93 



the yield of oligomer was about 4%. It has recently been shown that 

 simple catalysts can be important in more sophisticated sequence- 

 copying reactions, and certainly contemporary replication enzymes 

 have all been found to contain a metal ion at the active site. 



Template-directed polynucleotide synthesis- The central reac- 

 tion responsible for the stability of inherited characteristics is nucleic 

 acid replication, while a major source of genetic variation is the 

 inaccuracy of this process. This had led many researchers to postu- 

 late that nucleic acid replication, in which a preformed polynucleo- 

 tide template directs the synthesis of a new complementary strand, 

 was the first "genetic" process of the primitive Earth. This theory 

 is appealing, but it should not be accepted as dogma. 



Under certain conditions, organized if unusual helical struc- 

 tures can form between polynucleotides and the complementary 

 monomelic nucleotides or nucleosides. It has been shown that if 

 certain activated condensing agents are added to energize the sys- 

 tem, the monomers can join to form short oligonucleotides. These 

 reactions have established that the Watson-Crick pairing rules apply 

 to these systems too in a nonbiological setting. A detailed analysis 

 of the products of early experiments revealed a startling structural 

 difference between this chemical condensation and the normal 

 enzymatic reaction. (The predominant internucleotide linkages in the 

 chemical product are 2'-S' rather than 3'-5' (fig. V-5), but in con- 

 temporary cells, it is the later linkage which is found almost 

 exclusively.) 



Several years ago, it was shown that the Zn 2 and Pb 2 ions are 

 effective catalysts for energized template-directed synthesis yielding 

 oligomers of guanylic acid with chain lengths in excess of 30. (The 

 Pb 2+ ion gives predominantly 2'-5'-linked products, while the Zn 2 

 ion gives mainly 3'-5'-linked products.) The Pb 2 + reaction has an 

 error rate of about 0.1 in the presence of a "wrong" base, while the 

 Zn 2 reaction has a much lower error rate of 0.005. Thus, the Zn 2 

 catalyzed reaction produces products with the "usual" linking and 

 with an accuracy comparable to the accuracy required by a non- 

 enzymatic replicating system. 



A more recent modification with a slightly different activating 

 group produces a comparable preference for the "usual" 3 -5 

 linkage and comparable accuracy, without requiring Zn 2 . True 



