The beginning of life on Earth is a hotly contested area of science (not to mention religion); with current theories focusing on how RNA (ribonucleic acid)-like molecules developed into a more complex form of RNA-based life, which then transformed into cellular life based on DNA (deoxyribonucleic acid) and proteins. Now, an accelerated in vitro experiment shows how an RNA enzyme develops into a DNA enzyme without losing its original function. The experiment, described as an "evolutionary conversion," is considered a breakthrough, as it presents scientists with a contemporary understanding of how complex life may have evolved out of the earliest primordial sludge. The transference of sequence information between two different classes of nucleic acid-like molecules - such as RNA and DNA - is considered uncomplicated, because it simply follows a procedure of double helix pairing. By comparison, catalytic function is considerably trickier, as it cannot be expressed sequentially. But research conducted by Scripps researcher Gerald F. Joyce, published in the online journal Chemistry & Biology, shows that the "evolutionary conversion" of an RNA enzyme to a DNA enzyme with the same function is possible through the acquisition of a few critical mutations.
"During early life on Earth, both genetic information and catalytic function were thought to reside only in RNA. In our study, the evolutionary transition from RNA to a DNA enzyme represents a genuine change, rather than a simple expansion, of the chemical basis for catalytic function. This means that similar evolutionary pathways may exist between other classes of nucleic acid-like molecules. These findings could help answer some fundamental questions concerning the basic structure of life and how it evolved over time," Joyce explained.
In 1970, Nobel Laureate Francis Crick, who discovered the double helix structure of DNA, said that all known organisms function according to the "central dogma" of molecular biology, and that the transfer of sequential genetic information proceeds from nucleic acid to nucleic acid and from nucleic acid to protein. But this does not account for contemporary biological "dogma" that states catalytic function does not transfer sequentially. Joyce's study, however, shows that catalytic function can be transmitted sequentially between two different nucleic acid-like molecules, if the existence of a pre-RNA molecule is assumed.
This is a significant discovery, because if correct, it explains how pre-RNA molecules are able to cross-pair in order to allow genetic information to flow from pre-RNA molecules to RNA. Joyce claims that the catalytic function of these early enzymes may have been passed on to a matching RNA enzyme subsequent to the acquisition of a minimum of crucial mutations. Joyce believes this catalytic process is analogous to the evolutionary change of a ribozyme to a deoxyribozyme through random mutation and selection.
In order to manufacture the accelerated process, Joyce converted an RNA ribozyme to a corresponding deoxyribozyme through in vitro evolution. Joyce first prepared the ribozyme as a DNA molecule with the same RNA sequence, but without any noticeable catalytic activity. He then prepared a large batch of DNA with randomized variations so that continual cycles of in vitro evolution could take place. By the end of the experiment, Joyce found that he had a deoxyribozyme capable of catalytic activity similar to that of the original ribozyme.
"The use of in vitro evolution provides the means to convert a ribozyme to a corresponding deoxyribozyme rapidly," Joyce said. "In the laboratory these procedures allow us to carry out many generations of test tube evolution. The resulting molecules have interesting catalytic properties, they teach us something new about evolution, and they have potential application as therapeutic and diagnostic agents."
Source: Scripps Research Institute
