Encapsulation of ribozymes inside model protocells leads to faster evolutionary adaptation

Lai, Yei‐Chen; Liu, Ziwei; Chen, Irene

doi:10.1073/pnas.2025054118

Cited by 29 publications

(24 citation statements)

References 115 publications

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“…This autocatalytic cycle may have driven the early evolution of aminoacyl-RNA synthetase ribozymes. In this context, it is noteworthy that in vitro selection and evolution experiments have produced multiple aminoacyl transferase ribozymes with distinct sequences and amino acid substrates, suggesting that ribozyme-catalyzed aminoacylation could have been a function that was relatively easy to evolve in the RNA world ( 38 – 43 ).…”

Section: Discussionmentioning

confidence: 99%

Nonenzymatic assembly of active chimeric ribozymes from aminoacylated RNA oligonucleotides

Radakovic

DasGupta

Wright

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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Aminoacylated transfer RNAs, which harbor a covalent linkage between amino acids and RNA, are a universally conserved feature of life. Because they are essential substrates for ribosomal translation, aminoacylated oligonucleotides must have been present in the RNA world prior to the evolution of the ribosome. One possibility we are exploring is that the aminoacyl ester linkage served another function before being recruited for ribosomal protein synthesis. The nonenzymatic assembly of ribozymes from short RNA oligomers under realistic conditions remains a key challenge in demonstrating a plausible pathway from prebiotic chemistry to the RNA world. Here, we show that aminoacylated RNAs can undergo template-directed assembly into chimeric amino acid–RNA polymers that are active ribozymes. We demonstrate that such chimeric polymers can retain the enzymatic function of their all-RNA counterparts by generating chimeric hammerhead, RNA ligase, and aminoacyl transferase ribozymes. Amino acids with diverse side chains form linkages that are well tolerated within the RNA backbone and, in the case of an aminoacyl transferase, even in its catalytic center, potentially bringing novel functionalities to ribozyme catalysis. Our work suggests that aminoacylation chemistry may have played a role in primordial ribozyme assembly. Increasing the efficiency of this process provides an evolutionary rationale for the emergence of sequence and amino acid–specific aminoacyl-RNA synthetase ribozymes, which could then have generated the substrates for ribosomal protein synthesis.

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Section: Discussionmentioning

confidence: 99%

Nonenzymatic assembly of active chimeric ribozymes from aminoacylated RNA oligonucleotides

Radakovic

DasGupta

Wright

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Thus, compartmentalization provides protection against kleptoparasites. In fact, various studies on RNA-based systems have shown that compartments may also protect against other forms of parasitism. , In addition compartments can enhance the rate of evolutionary adaptation in directed evolution experiments . We already witnessed in our own experiments that parasites may emerge at early stages in the development of life (see above) …”

Section: The Next Stepsmentioning

confidence: 92%

“…46,47 In addition compartments can enhance the rate of evolutionary adaptation in directed evolution experiments. 100 We already witnessed in our own experiments that parasites may emerge at early stages in the development of life (see above). 87 Once compartmentalization has been achieved, the next and possibly final challenge will be to achieve Darwinian evolution of the resulting system in a meaningful way.…”

Section: ■ the Next Stepsmentioning

confidence: 99%

An Approach to the De Novo Synthesis of Life

Otto

2021

Acc. Chem. Res.

