YORKTOWN HEIGHTS, N.Y.—Scientists at IBM Research announced recently the discovery of conserved sequence patterns within the human genome that suggest biological functions for DNA previously thought to represent dead areas between genes—the so-called junk DNA. As they reported in the Proceedings of the National Academy of Sciences, these sequences may provide novel insights into gene expression and biological processes, offering new clues to human disease.
"Our goal is to apply advanced computational techniques to analyze the workings of processes and systems, in this case the function of the human genome," explains Ajay Royyuru, head of the Computational Biology Center at IBM Research. "Using these tools, we've been able to shed new light on parts of the DNA that were traditionally thought of as not having a specific purpose. We believe the innovative application of technology can provide further understanding in the life sciences at large."
Using high-performance computing and pattern-recognition algorithms, the researchers identified almost 128,000 DNA sequence motifs that occurred more often than would be expected by chance. They termed these motifs pyknons and suggested that the sequences might provide some level of regulatory control at the RNA stage of gene expression.
Dr. Isidore Rigoutsos, manager of the bioinformatics and pattern discovery group at the IBM Thomas J. Watson Research Center, is quick to point out that pyknons may be related to but are distinct from microRNAs, which have been extensively studied in recent years.
"In terms of how pyknons are defined, namely their copy number and locations of their instances, they are distinct from microRNAs," he explains. "Having said this, it is important to note that at the sequence level, several hundred of the pyknons are very similar to known microRNA sequences. Moreover, for about 30 percent of the pyknons, their reverse complement is found inside intergenic/intronic neighborhoods with lengths and predicted secondary structure that are similar to those of typical microRNA precursors."
The researchers found that different pyknons clustered in patterns or mosaics around genes and that these patterns were often duplicated with slight variations in genes involved in specific biological processes, adding fuel to the speculation that the sequence motifs offer some degree of regulatory control. Rigoutsos remains cautious, however, about getting too far ahead of the data.
"If it is proven through experimental validation that the pyknons are indeed functional and serve a regulatory role, their discovery is likely to increase our understanding of transcript regulation and help us take a fresh look at the genetic causes behind at least some diseases," he says. "At the moment, the pyknons appear to suggest the existence of a very extensive regulatory layer that had escaped our attention for many years. However, and even though it is a very tantalizing possibility that such a layer may exist, it is more prudent to await experimental validation of the pyknons and of their regulatory role."
Given this caution, it is likely to be quite some time before the researchers' findings begin to make a difference in the drug discovery arena, but it is further indication of the increasing complexity and biological activity of the human genome. And perhaps further proof that one person's junk (DNA) is another person's biological treasure.