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.
Highlights
Stepping backward from an RNA world into a nucleic acid depleted epoch, we find ourselves in a presumed protein world, i.e., a world that existed prior to the emergence of RNA as one of life’s building blocks
What molecules might be expected to be instrumental in the chemical evolution toward living systems? Imagine that we were beginning from this ancient prebiotic protein world, how might we select a molecule capable of driving chemical evolution toward the emergence of life? We might choose one that exhibits durability under harsh conditions, a criterion that has been amply demonstrated for prion proteins (PrPs), which has the tendency to misfold into a rogue isoform
Prions or “prion-like proteins” are capable of shape-wise self-replication, meaning that they are selfreplicating beta sheet conformers, able to transfer steric conformation to progeny molecular entities in non-Mendelian fashion [1,2]. The latter are prion-like proteins which behave like prions, but are not prions as exemplified by amyloid-β (Aβ), tau, α-synuclein, and the transactive response DNA-binding protein of 43 kDa (TDP-43)
Summary
Stepping backward from an RNA world into a nucleic acid depleted epoch, we find ourselves in a presumed protein world, i.e., a world that existed prior to the emergence of RNA as one of life’s building blocks. Prions or “prion-like proteins” are capable of shape-wise self-replication, meaning that they are selfreplicating beta sheet conformers, able to transfer steric conformation to progeny molecular entities in non-Mendelian fashion [1,2] The latter are prion-like proteins which behave like prions (by replication and propagation of neurodegenerative disease), but are not prions as exemplified by amyloid-β (Aβ), tau, α-synuclein, and the transactive response DNA-binding protein of 43 kDa (TDP-43). It is highly probable that at the time of the chemical evolution of life, prions and prion-like proteins afforded protection for newly emerging RNA polymers in the Earth’s early harsh environment It is during this time-frame that proteins and RNAs forged a link in the form of ribonucleoproteins (RNPs).
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