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Metrics & MoreArticle Recommendations CONSPECTUS: As the remit of chemistry expands beyond molecules to systems, new synthetic targets appear on the horizon. Among these, life represents perhaps the ultimate synthetic challenge. Building on an increasingly detailed understanding of the inner workings of living systems and advances in organic synthesis and supramolecular chemistry, the de novo synthesis of life (i.e., the construction of a new form of life based on completely synthetic components) is coming within reach. This Account presents our first steps in the journey toward this long-term goal.The synthesis of life requires the functional integration of different subsystems that harbor the different characteristics that are deemed essential to life. The most important of these are self-replication, metabolism, and compartmentalization. Integrating these features into a single system, maintaining this system out of equilibrium, and allowing it to undergo Darwinian evolution should ideally result in the emergence of life. Our journey toward de novo life started with the serendipitous discovery of a new mechanism of self-replication. We found that self-assembly in a mixture of interconverting oligomers is a general way of achieving self-replication, where the assembly process drives the synthesis of the very molecules that assemble. Mechanically induced breakage of the growing replicating assemblies resulted in their exponential growth, which is an important enabler for achieving Darwinian evolution. Through this mechanism, the self-replication of compounds containing peptides, nucleobases, and fully synthetic molecules was achieved. Several examples of evolutionary dynamics have been observed in these systems, including the spontaneous diversification of replicators allowing them to specialize on different food sets, history dependence of replicator composition, and the spontaneous emergence of parasitic behavior. Peptide-based replicator assemblies were found to organize their peptide units in space in a manner that, inadvertently, gives rise to microenvironments that are capable of catalysis of chemical reactions or bindinginduced activation of cofactors. Among the reactions that can be catalyzed by the replicators are ones that produce the precursors from which these replicators grow, amounting to the first examples of the assimilation of a proto-metabolism. Operating these replicators in a chemically fueled out-of-equilibrium replication-destruction regime was found to promote an increase in their molecular complexity. Fueling counteracts the inherent tendency of replicators to evolve toward lower complexity (caused by the fact that smaller replicators tend to replicate faster). Among the remaining steps on the road to de novo life are now to assimilate compartmentalization and achieve open-ended evolution of the resulting system. Success in the synthesis of de novo life, once obtained, will have far-reaching implications for our understanding of what life is, for the search for extraterrestrial life, for ...

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“…[ 108 ] In a recent article, it was shown that the encapsulation of ribozymes inside phospholipid compartments in bulk led to faster evolutionary adaptation compared to ribozymes free in solution. [ 179 ] Nonenzymatic primer extension inside fatty acid compartments was also reported. [ 180 ]…”

Section: Model Protocell Systemsmentioning

confidence: 99%

Protocells: Milestones and Recent Advances

Gözen

Köksal

Põldsalu

et al. 2022

Small

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to assemble astonishing pieces of a complicated puzzle, and realized that further advancement requires input from multiple branches of science, not just biology as the primary life science. Detailed hypotheses have been established about the different scenarios of the emergence of life, including the "RNA world," [1] the "lipid world," [2] "replicator first," [3] "metabolism first," [4][5][6] and others. Although the origin of life is still surrounded by many open questions, our understanding of chemical, physicochemical, and biochemical processes possibly involved in the ancient events preceding Darwinian evolution has seen much progress. We have come a long way from Leduc's physicochemical, inorganic matter-centered view on the beginning of the evolution, yet the matter of the transition from nonliving to living matter still remains largely unsolved, and one of the great scientific problems of our time.The phylogenetic tree of different living domains reflects that life has evolved from simple to more complex structures, i.e., from single-to multicellular organisms. The oldest fossil evidence dating back 3.5 Gy (billion years) comes from stromatolites, [7][8][9][10] microorganismal residues in sedimentary rocks. [11] There appears to be a gap of knowledge regarding the period of evolution between the first primitive hypothetical cells and the fossilized ancient bacteria, which can be considered as an already advanced form of life. [12] It is highly likely that intermediate primitive cell precursors preceded the single-cell organisms. The hypothetical prebiotic structures that were the stepping stone to first self-sustaining living cells are commonly termed "protocells." The possibility of a strong link between the formation of protocells and the origin of life can today be reasonably assumed.One cannot easily proceed in the context of the evolution of cell-based organisms without briefly illuminating the concept of life as we know it on our planet. Over time, different requirements have been proposed for an entity to be considered alive. According to Tibor Ganti's chemoton model, [13] a protocell contains three autocatalytic subsystems: a membrane subsystem that keeps the components together and intact, a metabolic subsystem that captures energy and material resources, and an information subsystem that processes and transfers heritable information to progeny. To be considered alive, these subsystems must be unified and function co-operatively for the survival and evolution of the supersystem. Pohorille and Deamer suggested a modified set of 7 criteria related to the chemoton. [14] At about the same time, Oro defined the requirements by 10 characteristic features. [15] Despite their differences, these descriptions align well with NASA's broader definition of life: "a self-sustaining chemical system capable of Darwinian evolution."The origin of life is still one of humankind's great mysteries. At the transition between nonliving and living matter, protocells, initially featureless aggregates of abiotic matter, ga...

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Encapsulation of ribozymes inside model protocells leads to faster evolutionary adaptation

Cited by 29 publications

References 115 publications

Nonenzymatic assembly of active chimeric ribozymes from aminoacylated RNA oligonucleotides

Nonenzymatic assembly of active chimeric ribozymes from aminoacylated RNA oligonucleotides

An Approach to the De Novo Synthesis of Life

Protocells: Milestones and Recent Advances

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