Wednesday, April 09, 2008

The Fingerprint of Evolution

RNA landscape of evolution for optimal exon and intron discrimination. 2008. C. Zhang et al. PNAS, to be published on-line, April 15
One of the steps in turning genetic information into proteins leaves ‘genetic fingerprints’, even on regions of the DNA that are not involved in coding for the final protein. They estimate that such fingerprints affect at least a third of the genome, suggesting that while most DNA does not code for proteins, much of it is nonetheless biologically important – important enough, that is, to persist during evolution.
To gauge how critical a particular stretch of DNA is, biologists often look at the detailed sequence of “letters” it consists of, and compare it with a corresponding stretch in related creatures like mice. If the stretch serves no purpose, the thinking goes, the two sequences will differ because of numerous mutations since the two species last shared an ancestor. In contrast, it’s believed that the sequences of important genes will be similar, or “conserved,” in different species, because animals with mutations in these genes did not survive. Biologists therefore regard conserved sequences as a sign of biological importance.

Even within a gene, stretches of DNA that code for pieces of the target protein are usually interspersed with much larger noncoding stretches, called introns, that are removed from the RNA working copy of the DNA before the protein is made.

Previous researchers assumed that mutations in the middle of introns do not affect the final protein, so they simply accumulate. In the new work, however, the researchers found signs that evolution rejects some types of mutations even in these regions of the genome. Although the selection is weak, “introns are not neutral,” in their effect on survival, says Michael Zhang.

The scientists found a preference for some “letters” across intron regions, and the opposite preference in coding regions. Together, these regions make up at least a third of the genome, which is thus under selective pressure during evolution. The result supports other recent studies that suggest that, although most DNA does not code for proteins, much of it is nonetheless biologically important.