Last month, I attended the Biomedical Research Academy at the University of Pennsylvania. There, I listened to a lecture that really stuck with me: The RNA World. The RNA World theory accounts for the most fundamental procedure in all life: the central dogma, or the process of transcribing DNA to RNA that is translated into protein. The theory suggests that machinery involved in the central dogma grew out of an RNA World–a world where RNA acted both as the genetic storage material and the machinery to perform rudimentary biochemical reactions.
In that lecture, we played a “bead game” to model the early instances of evolution and natural selection. The rules stated individual beads, or, “nucleotides” would be randomly added by rolling a die. Once a predetermined “replication” or “destroy” nucleotide sequence was achieved, the players could “replicate” the strand of beads or “destroy” another group’s strand. The team with the most strands at the end of the period would win. (Unfortunately, my team did not win…) However, the winning team had both “replication” and “destroy” sequences that allowed them to be competitive against teams that did not achieve those sequences.
Although simple, the bead game works as an accurate model to real RNA: the beads stored information in the order they were placed and certain bead sequences produced functions that increased the strand’s fitness. Sequences of complementary base pairs in real RNA can bond to each other, causing the RNA to fold over itself. As we know with protein synthesis, folding into complicated structures can generate a steric & biochemical effect that may have allowed early RNA “organisms” to replicate and destroy. “Organisms” that gained more functions that increased their fitness would outcompete other, less fit “organisms”.
Our class discussed traits that would benefit an RNA “organism” (and their analogous bead game abilities). For example, increasing the rate a strand could replicate or destroy other strands would be analogous to RNA evolving more efficient ways to carry out its functions. My favorite was the proposed ability to use beads & string from other groups’ destroyed strands, mirroring an RNA “eating” another RNA biochemically.
Eventually, a single macromolecule acting as the genetic information and functional machine limited sustained growth and evolution of the RNA “organism”. Thus, “organisms” that could delegate tasks to other molecules outcompeted simpler, single-stranded RNA.
In vitro RNA experiments produced RNA molecules that could bind tightly to amino acids. There is evidence indicating RNA molecules that bound selectively to a certain amino acid would have an excess of that amino acid’s codon. Thus began the growth of RNA to protein synthesis: RNA acted as template for amino acid-associated RNA molecules to generate a polypeptide. Now, these “amino acid-associated RNA” developed into tRNA. Modern tRNA retains qualities of the old “RNA organisms”: acting as machinery to build protein and contain genetic information through anticodons.
The other half of the central dogma, DNA to RNA transcription, also proved to be a competitive advantage. The theory that RNA developed before DNA is supported by the fact that ribose can be readily synthesized from formaldehyde (HCHO) in the conditions of a young Earth. Deoxyribose, on the other hand, requires an enzyme to be synthesized. Although requiring more effort to be created, deoxyribose backbones were much stronger and were more stable than ribose counterparts. As “RNA organisms” grew more complicated, long sequences of genetic information with ribose backbones were simply unsustainable. The switch to DNA as the genetic storage macromolecule provided an edge in natural selection.
The RNA Theory, to me, is more than just a theory. It is a fairytale that tells the story of the origin of complicated life. The lecture reminded me of why my passion is in biology: it is a long-winded and zig-zagging fantastic novel that we have yet to finish reading.
