Lack of evolvability in self-sustaining autocatalytic networks constraints metabolism-first scenarios for the origin of life

Abstract

A basic property of life is its capacity to experience Darwinian evolution. The replicator concept is at the core of genetics-first theories of the origin of life, which suggest that self-replicating oligonucleotides or their similar ancestors may have been the first "living" systems and may have led to the evolution of an RNA world. But problems with the nonenzymatic synthesis of biopolymers and the origin of template replication have spurred the alternative metabolism-first scenario, where self-reproducing and evolving proto-metabolic networks are assumed to have predated self-replicating genes. Recent theoretical work shows that "compositional genomes" (i.e., the counts of different molecular species in an assembly) are able to propagate compositional information and can provide a setup on which natural selection acts. Accordingly, if we stick to the notion of replicator as an entity that passes on its structure largely intact in successive replications, those macromolecular aggregates could be dubbed "ensemble replicators" (composomes) and quite different from the more familiar genes and memes. In sharp contrast with template-dependent replication dynamics, we demonstrate here that replication of compositional information is so inaccurate that fitter compositional genomes cannot be maintained by selection and, therefore, the system lacks evolvability (i.e., it cannot substantially depart from the asymptotic steady-state solution already built-in in the dynamical equations). We conclude that this fundamental limitation of ensemble replicators cautions against metabolism-first theories of the origin of life, although ancient metabolic systems could have provided a stable habitat within which polymer replicators later evolved.

Fig. 1.

Three-dimensional plot of Eigen's fitness matrix in Eq. 6. GARD assemblies were characterized as 10-long vectors and distinguished by their initial composition of molecules (). The values for the forward and backward rate constants as described by Eq. 1 with were and (i.e., we have neglected decay of assemblies), respectively. The elements of the matrix for the catalytic enhancement factors were sampled from a log-normal distribution with parameters and as in ref. . As a legacy, the elements in the matrix () have mean 18,157.3 and variance , and some off-diagonal elements can be as large, or even larger, than the diagonal elements. The inset plot shows the particular distribution for row 94; that is, the values that lead to the increase in frequency of the most frequent composome (SI Section A). The highest peaks are in the distribution range between compositional assemblies and , which means that the outflow from these compositions to the equilibrium frequency of the leading composome is greater than the bona fide replication of the leading composome itself.

Fig. 2.

The quasicompartmentalization of the matrices of molecular repertoires (A) and (B) . Nodes marked with the same color belong to the same quasicompartment. The widths of links correspond to the interaction strength. For the large matrix (B), only interactions stronger than are shown for simplicity. Quasicompartments are formed where the few large values from a log-normal distribution fall. The figure was drawn using NetDraw (42).

Fig. 3.

The time-correlation matrix of values (Eq. 2) along 54 generations derived from computer simulations of the GARD model using the matrix in Fig. 2B. Only individuals before splitting are included in the analysis. Purple squares mark QSSs where three different composomes (A, B, and C) persist.

Fig. 4.

Similarity of composomes to quasicompartments for 54 generations. Only individuals before splitting are included in the analysis. Similarity is calculated as the proportion of molecules within a composome that belong to each dominant quasicompartment. A, B, and C mark the three different composomes in Fig. 3; 8, 11, 12, 17, and 20 mark the five different quasicompartments. Similarity for the other 23 compartments remained low and therefore is not shown.