We’ve learn a lot about DNA in the last 50 years. In the 21st century the double helix structure of DNA is so familiar to us it is even used as part of commercials for beauty products! But for all the knowledge we have gained, DNA has a considerable amount of mystery surrounding it. For example, while we know that about 2% of the human genome codes for proteins, the exact function of the non-coding DNA (the other 98%) isn’t exactly known. It is generally accepted this non-coding DNA is evolutionarily constrained because it is important to the organism, but we don’t really know what its function is, or how exactly this DNA affects the phenotype of the individual. Conventionally we would say the function of non-coding region is determined by their sequence, so most methods of comparing genomes (to determine evolutionary relationships) focus on the nucleotide sequence. An article published in Science this month however, points to clear evidence that the exact shape of the non-coding regions has been determined by evolution, and is thus as important to our genetic make-up as the sequence of nucleotides.
The study was essentially a comparison of the genomes of 36 different species. However, this study devised a new method of matching (‘Chai’) so that similarities in both sequence and structure could be identified. In normal sequence-based constraint algorithms, the probability of observed sequence similarities being ‘flukes’ are calculated; the ‘Chai’ computer program incorporates structural information into this algorithm. It was reasoned that any strong matches across the different species would imply the DNA section had been selected and preserved by evolution, and thus has some important biological function.
Overall, the study found 12% of the human genome matched other genomes by shape- double the number that matched the sequence of others. These structurally similar regions correlated better to known functional non-coding elements of genes (like transcription enhancers) than the regions just identified on the basis of their sequence.
Furthermore, the study identified that relationship between the structural profile of a DNA molecule and its nucleotide sequence is not overly simple. It was found that similar sequences of DNA can adopt similar structures or in some cases very different structures, and very different sequences can have very similar structures.
The conclusion of the report states that, “Our high-resolution topography-based constraint-detection method reveals that structure-informed constraint is widespread in the human genome, and that these regions overlap known non-coding functional sites. Because different DNA sequences can have similar local structures, these regions might escape detection with sequence-based conservation–identification methods.” So, in non-coding regions of DNA, the sequence of bases appears to be more important because of the shape it gives to the DNA, rather than any information coded within it. Although this doesn’t explain exactly how shape is functions in non-coding DNA regions, it identifies that the molecular shape of DNA is subject to selection and is therefore an important part of evolutionary history, and the process of better understanding DNA.
Original Article:
Parker, Stephen. C.J. 2009. “Local DNA Topography Correlates with Functional Noncoding Regions of the Human Genome”, Science, March 12, [Online], Available: http://www.sciencemag.org.ezproxy.library.uq.edu.au/cgi/content/abstract/sci;1169050v1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&fulltext=parker+shape+DNA+chai&searchid=1&FIRSTINDEX=0&resourcetype=HWCIT [2009, March 24]
Other References:
Ball, Phillip. 2009. “There's more to life than sequences”, Nature, March 12, [Online], Available: http://www.nature.com.ezproxy.library.uq.edu.au/news/2009/090312/full/news.2009.160.html [2009, March 24]
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