Nitrogen heterocycles form peptide nucleic acid precursors in complex prebiotic mixtures

Abstract

The ability to store information is believed to have been crucial for the origin and evolution of life; however, little is known about the genetic polymers relevant to abiogenesis. Nitrogen heterocycles (N-heterocycles) are plausible components of such polymers as they may have been readily available on early Earth and are the means by which the extant genetic macromolecules RNA and DNA store information. Here, we report the reactivity of numerous N-heterocycles in highly complex mixtures, which were generated using a Miller-Urey spark discharge apparatus with either a reducing or neutral atmosphere, to investigate how N-heterocycles are modified under plausible prebiotic conditions. High throughput mass spectrometry was used to identify N-heterocycle adducts. Additionally, tandem mass spectrometry and nuclear magnetic resonance spectroscopy were used to elucidate reaction pathways for select reactions. Remarkably, we found that the majority of N-heterocycles, including the canonical nucleobases, gain short carbonyl side chains in our complex mixtures via a Strecker-like synthesis or Michael addition. These types of N-heterocycle adducts are subunits of the proposed RNA precursor, peptide nucleic acids (PNAs). The ease with which these carbonylated heterocycles form under both reducing and neutral atmospheres is suggestive that PNAs could be prebiotically feasible on early Earth.

Prebiotic oligomerization and self-assembly of structurally diverse xenobiological monomers

“…Although we explored considerable molecular diversity here, there are numerous structural modifications of the compounds in this study that should be similarly polymerizable and may have additional interesting prebiotically relevant properties. The elongation mechanisms discussed here have already been shown to be useful for oligomerizing nucleoside cyclic phosphates 40,41 , and should be applicable to nucleoside analogues as well, of which it seems there could have been a very large prebiotic variety 46,[77][78][79][80] .…”

Depsipeptide Nucleic Acids: Prebiotic Formation, Oligomerization, and Self-Assembly of a New Proto-Nucleic Acid Candidate

“…This synthetic path was also proposed by Miller for the formation of γ-functionalized amino acids such as methionine . A prebiotic precedent for the formation of β-nucleobase-functionalized aldehydes was also recently demonstrated by Rodriguez et al, who found that Miller–Urey-type electrolysis reactions in a reducing atmosphere above aqueous solutions containing nucleobases produced 1,4 addition products of nucleobases (canonical or noncanonical) with Michael acceptors, including acrolein …”

The Grayness of the Origin of Life

“…It also follows traditional Watson-Crick base pairing rules [42]. Notably, recent work shows N-heterocycles synthesized via electric discharge in neutral and reducing atmospheres form carbonyl side chains, lending support to the possible use of PNA in prebiotic systems [44].PNA does not have a charged backbone, a feature that aids in solubility and discourages folding, however, it is able to grow longer than other uncharged RNA analogs [45]. Interestingly, PNA-based life could to some extent be distinguished based on a C:N ratio, which has limited variability in peptides, but significant grayness would persist due to known abiotic synthesis pathways of its components.…”