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Register a new userThe Meccano of life
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Authors
Pierre Zofel
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This article is interested in the origin of the genetic code, it puts forward a scenario of a simultaneous selection of the bases and amino acids and setting up of a correlation between them. Each amino acid is associated with a pair of its own kind, called the binding pair and each binding pair is associated with the codon(s) corresponding to the same amino acid. An explanation is also proposed about the origin of the start and stop codons.
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The ongoing effort to detect and characterize physical entanglement in biopolymers has so far established that knots are present in many globular proteins and also abound in viral DNA packaged inside bacteriophages. RNA molecules, on the other hand, have not yet been systematically screened for the occurrence of physical knots. We have accordingly undertaken the systematic profiling of the ~6,000 RNA structures present in the protein data bank. The search identified no more than three deeply-knotted RNA molecules. These are ribosomal RNAs solved by cryo-em and consist of about 3,000 nucleotides. Compared to the case of proteins and viral DNA, the observed incidence of RNA knots is therefore practically negligible. This suggests that either evolutionary selection, or thermodynamic and kinetic folding mechanisms act towards minimizing the entanglement of RNA to an extent that is unparalleled by other types of biomolecules. The properties of the three observed RNA knotting patterns provide valuable clues for designing RNA sequences capable of self-tying in a twist-knot fold.
The mechanical properties of DNA play a critical role in many biological functions. For example, DNA packing in viruses involves confining the viral genome in a volume (the viral capsid) with dimensions that are comparable to the DNA persistence length. Similarly, eukaryotic DNA is packed in DNA-protein complexes (nucleosomes) in which DNA is tightly bent around protein spools. DNA is also tightly bent by many proteins that regulate transcription, resulting in a variation in gene expression that is amenable to quantitative analysis. In these cases, DNA loops are formed with lengths that are comparable to or smaller than the DNA persistence length. The aim of this review is to describe the physical forces associated with tightly bent DNA in all of these settings and to explore the biological consequences of such bending, as increasingly accessible by single-molecule techniques.
Biological molecules chose one of two structurally, chiral systems which are related by reflection in a mirror. It is proposed that this choice was made, causally, by magnetically polarized and physically chiral cosmic-rays, which are known to have a large role in mutagenesis. It is shown that the cosmic rays can impose a small, but persistent, chiral bias in the rate at which they induce structural changes in simple, chiral monomers that are the building blocks of biopolymers. A much larger effect should be present with helical biopolymers, in particular, those that may have been the progenitors of RNA and DNA. It is shown that the interaction can be both electrostatic, just involving the molecular electric field, and electromagnetic, also involving a magnetic field. It is argued that this bias can lead to the emergence of a single, chiral life form over an evolutionary timescale. If this mechanism dominates, then the handedness of living systems should be universal. Experiments are proposed to assess the efficacy of this process.
Chalmers famously identified pinpointing an explanation for our subjective experience as the hard problem of consciousness. He argued that subjective experience constitutes a hard problem in the sense that its explanation will ultimately require new physical laws or principles. Here, we propose a corresponding hard problem of life as the problem of how `information can affect the world. In this essay we motivate both why the problem of information as a causal agent is central to explaining life, and why it is hard - that is, why we suspect that a full resolution of the hard problem of life will, similar to as has been proposed for the hard problem of consciousness, ultimately not be reducible to known physical principles.
We propose an alternative to the prevailing two origin of life narratives, one based on a replicator first hypothesis, and one based on a metabolism first hypothesis. Both hypotheses have known difficulties: All known evolvable molecular replicators such as RNA require complex chemical (enzymatic) machinery for the replication process. Likewise, contemporary cellular metabolisms require several enzymatically catalyzed steps, and it is difficult to identify a non-enzymatic path to their realization. We propose that there must have been precursors to both replication and metabolism that enable a form of selection to take place through action of simple chemical and physical processes. We model a concrete example of such a process, repeated sequestration of binary molecular combinations after exposure to an environment with a broad distribution of chemical components, as might be realized experimentally in in a repeated wet-dry cycle. We show that the repeated sequestration dynamics results in a selective amplification of a very small subset of molecular species present in the environment, thus providing a candidate primordial selection process.
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