The genetic code is not optimized for resource conservation

Shenhav and Zeevi conclude in a recent article (Science 370:683-687) that the universal genetic code (UGC) is optimized for resource conservation because mutations are less likely to increase proteomic nitrogen and carbon uses under the UGC than under random genetic codes (RGCs). Their finding results from miscalculating mutational effects and benchmarking against biased RGCs. Our reanalysis refutes their conclusion.

Characterization and Incidence of the First Member of the Genus Mitovirus Identified in the Phytopathogenic Species Fusarium oxysporum

A novel mycovirus named Fusarium oxysporum f. sp. dianthi mitovirus 1 (FodMV1) has been identified infecting a strain of Fusarium oxysporum f. sp. dianthi from Colombia. The genome of FodMV1 is 2313 nt long, and comprises a 172-nt 5’-UTR, a 2025-nt single ORF encoding an RdRp of 675 amino acid residues, and a 113-nt 3´-UTR. Homology BlastX searches identifies FodMV1 as a novel member of the genus Mitovirus in the family Narnaviridae. As the rest of mitoviruses, the genome of FodMV1 presents a high percentage of A+U (58.8%) and contains a number of UGA codons that encode the amino acid tryptophan rather than acting as stop codons as in the universal genetic code. Another common feature with other mitoviruses is that the 5′- and 3′-UTR regions of FodMV1 can be folded into potentially stable stem-loop structures. Result from phylogenetic analysis place FodMV1 in a different clade than the rest of mitoviruses described in other Fusarium spp. Incidence of FodMV1-infections in the collection of F. oxysporum f. sp. dianthi isolates analyzed is relatively high. Of particular interest is the fact that FodMV1 has been detected infecting isolates from two geographical areas as distant as Spain and Colombia.

Frameshifting preserves key physicochemical properties of proteins

Frameshifts in protein coding sequences are widely perceived as resulting in either nonfunctional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that, in contrast, several key physicochemical properties of protein sequences exhibit significant robustness against +1 and −1 frameshifts. In particular, we show that hydrophobicity profiles of many protein sequences remain largely invariant upon frameshifting. For example, over 2,900 human proteins exhibit a Pearson’s correlation coefficient R between the hydrophobicity profiles of the original and the +1-frameshifted variants greater than 0.7, despite an average sequence identity between the two of only 6.5% in this group. We observe a similar effect for protein sequence profiles of affinity for certain nucleobases as well as protein sequence profiles of intrinsic disorder. Finally, analysis of significance and optimality demonstrates that frameshift stability is embedded in the structure of the universal genetic code and may have contributed to shaping it. Our results suggest that frameshifting may be a powerful evolutionary mechanism for creating new proteins with vastly different sequences, yet similar physicochemical properties to the proteins from which they originate.

On Bioquantum State Systems, The Study of Algebraic Ecology and Macrocellular Biology

This dissertation is a rigorous study of ecology and macrocellular biology as a subfield of abstract algebra. We begin with the creation of an axiomatic paradigm, then move onto constructing a universal genetic code of biology. We use this to define increasingly complex algebraic structures (ecosystem, evolving populations, etc.). We prove a variety of theorems regarding to the members of the previous mathematical constructs, notably the following three: 1. There is one unique phenotypic representation of each organism. For example, if you subdivide any piece of genetic code into its phenotypic components, then two identical organisms have identical decomposed DNA 2. There are a finite number of indivisible phenotypic traits. 3. The three sophioid-definitions are equivalent: (a) dynamical evolutionary enlargement of the medial temporal lobe and frontal lobe, (b) reliance upon intelligence, (c) the existence of an intellectually- or socially-hierarchical society. Much has yet to be done on this work, but as a first draft, it stands as a jumping point for future exploits; I am working on an entirely revised second draft.

Protein 0th-Order Structure: The Key for Creating Entirely New Gene/Protein

Understanding the mechanism, how entirely new (EntNew) gene/protein or the first ancestral gene/protein of a family was created, should be one of the most important issues in the biological sciences. However, the mechanism is totally unknown still now. On the other hand, it is well known that mature protein is generally rigid and one catalytic center exists on the protein. Creation of such a mature EntNew gene/protein should be, of course, carried out through random process, because it cannot be designed in advance. However, the EntNew gene/protein never be created by random polymerization of the respective monomeric units, because of the extraordinary large sequence diversities of ~10180 and ~10130, respectively. Protein 0th-order structure or a specific amino acid composition, in which immature but water-soluble protein can be produced even through random process, holds the key for solving the difficult problem. As it was fragmentally described in the previous papers how and where EntNew gene/protein was created, I describe in detail in this review three processes generating EntNew gene/protein with some flexibility under three genetic codes, the universal genetic code, SNS primitive code and GNC primeval code, and discuss why the mature gene/protein could be created through the processes.

Probability of Change in Life: amino acid changes in single nucleotide substitutions

ABSTRACTMutations underpin the processes in life, be it beneficial or detrimental. While mutations are assumed to be random in the bereft of selection pressures, the genetic code has underlying computable probabilities in amino acid phenotypic changes. With a wide range of implications including drug resistance, understanding amino acid changes is important. In this study, we calculated the probabilities of substitutions mutations in the genetic code leading to the 20 amino acids and stop codons. Our calculations reveal an enigmatic in-built self-preserving organization of the genetic code that averts disruptive changes at the physicochemical properties level. These changes include changes to start, aromatic, negative charged amino acids and stop codons. Our findings thus reveal a statistical mechanism governing the relationship between amino acids and the universal genetic code.

