Pre-RNA? Hybrids between proteins and nucleic acids may have helped genetic molecules evolve.


DNA-like Molecule Replicates Without Help

Researchers pondering the origin of life have long struggled to crack the ultimate chicken-and-egg paradox. How did nucleic acids like DNA and RNA--which encode proteins--first form, when proteins are needed for their synthesis? Now, scientists report that they've cooked up molecular hybrids of proteins and nucleic acids that skirt the dreaded paradox. Although it's unknown whether such molecules existed prior to the emergence of life, they offer insight into a chemical pathway that might have helped life arise.

DNA and RNA sport a backbone of sugar and phosphate groups linked to the nucleotide bases that spell out the genetic code. Certain proteins help copy nucleic acids by fashioning complementary strands that carry matching nucleotides. But how could nucleic acids originate without proteins, and vice versa? Proponents of the "RNA World" hypothesis argue that RNA itself was the key because of its dual abilities: It not only carries genetic information but also can catalyze chemical reactions. That view received a big boost earlier this year, when researchers at The Scripps Research Institute in San Diego, California, showed that small RNA fragments can catalyze their own reproduction. "The question remains, how those first RNA molecules appeared," says Luke Leman, a chemist at Scripps who was not part of the study. Other researchers have synthesized DNA and RNA analogs with simpler sugar backbones that may have done the job. Yet those are still complex, lessening the chance that they were the primordial replicating molecules, Leman says.

In hopes of finding something simpler, Leman and colleagues did away with the sugar-phosphate backbones altogether. Instead, they turned to amino acids, protein building blocks that have been shown to assemble under prebiotic conditions. The researchers report online today in Science Express that when they combined just two amino acids, a backbone readily assembled without the need for additional enzymes. They then found that DNA bases could bind to a sulfur group in one of the amino acids, cysteine, creating a protein-DNA hybrid strand. But because the nucleic acid bases attach weakly to the cysteines--think Velcro instead of glue--the bases can jump on and off in solution. As a result, when the researchers placed their hybrids in solution with single strands of DNA and RNA, the hybrids were able to rearrange their nucleic acid makeup to form complementary strands that would bind to the DNAs and RNAs. The researchers discovered that the hybrids could also form strands that would bind to other complementary hybrids, which shows that such molecules have the potential to copy themselves.

"This is very interesting and creative," says Eric Kool, a chemist at Stanford University in Palo Alto, California, who studies nucleic acid analogs. These particular hybrids change so rapidly in solution, it's unclear if they would remain stable long enough to propagate genetic information over several generations. However, Kool says, "It's an idea worth considering."