Towards open-ended evolution in self-replicating molecular systems

Abstract

In this review we discuss systems of self-replicating molecules in the context of the origin of life and the synthesis of de novo life. One of the important aspects of life is the ability to reproduce and evolve continuously. In this review we consider some of the prerequisites for obtaining unbounded evolution of self-replicating molecules and describe some recent advances in this field. While evolution experiments involving self-replicating molecules have shown promising results, true open-ended evolution has not been realized so far. A full understanding of the requirements for open-ended evolution would provide a better understanding of how life could have emerged from molecular building blocks and what is needed to create a minimal form of life in the laboratory.

Keywords: autocatalysis; open-ended evolution; origin of life; self-replication; synthetic life.

Figure 1

Three processes involved in Darwinian evolution. Species must be replicated to obtain a large population. During the replication process mutations can occur, on which natural or artificial selection can then take place.

Figure 2

Minimal system for self-replication. Building blocks A and B can react to form either template T or its inactive counterpart T_inactive. The formation of template T can direct A and B to a configuration in which they are in close proximity, accelerating the reaction between A and B leading to the formation of the [T∙T] complex. Dissociation of this complex completes the replication cycle of the initial template molecule.

Figure 3

A cross-catalytic replication scheme in which the formation of one template stimulates the formation of a different, complementary template.

Figure 4

The first oligonucleotide capable of template directed self-replication without the need of enzymes. The depicted hexamer template T is formed from two trimer building blocks and catalyzes its own formation. Self-reproduction of this molecule was shown to result in parabolic growth of the template concentration [30].

Figure 5

Replication involving the SPREAD technique which prevents product inhibition. (1) A template molecule is immobilized on a solid support and (2, 3) a complementary copy is produced by template-directed replication. Finally the copied strand is (4) released from the template and is in turn immobilized [33].

Figure 6

Figure showing (a) a coiled coil motif due to hydrophobic interactions between hydrophobic amino acids in the individual helices. (b) Helical-wheel diagram showing how the hydrophobic amino acids situated on the a and d sites can interact with each other to form the coiled coil [34].

Figure 7

Self-replication of a helical peptide. Molecular recognition leads to the formation of a stable coiled coil structure from smaller peptide fragments. Depending on the length and stability of the coiled coil structure, the template-duplex dissociates in the original template and a copy [37].

Figure 8

(a) Cross-catalyzed replication of template molecules E and E’ from their building blocks A⁽’⁾ and B⁽’⁾. (b) Secondary structure of the template duplex. The curved arrow denotes the site of ligation of the building blocks, the dashed boxes include the sequences to be mutated and the solid lines indicate the sites of the G∙U base pairs inducing the wobble that enhances catalytic activity. (c) The altered sequences of the 12 different template molecules, the E’ molecules have complementary sequences in the base pairing part (horizontal) and identical sequences in the catalytic part (vertical). Dark circles denote the differences relative to E1 [45].

Figure 9

Distribution of the species present in the reaction mixture after 20 serial transfers. E and E’ molecules are represented by the dark and light shaded bars, respectively. Note how certain species have come to dominate the population, particularly A5B3. Moreover, only 7 molecules were found to be paired to their original partner (corresponding to the shaded diagonal) [45].

Figure 10

(a) Secondary structure of the Azoarcus ribozyme consisting of four different strands of RNA, W, X, Y, and Z. Self-replication is mediated by recognition of the target sites by the IGS (grey boxes), leading to ligation of the strands. The dashed line indicates the catalytic core of the resulting ribozyme. (b) Cooperative replicating system. The formation of the covalent ribozyme E3 from the non-covalent I3 complex is catalyzed by E2 ribozyme. The formation of this E2 is in turn catalyzed by E1, which is catalyzed by E3, resulting in a cyclic dependence. Numbers above the arrows denote the advantage of cooperativity [46].

Figure 11

(a) The different combinations of IGS strands, tags and break junction give rise to a total of 48 different pairs. (b) Graph showing the frequency of autocatalytic replicators (dashed, crosses), the two-membered cycles (dashed, dots; ×10) and the three-membered cycles (solid; ×10.000) over time. Note the emergence of the more complex three-membered cycles at later times [46].

Figure 12

Figure depicting (a) building blocks consisting of a peptide attached to an aromatic ring. Building blocks 1 and 2 differ only in the nature of the penultimate amino acid. (b) The building blocks can form macrocycles of different sizes upon oxidation, which can exchange building blocks with each other. (c) Schematic representation showing how building blocks oxidize to form macrocycles that in turn form stacks due to β-sheet formation. Stacks grow from their ends and fragment upon agitation, leading to more fiber ends and faster growth [52].

Figure 13

Plot showing the relative concentrations of set I (red), set II (blue) and the link between them; (1)₃(2)₃ (purple). Note how at first only set I is present in the mixture, while at some point this set gives rise to the descendant set II. [52]