`The frozen accident' as an evolutionary adaptation: A rate distortion theory perspective on the dynamics and symmetries of genetic coding mechanisms

We survey some interpretations and related issues concerning the frozen hypothesis due to F. Crick and how it can be explained in terms of several natural mechanisms involving error correction codes, spin glasses, symmetry breaking and the characteristic robustness of genetic networks. The approach to most of these questions involves using elements of Shannon's rate distortion theory incorporating a semantic system which is meaningful for the relevant alphabets and vocabulary implemented in transmission of the genetic code. We apply the fundamental homology between information source uncertainty with the free energy density of a thermodynamical system with respect to transcriptional regulators and the communication channels of sequence/structure in proteins. This leads to the suggestion that the frozen accident may have been a type of evolutionary adaptation

On the origin of the mitochondrial genetic code: Towards a unified mathematical framework for the management of genetic information

The origin of the genetic code represents one of the most challenging problems in molecular evolution. The genetic code is an important universal feature of extant organisms and indicates a common ancestry of different forms of life on earth. Known variants of the genetic code can be mainly divided in mitochondrial and nuclear classes. Here we provide a new insight on the origin of the mitochondrial genetic code: we found that its degeneracy distribution can be explained by using a mathematical approach recently developed for the description of the Euplotes nuclear variant of the genetic code. The results point to a primeval mitochondrial genetic code composed of four base codons, which we call tesserae, that, among other features, exhibit outstanding error detection capabilities. The theoretical description suggests also a formulation of a plausible biological theory about the origin of protein coding. Such theory is based on the symmetry properties of hypothetical primeval chemical adaptors between nucleic acids and amino acids (ancient tRNA’s). Our paper provides a unified mathematical framework for different hypotheses on the origin of genetic coding. Also, it contributes to revisit our present view about the evolutionary steps that led to extant genetic codes by giving a new first-principles perspective on the difficult problem of the origin of the genetic code, and consequently, on the origin of life on earth

Exon-phase symmetry and intrinsic structural disorder promote modular evolution in the human genome

A key signature of module exchange in the genome is phase symmetry of exons, suggestive of exon shuffling events that occurred without disrupting translation reading frame. At the protein level, intrinsic structural disorder may be another key element because disordered regions often serve as functional elements that can be effectively integrated into a protein structure. Therefore, we asked whether exon-phase symmetry in the human genome and structural disorder in the human proteome are connected, signalling such evolutionary mechanisms in the assembly of multi-exon genes. We found an elevated level of structural disorder of regions encoded by symmetric exons and a preferred symmetry of exons encoding for mostly disordered regions (>70% predicted disorder). Alternatively spliced symmetric exons tend to correspond to the most disordered regions. The genes of mostly disordered proteins (>70% predicted disorder) tend to be assembled from symmetric exons, which often arise by internal tandem duplications. Preponderance of certain types of short motifs (e.g. SH3-binding motif) and domains (e.g. high-mobility group domains) suggests that certain disordered modules have been particularly effective in exon-shuffling events. Our observations suggest that structural disorder has facilitated modular assembly of complex genes in evolution of the human genome. © 2013 The Author(s)

Encoding folding paths of RNA switches

RNA co-transcriptional folding has long been suspected to play an active role in helping proper native folding of ribozymes and structured regulatory motifs in mRNA untranslated regions. Yet, the underlying mechanisms and coding requirements for efficient co-transcriptional folding remain unclear. Traditional approaches have intrinsic limitations to dissect RNA folding paths, as they rely on sequence mutations or circular permutations that typically perturb both RNA folding paths and equilibrium structures. Here, we show that exploiting sequence symmetries instead of mutations can circumvent this problem by essentially decoupling folding paths from equilibrium structures of designed RNA sequences. Using bistable RNA switches with symmetrical helices conserved under sequence reversal, we demonstrate experimentally that native and transiently formed helices can guide efficient co-transcriptional folding into either long-lived structure of these RNA switches. Their folding path is controlled by the order of helix nucleations and subsequent exchanges during transcription, and may also be redirected by transient antisense interactions. Hence, transient intra- and intermolecular base pair interactions can effectively regulate the folding of nascent RNA molecules into different native structures, provided limited coding requirements, as discussed from an information theory perspective. This constitutive coupling between RNA synthesis and RNA folding regulation may have enabled the early emergence of autonomous RNA-based regulation networks.Comment: 9 pages, 6 figure