The Way forward for the Origin of Life: Prions and Prion-Like Molecules First Hypothesis

Abstract

In this paper the hypothesis that prions and prion-like molecules could have initiated the chemical evolutionary process which led to the eventual emergence of life is reappraised. The prions first hypothesis is a specific application of the protein-first hypothesis which asserts that protein-based chemical evolution preceded the evolution of genetic encoding processes. This genetics-first hypothesis asserts that an "RNA-world era" came before protein-based chemical evolution and rests on a singular premise that molecules such as RNA, acetyl-CoA, and NAD are relics of a long line of chemical evolutionary processes preceding the Last Universal Common Ancestor (LUCA). Nevertheless, we assert that prions and prion-like molecules may also be relics of chemical evolutionary processes preceding LUCA. To support this assertion is the observation that prions and prion-like molecules are involved in a plethora of activities in contemporary biology in both complex (eukaryotes) and primitive life forms. Furthermore, a literature survey reveals that small RNA virus genomes harbor information about prions (and amyloids). If, as has been presumed by proponents of the genetics-first hypotheses, small viruses were present during an RNA world era and were involved in some of the earliest evolutionary processes, this places prions and prion-like molecules potentially at the heart of the chemical evolutionary process whose eventual outcome was life. We deliberate on the case for prions and prion-like molecules as the frontier molecules at the dawn of evolution of living systems.

Keywords: LUCA; RNA; RNA viruses; amyloids; chemical relics; origin of life; prions.

Figure 1

Upper panel: shows thirteen amino acids that were thought to be present during the chemical evolution of life as reported in Table 1 column (g) [14]. Lower panel: shows aspartic acid has net protonated amide ($$N{H}_2{H}^{+}$$) side chains in (a–c) at various pH including a zwitterion (b) and a zero charge at pH 2.8. It has been reported that both aspartic acid and glutamic acid are particularly relevant in 65% of catalyst residues because of their ionic charges, remembering that it is the interplay of electrons which brings about reactions—cf the three hydrophobic amino acids used in Ikehara’s experiment Gly > Ala > Val. Likewise, serine and threonine (with their polar, uncharged, side chains), and tyrosine are also important in 27% of catalyst residues. To complete the comparison, hydrophobic amino acids (Gly, Ala, Val, Pro, Leu, and Ile) feature only 8% of the time at the active sites of enzymes [16,18]. In (d) aspartic acid represents as having overall charge of −2 when the pH exceeds 10.0.

Figure 2

(a) Formation of secondary level structures in the form of α-helices and β-sheets. The red dotted lines are an indication of the presence of hydrogen bonds between two peptide strands. The amino acids: glycine, alanine, aspartate and proline are widely distributed in α-helices; valine, isoleucine and tryptophan are commonly found in β-sheets [3]. Noting that tryptophan is not included in the top thirteen prebiotic amino acids indicated in Table 1. This raises two possibilities. Firstly, that initial proteins were much “simpler”, being made from only the thirteen amino acids. Secondly, that tryptophan is absent in the chemical inventory of comets [14] and was, thus, acquired later during the chemical evolution, meaning that they are probably biogenic in nature [18]. (b) within the context of PrPs, the PrP^Scs precipitate out into tightly packed tertiary structures which means they are able to withstand harsh environmental conditions when compared to RNA shapes. This figure also depicts that PrP^C is more α-helices orientated than β-sheets. This situation is reversed in PrP^Sc.

Figure 3

Pictorial representation of major events during the emergence of the three domains of life, namely, Archaea, Bacteria, and Eukarya. It is highly probable that both Archaea and Bacteria emerged from two resilient LUCAs based on their cell membrane compositions and biochemistries (see [50], with Eukarya being a chimera of the former two domains.) It is believed that viruses had an independent origin, probably emerging during the RNA world era.

Figure 4

Depicts the formation of a pincer when poly-A-RNA attaches at the 21–31 amino acid segment on the PrP^c. The pincer is eventually removed and dissolved. The figure also illustrates an earliest possible example of interaction between peptides and nucleic acids.