defective gene. Knowing whether a gene is better placed within GC or AT-rich stretches of the genome could increase the chances that the new gene will work as intended.
But Jakob Reiser, a gene therapy researcher at Louisiana State University in New Orleans, points out that getting a vector to deliver the gene to a prescribed place in the genome is still extremely difficult, a problem which needs to be overcome before researchers can exploit any hidden patterns.
