The human Genome Project has stimulated numerous new avenues for research, not the least of which relates to the functionality of the genome that does not code for proteins. Often referred to as "Junk DNA", this genetic material has previously had a tough time getting taken seriously. But not now. There are many signs of functionality. This is one aspect of the background to some newly published research.
"How much of the rest performs other biological functions, and how much is merely residue of prior genetic events? Scientists from Cold Spring Harbor Laboratory (CSHL) and the University of Chicago now report that 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."
"Previous researchers assumed that mutations in the middle of introns do not affect the final protein, so they simply accumulate." To assess the evidence for selection, the researchers looked in the genomes of humans and mice for symmetry and repeat patterns in specific code sequences.
"To test for conservation, researchers need to find matching stretches in the two species. This is relatively easy for stretches that "code" for proteins, where scientists long ago learned the meaning of the sequence. For "noncoding" regions, however, the comparison is often ambiguous. 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."
[. . .]
"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."
Without getting into details, this finding is potentially of great importance. Introns comprise about 30% of the genome, and the fingerprint of functionality is pervasive. The rest of the genome awaits further research, and we may find that most of that has some functionality also. We still have a lot to find out about how the splicing-regulatory elements work, and we can predict some interesting tests of contrasting hypotheses. The evolutionary hypothesis appears to be that Junk DNA has been coopted for the purposes of regulation, and can be described in terms of "tinkering evolution". The design hypothsis says nothing directly about the way the DNA code was assembled, but the prediction is of "exquisite design" features.
It is worth drawing attention to a blog by Cornelius Hunter which points out the gratuitous link with evolutionary theory in the various reports of this research:
"The paper's title alone ("RNA landscape of evolution for optimal exon and intron discrimination") suggests a new finding about evolution, and the paper concludes that human genes seem to have been optimized "during evolution." But the "during evolution" part is gratuitous. The key findings are about how the genetic signals work, not that they evolved. There is, in fact, nothing in the findings to indicate evolution. The science writer concluded that "the researchers found signs that evolution rejects some types of mutations," but there simply was no such finding. What the researchers actually found was the presence of certain subtle signals in the genome. They found no evidence that the signals were produced by evolution."
RNA landscape of evolution for optimal exon and intron discrimination
Chaolin Zhang, Wen-Hsiung Li, Adrian R. Krainer, and Michael Q. Zhang
Proc. Natl. Acad. Sci. USA, April 15 2008, 105(15, 5797-5802 | doi 10.1073/pnas.0801692105
Abstract: Accurate pre-mRNA splicing requires primary splicing signals, including the splice sites, a polypyrimidine tract, and a branch site, other splicing-regulatory elements (SREs). The SREs include exonic splicing enhancers (ESEs), exonic splicing silencers (ESSs), intronic splicing enhancers (ISEs), and intronic splicing silencers (ISSs), which are typically located near the splice sites. However, it is unclear to what extent splicing-driven selective pressure constrains exonic and intronic sequences, especially those distant from the splice sites. Here, we studied the distribution of SREs in human genes in terms of DNA strand-asymmetry patterns. Under a neutral evolution model, each mononucleotide or oligonucleotide should have a symmetric (Chargaff's second parity rule), or weakly asymmetric yet uniform, distribution throughout a pre-mRNA transcript. However, we found that large sets of unbiased, experimentally determined SREs show a distinct strand-asymmetry pattern that is inconsistent with the neutral evolution model, and reflects their functional roles in splicing. ESEs are selected in exons and depleted in introns and vice versa for ESSs. Surprisingly, this trend extends into deep intronic sequences, accounting for one third of the genome. Selection is detectable even at the mononucleotide level, so that the asymmetric base compositions of exons and introns are predictive of ESEs and ESSs. We developed a method that effectively predicts SREs based on strand asymmetry, expanding the current catalog of SREs. Our results suggest that human genes have been optimized for exon and intron discrimination through an RNA landscape shaped during evolution.
Scientists Find a Fingerprint of Evolution Across the Human Genome, Cold Spring Harbor, NY. Press Release, 8 April 2008
Hunter, C. Raising the Bar on the Evolution Debate, Evolution News & Views, 15 April 2008
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