Invariants of Frameshifted Variants

Frameshifts in protein coding sequences are widely perceived as resulting in either non-functional or even deleterious protein products. Indeed, frameshifts typically lead to markedly altered protein sequences and premature stop codons. By analyzing complete proteomes from all three domains of life, we demonstrate that, in contrast, several key physicochemical properties of protein sequences exhibit significant robustness against +1 and −1 frameshifts in their mRNA coding sequences. In particular, we show that hydrophobicity profiles of many protein sequences remain largely invariant upon frameshifting. For example, over 2900 human proteins exhibit a Pearson correlation coefficient between the hydrophobicity profiles of the original and the +1-frameshifted variants greater than 0.7, despite a median sequence identity between the two of only 6.5% in this group. We observe a similar effect for protein sequence profiles of affinity for certain nucleobases, their matching with the cognate mRNA nucleobase-density profiles as well as protein sequence profiles of intrinsic disorder. Finally, we show that frameshift invariance is directly embedded in the structure of the universal genetic code and may have contributed to shaping it. Our results suggest that frameshifting may be a powerful evolutionary mechanism for creating new proteins with vastly different sequences, yet similar physicochemical properties to the proteins they originate from.Significance StatementGenetic information stored in DNA is transcribed to messenger RNAs and then read in the process of translation to produce proteins. A frameshift in the reading frame at any stage of the process typically results in a significantly different protein sequence being produced and is generally assumed to be a source of detrimental errors that biological systems need to control. Here, we show that several essential properties of many protein sequences, such as their hydrophobicity profiles, remain largely unchanged upon frameshifts. This finding suggests that frameshifting could be an effective evolutionary strategy for generating novel protein sequences, which retain the functionally relevant physicochemical properties of the sequences they derive from.

The Origin of Prebiotic Information System in the Peptide/RNA World: A Simulation Model of the Evolution of Translation and the Genetic Code

Information is the currency of life, but the origin of prebiotic information remains a mystery. We propose transitional pathways from the cosmic building blocks of life to the complex prebiotic organic chemistry that led to the origin of information systems. The prebiotic information system, specifically the genetic code, is segregated, linear, and digital, and it appeared before the emergence of DNA. In the peptide/RNA world, lipid membranes randomly encapsulated amino acids, RNA, and peptide molecules, which are drawn from the prebiotic soup, to initiate a molecular symbiosis inside the protocells. This endosymbiosis led to the hierarchical emergence of several requisite components of the translation machine: transfer RNAs (tRNAs), aminoacyl-tRNA synthetase (aaRS), messenger RNAs (mRNAs), ribosomes, and various enzymes. When assembled in the right order, the translation machine created proteins, a process that transferred information from mRNAs to assemble amino acids into polypeptide chains. This was the beginning of the prebiotic <i>information</i> age. The origin of the genetic code is enigmatic; herein, we propose an evolutionary explanation: the demand for a wide range of protein enzymes over peptides in the prebiotic reactions was the main selective pressure for the origin of information-directed protein synthesis. The molecular basis of the genetic code manifests itself in the interaction of aaRS and their cognate tRNAs. In the beginning, aminoacylated ribozymes used amino acids as a cofactor with the help of bridge peptides as a process for selection between amino acids and their cognate codons/anticodons. This process selects amino acids and RNA species for the next steps. The ribozymes would give rise to pre-tRNA and the bridge peptides to pre-aaRS. Later, variants would appear and evolution would produce different but specific aaRS-tRNA-amino acid combinations. Pre-tRNA designed and built pre-mRNA for the storage of information regarding its cognate amino acid. Each pre-mRNA strand became the storage device for the genetic information that encoded the amino acid sequences in triplet nucleotides. As information appeared in the digital languages of the codon within pre-mRNA and mRNA, and the genetic code for protein synthesis evolved, the prebiotic chemistry then became more organized and directional with the emergence of the translation and genetic code. The genetic code developed in three stages that are coincident with the refinement of the translation machines: the GNC code that was developed by the pre-tRNA/pre-aaRS /pre-mRNA machine, SNS code by the tRNA/aaRS/mRNA machine, and finally the universal genetic code by the tRNA/aaRS/mRNA/ribosome machine. We suggest the coevolution of translation machines and the genetic code. The emergence of the translation machines was the beginning of the Darwinian evolution, an interplay between information and its supporting structure. Our hypothesis provides the logical and incremental steps for the origin of the programmed protein synthesis. In order to better understand the prebiotic information system, we converted letter codons into numerical codons in the Universal Genetic Code Table. We have developed a software, called CATI (Codon-Amino Acid-Translator-Imitator), to translate randomly chosen numerical codons into corresponding amino acids and vice versa. This conversion has granted us insight into how the genetic code might have evolved in the peptide/RNA world. There is great potential in the application of numerical codons to bioinformatics, such as barcoding, DNA mining, or DNA fingerprinting. We constructed the likely biochemical pathways for the origin of translation and the genetic code using the Model-View-Controller (MVC) software framework, and the translation machinery step-by-step. While using AnyLogic software, we were able to simulate and visualize the entire evolution of the translation machines, amino acids, and the genetic code.