The Prebiotic Kitchen: A Guide to Composing Prebiotic Soup Recipes to Test Origins of Life Hypotheses

“Prebiotic soup” often features in discussions of origins of life research, both as a theoretical concept when discussing abiological pathways to modern biochemical building blocks and, more recently, as a feedstock in prebiotic chemistry experiments focused on discovering emergent, systems-level processes such as polymerization, encapsulation, and evolution. However, until now, little systematic analysis has gone into the design of well-justified prebiotic mixtures, which are needed to facilitate experimental replicability and comparison among researchers. This paper explores principles that should be considered in choosing chemical mixtures for prebiotic chemistry experiments by reviewing the natural environmental conditions that might have created such mixtures and then suggests reasonable guidelines for designing recipes. We discuss both “assembled” mixtures, which are made by mixing reagent grade chemicals, and “synthesized” mixtures, which are generated directly from diversity-generating primary prebiotic syntheses. We discuss different practical concerns including how to navigate the tremendous uncertainty in the chemistry of the early Earth and how to balance the desire for using prebiotically realistic mixtures with experimental tractability and replicability. Examples of two assembled mixtures, one based on materials likely delivered by carbonaceous meteorites and one based on spark discharge synthesis, are presented to illustrate these challenges. We explore alternative procedures for making synthesized mixtures using recursive chemical reaction systems whose outputs attempt to mimic atmospheric and geochemical synthesis. Other experimental conditions such as pH and ionic strength are also considered. We argue that developing a handful of standardized prebiotic recipes may facilitate coordination among researchers and enable the identification of the most promising mechanisms by which complex prebiotic mixtures were “tamed” during the origin of life to give rise to key living processes such as self-propagation, information processing, and adaptive evolution. We end by advocating for the development of a public prebiotic chemistry database containing experimental methods (including soup recipes), results, and analytical pipelines for analyzing complex prebiotic mixtures.

2,6-diaminopurine promotes repair of DNA lesions under prebiotic conditions

High-yielding and selective prebiotic syntheses of RNA and DNA nucleotides involve UV irradiation to promote the key reaction steps and eradicate biologically irrelevant isomers. While these syntheses were likely enabled by UV-rich prebiotic environment, UV-induced formation of photodamages in polymeric nucleic acids, such as cyclobutane pyrimidine dimers (CPDs), remains the key unresolved issue for the origins of RNA and DNA on Earth. Here, we demonstrate that substitution of adenine with 2,6-diaminopurine enables repair of CPDs with yields reaching 92%. This substantial self-repairing activity originates from excellent electron donating properties of 2,6-diaminopurine in nucleic acid strands. We also show that the deoxyribonucleosides of 2,6-diaminopurine and adenine can be formed under the same prebiotic conditions. Considering that 2,6-diaminopurine was previously shown to increase the rate of nonenzymatic RNA replication, this nucleobase could have played critical roles in the formation of functional and photostable RNA/DNA oligomers in UV-rich prebiotic environments.

The Role of Glycerol and Its Derivatives in the Biochemistry of Living Organisms, and Their Prebiotic Origin and Significance in the Evolution of Life

The emergence and evolution of prebiotic biomolecules on the early Earth remain a question that is considered crucial to understanding the chemistry of the origin of life. Amongst prebiotic molecules, glycerol is significant due to its ubiquity in biochemistry. In this review, we discuss the significance of glycerol and its various derivatives in biochemistry, their plausible roles in the origin and evolution of early cell membranes, and significance in the biochemistry of extremophiles, followed by their prebiotic origin on the early Earth and associated catalytic processes that led to the origin of these compounds. We also discuss various scenarios for the prebiotic syntheses of glycerol and its derivates and evaluate these to determine their relevance to early Earth biochemistry and geochemistry, and recapitulate the utilization of various minerals (including clays), condensation agents, and solvents that could have led to the successful prebiotic genesis of these biomolecules. Furthermore, important prebiotic events such as meteoritic delivery and prebiotic synthesis reactions under astrophysical conditions are also discussed. Finally, we have also highlighted some novel features of glycerol, including glycerol nucleic acid (GNA), in the origin and evolution of the life.

Synthetic connectivity, emergence, and self-regeneration in the network of prebiotic chemistry

The challenge of prebiotic chemistry is to trace the syntheses of life’s key building blocks from a handful of primordial substrates. Here we report a forward-synthesis algorithm that generates a full network of prebiotic chemical reactions accessible from these substrates under generally accepted conditions. This network contains both reported and previously unidentified routes to biotic targets, as well as plausible syntheses of abiotic molecules. It also exhibits three forms of nontrivial chemical emergence, as the molecules within the network can act as catalysts of downstream reaction types; form functional chemical systems, including self-regenerating cycles; and produce surfactants relevant to primitive forms of biological compartmentalization. To support these claims, computer-predicted, prebiotic syntheses of several biotic molecules as well as a multistep, self-regenerative cycle of iminodiacetic acid were validated by experiment.

A carbonate-rich lake solution to the phosphate problem of the origin of life

Phosphate is central to the origin of life because it is a key component of nucleotides in genetic molecules, phospholipid cell membranes, and energy transfer molecules such as adenosine triphosphate. To incorporate phosphate into biomolecules, prebiotic experiments commonly use molar phosphate concentrations to overcome phosphate’s poor reactivity with organics in water. However, phosphate is generally limited to micromolar levels in the environment because it precipitates with calcium as low-solubility apatite minerals. This disparity between laboratory conditions and environmental constraints is an enigma known as “the phosphate problem.” Here we show that carbonate-rich lakes are a marked exception to phosphate-poor natural waters. In principle, modern carbonate-rich lakes could accumulate up to ∼0.1 molal phosphate under steady-state conditions of evaporation and stream inflow because calcium is sequestered into carbonate minerals. This prevents the loss of dissolved phosphate to apatite precipitation. Even higher phosphate concentrations (>1 molal) can form during evaporation in the absence of inflows. On the prebiotic Earth, carbonate-rich lakes were likely abundant and phosphate-rich relative to the present day because of the lack of microbial phosphate sinks and enhanced chemical weathering of phosphate minerals under relatively CO2-rich atmospheres. Furthermore, the prevailing CO2 conditions would have buffered phosphate-rich brines to moderate pH (pH 6.5 to 9). The accumulation of phosphate and other prebiotic reagents at concentration and pH levels relevant to experimental prebiotic syntheses of key biomolecules is a compelling reason to consider carbonate-rich lakes as plausible settings for the origin of life.