Sequencing the origins of life

Jia, Tony Z.; Nishikawa, Shota; Fujishima, Kosuke

doi:10.1016/j.bbadva.2022.100049

Cited by 5 publications

(3 citation statements)

References 170 publications

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“…Similarly, the predominant method of experimental analysis is gel electrophoresis, [28] which provides no information on the exact identity of the nucleobase incorporated at each extension step. This is likely due to gel electrophoresis being much more accessible, straightforward, and rapid to perform than techniques such as MALDI [19,26] or nanopore sequencing [29] which would give sequence information and therefore information on fidelity. This bias in analysis was highlighted by Duzdevich and co-workers in their work to generate a deep sequencing methodology for primer extension.…”

Section: Impact On Sequence Selectivitymentioning

confidence: 99%

The Impact of Activating Agents on Non‐Enzymatic Nucleic Acid Extension Reactions

Callaghan,

Sherrell,

Ellis

2024

ChemBioChem

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Non‐enzymatic template‐directed primer extension is increasingly being studied for the production of RNA and DNA. These reactions benefit from producing RNA or DNA in an aqueous, protecting group free system, without the need for expensive enzymes. However, these primer extension reactions suffer from a lack of fidelity, low reaction rates, low overall yields, and short primer extension lengths. This review outlines a detailed mechanistic pathway for non‐enzymatic template‐directed primer extension and presents a review of the thermodynamic driving forces involved in entropic templating. Through the lens of entropic templating, the rate and fidelity of a reaction are shown to be intrinsically linked to the reactivity of the activating agent used. Thus, a strategy is discussed for the optimization of non‐enzymatic template‐directed primer extension, providing a path towards cost‐effective in vitro synthesis of RNA and DNA.

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Section: Impact On Sequence Selectivitymentioning

confidence: 99%

The Impact of Activating Agents on Non‐Enzymatic Nucleic Acid Extension Reactions

Callaghan,

Sherrell,

Ellis

2024

ChemBioChem

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“…[ 120 ] On early Earth, a number of other non‐peptide‐based plausible types of counter‐ion could have also existed, one of which may have been in the form of nucleotides or nucleic acids. [ 121 ] There has been much speculation about the existence of nucleotides on early Earth, especially through investigation of the RNA World theory of the origins of life (also plausible would be a pre‐RNA [ 122 ] or an RNA–DNA [ 123 ] World). Researchers have uncovered many ways by which such nucleotides could have been synthesized, including by spark discharge, [ 124 ] on meteorites, [ 125 ] or as a result of syntheses in cyanosulfidic environments.…”

Section: Aspects Of Primitive Llpsmentioning

confidence: 99%

A compositional view comparing modern biological condensates and primitive phase‐separated compartments

Cannelli,

Gupta,

Nguyen

et al. 2023

Peptide Science

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Liquid–liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares compositional aspects of modern biological condensates and primitive LLPS is necessary. Here, we first focus on membraneless organelles composed of intrinsically disordered proteins (IDPs) and nucleic acids. Then, as a parallel, we explore primitive membraneless compartments composed of simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare composition of modern biological condensates and primitive phase‐separated compartments, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane‐bound cells. This review aims to provide a compositional comparison of modern and primitive phase‐separated structures in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed.

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“…Earth, a number of other non-peptide-based plausible types of counter-ion could have also existed, one of which may have been in the form of nucleotides or nucleic acids. [126] There has been much speculation about the existence of nucleotides on early Earth, especially through investigation of the RNA World theory of the origin of life (also plausible would be a pre-RNA [127] or an RNA-DNA [128] World), and researchers have uncovered many ways by which such nucleotides could have been synthesized, including by spark discharge, [129] on meteorites, [130] or as a result of syntheses in cyanosulfidic environments. [131] AMP, ADP, and ATP have all been observed to form in mineral pores, [132] suggesting that nucleotide mono-, di-, and tri-phosphates could have plausibly existed.…”

Section: Primitive Biopolymer-based Coacervatesmentioning

confidence: 99%

Bridging the Gap Between Primitive and Modern Phase Separation

Cannelli,

Gupta,

Nguyen

et al. 2023

Preprint

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Liquid-liquid phase separation (LLPS) is a process that often occurs due to binding between oppositely charged biopolymers, and has gained increasing attention recently due to their ubiquity in biological systems and ability to direct essential cellular processes. For example, aberrant biological LLPS can lead to the emergence and progression of various diseases and disorders, and many significant advances have been made in the biological phase separation field. However, while these discoveries in biology are recent, the field of origins of life has been investigating LLPS for nearly 100 years, ever since the first suggestions by Oparin and Haldane that primitive LLPS could have been precursors to the first cells on Earth. Since then, a significant amount of work has been done to elucidate different primitive LLPS systems that could have been relevant as protocellular models. Given the structural similarities between primitive LLPS and modern membraneless organelles, there may even be an evolutionary link between the two, although this remains a question to be answered. Nevertheless, in order to answer this, a source that compares aspects of modern and primitive LLPS is necessary. Here, we first focus on the assembly of membraneless organelles from intrinsically disordered proteins (IDPs) and nucleic acids, and discuss an example by which aberrant LLPS can result in progression of a disease (tumorigenesis). Then, as a parallel, we explore assembly of primitive membraneless compartments from simple biopolymers such as short peptides and nucleic acids. This is followed by a discussion of how the first biomolecules on Earth may have originated, analyzing the environmental and chemical conditions that could have favored primitive LLPS processes. Finally, we directly compare various aspects of LLPS assembly from both a primitive and a modern perspective, further discussing the potential of primitive IDPs on early Earth, but also the evolution from membraneless to membrane-bound cells. This review aims to provide a comparison of modern and primitive phase separation, including assembly and function, in order to help researchers in both fields understand the current state of knowledge, how this knowledge evolved, and the current gaps that need to be further addressed.

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Sequencing the origins of life

Cited by 5 publications

References 170 publications

The Impact of Activating Agents on Non‐Enzymatic Nucleic Acid Extension Reactions

The Impact of Activating Agents on Non‐Enzymatic Nucleic Acid Extension Reactions

A compositional view comparing modern biological condensates and primitive phase‐separated compartments

Bridging the Gap Between Primitive and Modern Phase Separation

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