Hurtling toward the RNA world—the idea that RNA evolved before DNA—is an alternative hypothesis, one that suggests that RNA and DNA evolved simultaneously and, for the most part, separately, at least at first. The alternative hypothesis doesn’t so much threaten to destroy the RNA world as to alter its trajectory. It may be that the RNA world and the DNA world once traversed a shared orbit.

Adding to the pull toward this new prebiotic constellation is a new finding: RNA/DNA hybrids would have been unstable. Such hybrids, chimeras with RNA/DNA backbones, have been proposed to explain how the RNA world could have progressed to a DNA world. Yet they have not been well studied. Presumably, they would have had many opportunities to arise, given the clutter of prebiotic chemistry. At the prebiotic or protobiological stage, sophisticated separation/discrimination mechanisms were lacking, and RNA/DNA chimeric sequences could have been common—common enough to establish a heterogeneous stage in chemical evolution.

Chimeric instability, however, argues against the idea of a heterogeneous stage that would have existed between a homogeneous RNA world and life’s chemistry as we know it, which consists of two homogeneous RNA and DNA systems. These systems interface with each other rather than give rise to hybrid species with RNA/DNA backbones.

Evidence of chimeric instability was uncovered by scientists based at The Scripps Research Institute (TSRI). These scientists, led by Ramanarayanan Krishnamurthy, Ph.D., published their findings September 21 in the journal Angewandte Chemie, in an article entitled “RNA–DNA Chimeras in the Context of an RNA World Transition to an RNA/DNA World.”

“We show that there is a significant decrease in Watson–Crick duplex stability of the heterogeneous backbone chimeric duplexes that would impede base-pair mediated interactions (and functions),” wrote the article’s authors. “These results point to the difficulties for the transition from one homogeneous system (RNA) to another (RNA/DNA) in an RNA world with a heterogeneous mixture of ribo- and deoxyribonucleotides and sequences, while suggesting an alternative scenario of prebiological accumulation and co-evolution of homogeneous systems (RNA and DNA).”

In other words, the new study shows a very deep drop in thermal stability when RNA and DNA share the same backbone. The chimeras do not stay together as well as pure RNA or pure DNA, which would compromise their ability to hold genetic information and replicate.

According to Dr. Krishnamurthy, who in addition to his position at TSRI has joint appointments with the NSF-NASA Center for Chemical Evolution and the Simons Collaboration on the Origins of Life, the instability discovered by his team appears to be due to a difference in the DNA sugar molecule structure versus the RNA sugar molecule. This new finding supports previous research from Nobel laureate and Harvard University chemistry and chemical biology professor Jack Szostak, who showed a loss of nucleotide-binding aptamer function when RNA mixed with DNA.

Because of this instability, chimeras in the RNA world would have likely died off in favor of more stable RNA molecules. This reflects what scientists see in cells today: If RNA nucleobases mistakenly join a DNA strand, sophisticated enzymes will rush to fix the mistake. Evolution has led to a system that favors more stable, “homogeneous” molecules.

These sophisticated enzymes were probably not around at the time of RNA's and DNA's early evolution, so these substitutions may have had a crippling effect on the molecules' ability to replicate and function. “The transition from RNA to DNA would not have been easy without mechanisms to keep them separate,” explained Dr. Krishnamurthy.

This realization led the scientists to consider an alternate theory: RNA and DNA may have arisen in tandem. “Even if you believe in a RNA-only world, you have to believe in something that existed with RNA to help it move forward,” argued Dr. Krishnamurthy. “Why not think of RNA and DNA rising together, rather than trying to convert RNA to DNA by means of some fantastic chemistry at a prebiotic stage?”

Dr. Krishnamurthy emphasized that his lab is not the first to propose this theory, but the findings on chimeric instability give scientists new evidence to consider. If the two evolved at the same time, DNA could have established its own homogeneous system early on. RNA could have still evolved to produce DNA, but that may have occurred after it first met DNA and got to “know” its raw materials.

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