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From: Martin Harran <martinharran@gmail.com>
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Subject: Re: A chat with AI on OoL
Date: Thu, 12 Dec 2024 14:21:46 +0000
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On Wed, 11 Dec 2024 08:29:08 -0800, erik simpson
<eastside.erik@gmail.com> wrote:

>On 12/10/24 9:46 PM, MarkE wrote:
>> Q1. WHAT ARE THE PROBLEMS WITH PREBIOTIC NUCLEOTIDE SYNTHESIS?
>> 
>> ChatGPT: The synthesis of prebiotic nucleotides—the building blocks of 
>> RNA and DNA—is a key question in understanding the origins of life. 
>> Several challenges make it difficult to explain how nucleotides could 
>> have formed naturally under prebiotic conditions. These challenges include:
>> 
>> 1. Complexity of Nucleotide Synthesis
>> 
>> Nucleotides are composed of three components:
>> 
>>      •    A nitrogenous base (e.g., adenine, guanine, cytosine, thymine, 
>> or uracil)
>> 
>>      •    A five-carbon sugar (ribose in RNA or deoxyribose in DNA)
>> 
>>      •    One or more phosphate groups
>> 
>> The formation of these components, and their subsequent assembly into 
>> nucleotides, is chemically complex and unlikely under simple prebiotic 
>> conditions.
>> 
>> 2. Stability of Ribose
>> 
>>      •    Ribose, the sugar component of RNA, is chemically unstable, 
>> especially under the conditions thought to exist on early Earth (e.g., 
>> high temperatures or in the presence of water).
>> 
>>      •    Ribose is also challenging to produce selectively in prebiotic 
>> conditions; it tends to degrade into other sugars or break down entirely.
>> 
>> 3. Formation of Nitrogenous Bases
>> 
>>      •    Nitrogenous bases like adenine can form under prebiotic 
>> conditions (e.g., through polymerization of hydrogen cyanide), but these 
>> reactions typically require specific conditions (e.g., concentrated 
>> hydrogen cyanide solutions) that may not have been widespread on early 
>> Earth.
>> 
>>      •    Other bases, like cytosine, are more difficult to synthesize 
>> and are less stable.
>> 
>> 4. Coupling of Ribose and Nitrogenous Bases
>> 
>>      •    Attaching a nitrogenous base to ribose to form a nucleoside 
>> (e.g., adenosine) is a thermodynamically unfavorable reaction in aqueous 
>> solutions. This step requires precise conditions and catalysts that may 
>> not have been available prebiotically.
>> 
>> 5. Phosphorylation
>> 
>>      •    Adding a phosphate group to form a complete nucleotide is 
>> another chemically challenging step. Prebiotic phosphate sources are 
>> limited, and phosphorylation typically requires high energy, specific 
>> catalysts, or activating agents.
>> 
>> 6. Chirality Problem
>> 
>>      •    Ribose and other sugars exist as a mixture of left-handed and 
>> right-handed forms (chirality). However, RNA and DNA require exclusively 
>> right-handed ribose (D-ribose). Prebiotic processes do not naturally 
>> favor one chiral form over the other, making this selectivity difficult 
>> to explain.
>> 
>> 7. Dilution and Competition
>> 
>>      •    On early Earth, chemical reactions likely occurred in vast 
>> oceans or other dilute environments. In such settings, precursors of 
>> nucleotides would be diluted and might interact with competing 
>> substances, leading to non-nucleotide byproducts.
>> 
>> 8. UV Sensitivity
>> 
>>      •    Many of the components of nucleotides, such as ribose and 
>> nitrogenous bases, degrade rapidly under ultraviolet (UV) light, which 
>> was abundant on early Earth. This raises questions about how these 
>> components could accumulate in sufficient quantities for nucleotide 
>> synthesis.
>> 
>> Proposed Solutions and Partial Successes
>> 
>> Scientists have proposed various scenarios to address these challenges:
>> 
>>      •    Mineral Catalysis: Certain clays or metal ions may have 
>> facilitated the coupling of sugars, bases, and phosphates.
>> 
>>      •    Alternative Pathways: Non-enzymatic pathways for nucleotide 
>> synthesis have been proposed, such as the formamide pathway or pathways 
>> involving cyclic intermediates.
>> 
>>      •    Localized Environments: Hydrothermal vents, dry-wet cycling in 
>> tidal pools, or evaporating ponds may have concentrated reactants and 
>> created favorable conditions.
>> 
>>      •    Role of RNA Precursors: Some researchers suggest simpler 
>> precursors to RNA (e.g., nucleotide-like molecules) could have emerged 
>> first, bypassing the need for fully-formed nucleotides initially.
>> 
>> Despite these efforts, the prebiotic synthesis of nucleotides remains 
>> one of the most significant challenges in origin-of-life research.
>> 
>> 
>> Q2. HOW LONG FOR A SELF-REPLICATING RNA TO FORM?
>> 
>> ChatGPT: The time required for a self-replicating RNA molecule to form 
>> is highly uncertain and depends on various assumptions about the 
>> conditions on prebiotic Earth. Current estimates vary widely because 
>> they are based on a combination of theoretical calculations, 
>> experimental results, and speculative scenarios. Here are some factors 
>> to consider:
>> 
>> Key Variables
>> 
>>      1.    Chemical Environment
>> 
>>      •    The concentration of RNA precursors (e.g., nucleotides) plays 
>> a crucial role. High concentrations are needed for RNA to polymerize, 
>> but achieving this in a prebiotic setting is challenging due to dilution 
>> in oceans or other large water bodies.
>> 
>>      2.    Catalysts and Conditions
>> 
>>      •    The presence of catalysts, such as mineral surfaces, could 
>> accelerate the formation of RNA. Dry-wet cycles, geothermal activity, or 
>> UV light might also have provided the energy needed for polymerization.
>> 
>>      3.    Randomness of Sequence Assembly
>> 
>>      •    Self-replicating RNA likely requires a specific sequence to 
>> function. The odds of forming such a sequence randomly depend on its 
>> length:
>> 
>>      •    A short RNA molecule with self-replicating ability might be 
>> 30-60 nucleotides long.
>> 
>>      •    The probability of assembling such a sequence randomly is 
>> astronomically low unless specific conditions concentrate and guide the 
>> process.
>> 
>>      4.    Evolutionary Precursor Molecules
>> 
>>      •    It’s unlikely that the first self-replicator appeared in its 
>> fully functional form. Simpler molecules or partial replicators may have 
>> existed, which evolved into more efficient self-replicators over time.
>> 
>>      5.    Timescale of Early Earth
>> 
>>      •    Prebiotic chemistry likely occurred over millions of years, 
>> providing vast amounts of time for rare events to happen.
>> 
>> Theoretical Estimates
>> 
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