95 



nonenzymatic replication of a nucleic acid with a mixed base 

 sequence through several generations of "offspring" has not yet been 

 demonstrated experimentally. 



Thus, the question of whether nucleic acid sequences could 

 evolve by natural selection cannot yet be answered in a prebiotic sys- 

 tem, but experiments using biological enzymes were done to address 

 this question. Replicating systems consisting of the enzyme QB-RNA 

 polymerase and certain small RNA substrates have been used to 

 demonstrate molecular evolution in the test tube. One set of experi- 

 ments started with an RNA substrate that absorbs a dye, ethidium 

 bromide, and is then unable to replicate efficiently. By allowing the 

 RNA to replicate repeatedly in the presence of gradually increasing 

 concentrations of the dye, a new RNA substrate was generated which 

 was no longer inhibited, because it no longer bound the dye-stuff so 

 tightly. This system does not show ^//-replication, because each 

 round of synthesis required the addition of new enzymes. However, 

 experiments like these do show that RNA molecules can adapt by 

 natural selection to bind or reject specific organic molecules, and 

 this is relevant to discussions of the origins of the genetic code. 



Recent experiments demonstrate for the first time that nucleic 

 acids themselves might cause interesting reactions to occur. An RNA 

 strand was observed to "snip out" a portion of its own sequence, 

 apparently without help from enzymes. This cannot really be called 

 catalysis, since the molecule acts on itself, and does so only once for 

 each molecule, but it does suggest that nucleic acids may be capable 

 of at least a few specific catalytic-type reactions. However, in the 

 absence of additional evidence that polynucleotides are able to func- 

 tion as catalysts, one cannot feel confident that nucleic acids could 

 do enough interesting chemistry to "go it alone." 



As with amino acids (fig. V-2), nucleotides possess optically 

 active configuration. Observations that D-nucleosides react more 

 efficiently than L-nucleosides on a nucleic acid template made of 

 D-nucleotides, suggests that nucleotide chains that are made up of 

 monomer with the same enantiomeric configuration can undergo 

 template-directed replication, while "mixed" oligomers cannot. Of 

 course, either all D- or all L-oligomers would replicate equally well, 

 so this result shows only that the components of the primitive 

 nucleic acids must either all have been L-, or all have been D-isomers. 



