Replication complementary

Figure 2. The logic of complementary replication and mutation. Template-induced synthesis of RNA is based on nucleotide complementarity (G h C and A = U) in the double helix. The synthesis starts at the 5 -end of the template and adds nucleotide after nucleotide to the growing chain. In this way a negative copy is obtained, being the minus- or plus-strand when a plus- or a minus-strand was the template, respectively. Dissociation of the double-helical plus-minus-duplex completes complementary replication. Three classes of...

A similar approach is possible when considering questions in the lipid world the issue is however complicated by the fact that we need to tackle the problem of reflexive auto catalysis. This has also precedence in the literature the reflexively autocatalytic protein networks (e.g. [25]) are perhaps the best known example. We hasten to point out that nobody has seen a real reflexively autocatalytic protein set, apart from very small ones where replication is in fact modular and analogous to the complementary replication of oligonucleotides [26]. Let us see whether one can be more hopeful regarding autocatalytic lipid sets. 

Figure 3. Reaction scheme of complementary replication of single-stranded RNA. Reaction consists of four phases initiation, elongation, product release, and template reactivation. Reaction product (replica) is complementary to template. Substrates are four nucleoside triphosphates ATP, GTP, UTP, and CTP. Pyrophosphate (pp) is waste product at each step of incorporation. Symbols /, RNA template chain E, enzyme (replicase) P, growing RNA replica chain. Indexes A, association D, dissociaton S, substrate F, phosphate diester bond formation PR, product release the numbers 3, or 5, refer to end of the RNA chain to which the enzyme binds or from which it dissociates (cf. ref. 10).

Replication degenerates to a random production of sequences in the limit q- j and corresponds to the limit r->oo, the case of maximum disorder. Direct and complementary replication (see also part C) are the analogs of ferro- and antiferromagnetic cases of the spin system. In the range q < 1 we have K<0, which corresponds to the condition pj<0 for ferromagnetic interaction. For complementary or plus-minus replication, we have... 

Figure 10. Quasi-species as function of single-digit accuracy of replication (q) for chain v = 5. We plot relative stationary concentration of master sequence ( (,),fum of relative stationary concentrations of alt one-error mutants ((i), of all two-error mutants ( j), etc. Note that we have only one five-error mutant 7,5, = /s, in this particular example. We observe selection of master sequence at g = 1. Then relative concentration of master sequence decreases with decreasing q. At value q = 0.5 all sequences are present in equal concentrations. Hence, sums of concentrations of two- and three-error mutants are largest—they have statistical weight of 10—those of the one-and four-error mutants are half as large—they have statistical weight of 5—and finally master sequence 7q and its complementary sequence, the five-error mutant /ji, are present in relative concentration ofonly. At q = 0 we have selection o( master pair", which consists of/o and /31 in our example. Thus we have direct replication with errors in range 1 > g > 0.5 and complementary replication with errors in range 0 < q < 0.5. Rate constants chosen as Aq = 10[U ] and A = 1 [t ] for all mutants Ic 0. Here we denote arbitrary reciprocal time unit by [t" ]. All degradation rate constants were put equal 7>o = D, = Dj = = D31 = 0.

Increasing chain length changes the general features of the fi, q plots rather drastically. For v = 10 the range of random replication appears to be substantially wider (Figure 11). The (fi, q curves are almost horizontal on both sides of the maximum irregularity condition at q = 0.5. In addition, the transitions from direct to random replication and from random to complementary replication are rather sharp. We are now in a position to compare the minimum accuracy of replication that we derived in Section III by perturbation theory with the exact population dependence on q. From Eqs. (III.l) and (III.4) we find (D = 0 k = 0,1,. . . , n)... 

Figure 11. Quasi-species as function of single-digit accuracy of replication (q) for chain length V = 10. Computations were performed in complete analogy to those shown in Figure 10. Note that range of "random replication" has increased substantially compared to case v = 5. We observe fairly sharp transitions between direct and random replication at critical value q = and between random and complementary replication aX q =...

On the other hand, high accuracy in complementary replication is characterized by low q values. Here, we have a maximum q value that sets a limit to the errors tolerated in complementary replication. From perturbation theory we derive... 

The second example (Figure 15) considers two distant degenerate sequences Iq and /30, with d(0, 30) = 4. Accordingly, we observe selection in the limit q->l. The sequence with more efficient one-error mutants (/30) is selected. In the domain of complementary replication we are dealing with two... 

The third example (Figure 16) behaves in a very similar manner to the second in the range of direct replication. But the rate constants have been changed such that we now have two degenerate pairs of complementary sequences in the limit -+0, (/q, /31) and (/j, /30). These two pairs have a Hamming distance d=l, and we expect equal concentrations of /q and /30 and of 11 and 731, respectively. It is interesting to note that these concentrations remain almost the same nearly for the whole domain of complementary replication. 

In the experiment, the components of the new replicator were mixed with the components of our biphenyl replicator [42], and we expected to generate four self-complementary, replicating systems. We assumed that self-complementarity of structure was sufficient for replication after all, had not all our replicators (and those of others [43]) shared this feature All possible combinations of (4), (8), (41) and (40) were duly synthesized (Figure 25), and their behavior taught us a lesson concerning molecular shape. One of the shuffled replicators, the adenine-thymine product (43), resembles DNA, but with an amide backbone. It turned out to be the most effective synthetic replicator we have encountered to date (perhaps this is not mere coincidence). The other shuffled replicator (44) was unable to catalyze its own formation. 

Doi and Spiegelman (1963) showed that RNA molecules of phage MS2, when entering cells of E.coli (labeled with and N ), despite active autoreplication (through a phase of complementary replication) and template activity, do not fragment to begin with. 

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