Hypercycle (chemistry)

It was introduced in an ordinary differential equation (ODE) form by the Nobel Prize in Chemistry winner Manfred Eigen in 1971[1] and subsequently further extended in collaboration with Peter Schuster.

[2][3] It was proposed as a solution to the error threshold problem encountered during modelling of replicative molecules that hypothetically existed on the primordial Earth (see: abiogenesis).

This can be a solution to the error threshold problem, which states that, in a system without ideal replication, an excess of mutation events would destroy the ability to carry information and prevent the creation of larger and fitter macromolecules.

[6][7][8][9][10][12][13] In 2012, the first experimental proof for the emergence of a cooperative network among fragments of self-assembling ribozymes was published, demonstrating their advantages over self-replicating cycles.

[15] When a model of replicating molecules was created,[1][2] it was found that, for effective storage of information, macromolecules on prebiotic Earth could not exceed a certain threshold length.

[24][25][26] This kind of closed network consisting of self-replicating entities connected by a catalytic positive-feedback loop was named an elementary hypercycle.

Secondly, it reinforces the self-organization of molecules into the hypercycle, allowing the system to evolve without losing information, which solves the error threshold problem.

[2] Analysis of potential molecules that could form the first hypercycles in nature prompted the idea of coupling an information carrier function with enzymatic properties.

At the time of the hypercycle theory formulation, enzymatic properties were attributed only to proteins, while nucleic acids were recognized only as carriers of information.

The other RNA matrices, or just one of their strands, provided translational products which had specific anticodons and were responsible for unique assignment and transportation of amino acids.

[2] Some of them were the consequence of the lack of knowledge about ribozymes, which were discovered a few years after the introduction of the hypercycle concept[16][17] and negated Eigen's assumptions in the strict sense.

The primary of them was that the formation of hypercycles had required the availability of both types of chains: nucleic acids forming a quasispecies population and proteins with enzymatic functions.

Nowadays, taking into account the knowledge about ribozymes, it may be possible that a hypercycle's members were selected from the quasispecies population and the enzymatic function was performed by RNA.

However, Eörs Szathmáry and Irina Gladkih showed that an unconditional coexistence can be obtained even in the case of a non-enzymatic template replication that leads to a subexponential or a parabolic growth.

The coexistence of various non-enzymatically replicating sequences could help to maintain a sufficient diversity of RNA modules used later to build molecules with catalytic functions.

However, in reality, the cooperation of hypercycles would be extremely difficult, because it requires the existence of a complicated multi-step biochemical mechanism or an incorporation of more than two types of molecules.

[29] They proposed the so-called package model in which one type of a polymerase is sufficient and copies all polynucleotide chains that contain a special recognition motif.

[30] This problem, however, raised more objections, and Eörs Szathmáry and László Demeter reconsidered whether packing hypercycles into compartments is a necessary intermediate stage of the evolution.

Numerical simulations showed that when stochastic effects are taken into account, compartmentalization is sufficient to integrate information dispersed in competitive replicators without the need for hypercycle organization.

Ribozymes potentially serving as templates and catalysers of replication can be considered components of quasispecies that can self-organize into a hypercycle without the need to invent a translation process.

[41] Altogether, the results concerning the RNA ligase's catalytic domain and the acyltransferase ribozyme are in agreement with the estimated upper limit of 100 nucleotides set by the error threshold problem.

[42] Forty years after the publication of Manfred Eigen's primary work dedicated to hypercycles,[1] Nilesh Vaidya and colleagues showed experimentally that ribozymes can form catalytic cycles and networks capable of expanding their sizes by incorporating new members.

[43] In their experiments, Vaidya et al. used an Azoarcus group I intron ribozyme that, when fragmented, has an ability to self-assemble by catalysing recombination reactions in an autocatalytic manner.

Results obtained from experiments by Vaidya et al. gave a glimpse on how inefficient prebiotic polymerases, capable of synthesizing only short oligomers, could be sufficient at the pre-life stage to spark off life.

This could happen because coupling the synthesis of short RNA fragments by the first ribozymal polymerases to a system capable of self-assembly not only enables building longer sequences but also allows exploiting the fitness space more efficiently with the use of the recombination process.

Shortly after Eigen and Schuster published their main work regarding hypercycles,[2] John Maynard Smith raised an objection that the catalytic support for the replication given to other molecules is altruistic.

[2] Several researchers proposed a solution to these problems by introducing space into the initial model either explicitly[6][13][48][49] or in the form of a spatial segregation within compartments.

[12] Another model based on cellular automata, taking into account a simpler replicating network of continuously mutating parasites and their interactions with one replicase species, was proposed by Takeuchi and Hogeweg[7] and exhibited an emergent travelling wave pattern.

[53] The hypercycle is just one of several current theories of life, including the chemoton[54] of Tibor Gánti, the (M,R) systems[55][56] of Robert Rosen, autopoiesis (or self-building)[57] of Humberto Maturana and Francisco Varela, and the autocatalytic sets[58] of Stuart Kauffman, similar to an earlier proposal by Freeman Dyson.

This article was adapted from the following source under a CC BY 4.0 license (2016) (reviewer reports): Natalia Szostak; Szymon Wasik; Jacek Blazewicz (7 April 2016).