It is proposed that early replication and protein biosynthesis were inseparable functions performed by a single ancient RNA molecule: the riboreplisome, and this hypothesis addresses fundamental challenges facing RNA world, protein world, and RNA-protein co-evolution theories.
Abstract
Translation of the genetic code into proteins is universal across life, with ribosomes serving as the ancient molecular machines enabling this information transformation. We propose that early replication and protein biosynthesis were inseparable functions performed by a single ancient RNA molecule: the riboreplisome. This hypothesis addresses fundamental challenges facing RNA world, protein world, and RNA-protein co-evolution theories -- particularly the problem of non-Darwinian starting points and the interdependence of replication and translation machineries. We present a 12-step evolutionary pathway from simple RNA replicase to proto-ribosome, supported by quantitative modelling demonstrating that only two steps require non-Darwinian transitions while the remaining ten proceed through standard selection. The single-molecule riboreplisome architecture provides an approximately 6-fold evolutionary advantage over multi-component"RNA soup"scenarios, principally by maintaining genetic linkage and retaining catalytic products close to the replicating genome (resisting diffusion loss); structural resistance to parasitic"cheater"molecules follows as a corollary. The riboreplisome framework explains the origins of ribosomal, transfer, and messenger RNA as derivatives of a single ancestral molecule, while providing a driving force for cellular compartmentalisation. Although the original riboreplisome is likely lost to deep time, molecular remnants may persist in extant biological RNA. Identification or reconstruction of riboreplisome-like molecules could advance both origin-of-life research and synthetic biology applications.
The RNA World is the theory that life on Earth originated as RNA molecules able to both carry genetic information and catalyze enzymatic activities, without the need of DNA nor proteins. Abundant evidence supports that RNA preceded the emergence of DNA and proteins, the most notable being that both DNA replication and...
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Peter S. Shen, Derek Walsh· Journal of Virology· 0 citations
Genetic code expansion enables the site-specific installation of noncanonical amino acids (ncAAs) into proteins, but its limited efficiency in eukaryotes remains a major barrier to broader application. Here we establish a visual, plug-and-play screening platform to evolve 18S ribosomal DNA in Saccharomyces cerevisiae a...
Xiao-Xu Chen, Wentao Shen, Xian-Qing Chen et al.· Synthetic and Systems Biotec...· 0 citations
Protein evolution is a walk in the evolutionary space directed by mutation and selection. While functional and structural constraints serve as the main determinant of amino acid substitution in most proteins, synthesis cost and mutational bias can also alter the direction and rate of amino acid evolution, especially in...
A new machine-learning framework aims to improve the success rate of computational protein design while moving away from results that reproduce sequences found in nature.