Focus: Melting into Our Genes
Our genes are spelled out one by one in long twisting molecules of DNA, but each gene contains stretches of “junk DNA,” genetic gibberish that serves no obvious biological purpose. Now, computer studies show that many of these useless “introns” lie between chunks of gene that melt at slightly different temperatures. Reported in the 6 May PRL, the results suggest that thermodynamics, and not just the specific lettering of the genetic code determines where the introns appear in our genes. Biologists are skeptical, however.
Each gene spells out the chemical recipe for a specific protein, and introns pervade these instructions in humans and many other creatures. The cell’s biochemical machinery “transcribes” the gene into a molecule called RNA, chops out the mumbo jumbo from the transcribed introns, and then “translates” the cleaned-up RNA into protein. No one knows precisely how junk DNA has worked its way into the genetic code over millions of years of evolution, although introns tend to wedge themselves between certain sequences of a few “letters.”
But thermodynamics may play a key role, too, report physicists Enrico Carlon, Ralf Blossey, and Mehdi Lejard Malki of the Interdisciplinary Research Institute in Villeneuve d’Ascq, France, who used computer simulations to study the melting of DNA. Relying on well established models, the researchers studied the melting of 83 human genes. Instead of analyzing the genes as they are found naturally, they studied virtual DNA strands in which all the introns had been chopped out and the protein-producing stretches, or “exons,” had been linked together.
The DNA for a gene consists of two long strands, one containing the genetic code, and the other containing a mating sequence analogous to the negative of a photograph. As the temperature rises above 70 degrees Celsius and the molecule melts, the strands separate in fits and starts, with different stretches letting go at different temperatures. The stretches, or “melting domains,” that part at higher temperatures are more stable than the ones that split at lower temperatures, so melting temperature is a measure of stability. In their study, Carlon and colleagues found that the ends of the melting domains generally coincided with the ends of the exons.
The correlation between exons and melting domains suggests that junk DNA slips into genes at the ends of the melting domains in a process driven by thermodynamics, Carlon says. That might happen when the two strands partially separate to form a Y at the end of a less-stable domain and the beginning of a more stable one, like a partially unzipped zipper. A string of meaningless letters might somehow nestle into the Y and elbow its way between the exons when the molecule zips up again, the physicists speculate.
But the physicists’ interpretation of their findings raises several questions, biologists say. Within a given gene, introns fit into different places in different species, notes Nicholas Dibb of Imperial College London in the UK. So the correlations observed in human genes won’t hold in other organisms, Dibb says, unless their genes also melt in different places. John Logsdon of the University of Iowa in Iowa City notes that the exons themselves may have evolved into melting domains, as that might help the cell splice out the gibberish from the introns in the RNA. If so, the physicists have interpreted the relationship between melting domains and exons essentially backwards, Logsdon says: “The question is whether we have a cause or a correlation.”
Adrian Cho is a freelance science writer in Grosse Pointe Woods, Michigan.