Is the genetic code optimized for resource conservation?
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ABSTRACT:
SUBMITTER: Xu H
PROVIDER: S-EPMC8557414 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Selection for resource conservation can shape the coding sequences of organisms living in nutrient-limited environments. Recently, it was proposed that selection for resource conservation, specifically for nitrogen and carbon content, has also shaped the structure of the standard genetic code, such that the missense mutations the code allows tend to cause small increases in the number of nitrogen and carbon atoms in amino acids. Moreover, it was proposed that this optimization is not confounded by known optimizations of the standard genetic code, such as for polar requirement or hydropathy. We challenge these claims. We show the proposed optimization for nitrogen conservation is highly sensitive to choice of null model and the proposed optimization for carbon conservation is confounded by the known conservative nature of the standard genetic code with respect to the molecular volume of amino acids. There is therefore little evidence the standard genetic code is optimized for resource conservation. We discuss our findings in the context of null models of the standard genetic code.
| S-EPMC8557452 | biostudies-literature
Project description:The ribosomal incorporation of nonnative amino acids into polypeptides in living cells provides the opportunity to endow therapeutic proteins with unique pharmacological properties. We report here the first clinical study of a biosynthetic protein produced using an expanded genetic code. Incorporation of p-acetylphenylalanine (pAcF) at distinct locations in human growth hormone (hGH) allowed site-specific conjugation with polyethylene glycol (PEG) to produce homogeneous hGH variants. A mono-PEGylated mutant hGH modified at residue 35 demonstrated favorable pharmacodynamic properties in GH-deficient rats. Clinical studies in GH-deficient adults demonstrated efficacy and safety comparable to native human growth hormone therapy but with increased potency and reduced injection frequency. This example illustrates the utility of nonnative amino acids to optimize protein therapeutics in an analogous fashion to the use of medicinal chemistry to optimize conventional natural products, low molecular weight drugs, and peptides.
| S-EPMC3107295 | biostudies-literature
Project description:BACKGROUND: The arrangement of the amino acids in the genetic code is such that neighbouring codons are assigned to amino acids with similar physical properties. Hence, the effects of translational error are minimized with respect to randomly reshuffled codes. Further inspection reveals that it is amino acids in the same column of the code (i.e. same second base) that are similar, whereas those in the same row show no particular similarity. We propose a 'four-column' theory for the origin of the code that explains how the action of selection during the build-up of the code leads to a final code that has the observed properties. RESULTS: The theory makes the following propositions. (i) The earliest amino acids in the code were those that are easiest to synthesize non-biologically, namely Gly, Ala, Asp, Glu and Val. (ii) These amino acids are assigned to codons with G at first position. Therefore the first code may have used only these codons. (iii) The code rapidly developed into a four-column code where all codons in the same column coded for the same amino acid: NUN = Val, NCN = Ala, NAN = Asp and/or Glu, and NGN = Gly. (iv) Later amino acids were added sequentially to the code by a process of subdivision of codon blocks in which a subset of the codons assigned to an early amino acid were reassigned to a later amino acid. (v) Later amino acids were added into positions formerly occupied by amino acids with similar properties because this can occur with minimal disruption to the proteins already encoded by the earlier code. As a result, the properties of the amino acids in the final code retain a four-column pattern that is a relic of the earliest stages of code evolution. CONCLUSION: The driving force during this process is not the minimization of translational error, but positive selection for the increased diversity and functionality of the proteins that can be made with a larger amino acid alphabet. Nevertheless, the code that results is one in which translational error is minimized. We define a cost function with which we can compare the fitness of codes with varying numbers of amino acids, and a barrier function, which measures the change in cost immediately after addition of a new amino acid. We show that the barrier is positive if an amino acid is added into a column with dissimilar properties, but negative if an amino acid is added into a column with similar physical properties. Thus, natural selection favours the assignment of amino acids to the positions that they occupy in the final code.
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Project description:Nucleomorphs, the remnant nuclei of photosynthetic algae that have become endosymbionts to other eukaryotes, represent a unique example of convergent reductive genome evolution in eukaryotes, having evolved independently on two separate occasions in chlorarachniophytes and cryptophytes. The nucleomorphs of the two groups have evolved in a remarkably convergent manner, with numerous very similar features. Chief among them is the extreme reduction and compaction of nucleomorph genomes, with very small chromosomes and extremely short or even completely absent intergenic spaces. These characteristics pose a number of intriguing questions regarding the mechanisms of transcription and gene regulation in such a crowded genomic context, in particular in terms of the functioning of the histone code, which is common to almost all eukaryotes and plays a central role in chromatin biology.This study examines the sequences of nucleomorph histone proteins in order to address these issues. Remarkably, all classical transcription- and repression-related components of the histone code seem to be missing from chlorarachniophyte nucleomorphs. Cryptophyte nucleomorph histones are generally more similar to the conventional eukaryotic state; however, they also display significant deviations from the typical histone code. Based on the analysis of specific components of the code, we discuss the state of chromatin and the transcriptional machinery in these nuclei.The results presented here shed new light on the mechanisms of nucleomorph transcription and gene regulation and provide a foundation for future studies of nucleomorph chromatin and transcriptional biology.
| S-EPMC4822330 | biostudies-literature
Project description:The genetic code-the language used by cells to translate their genomes into proteins that perform many cellular functions-is highly conserved throughout natural life. Rewriting the genetic code could lead to new biological functions such as expanding protein chemistries with noncanonical amino acids (ncAAs) and genetically isolating synthetic organisms from natural organisms and viruses. It has long been possible to transiently produce proteins bearing ncAAs, but stabilizing an expanded genetic code for sustained function in vivo requires an integrated approach: creating recoded genomes and introducing new translation machinery that function together without compromising viability or clashing with endogenous pathways. In this review, we discuss design considerations and technologies for expanding the genetic code. The knowledge obtained by rewriting the genetic code will deepen our understanding of how genomes are designed and how the canonical genetic code evolved.
| S-EPMC5772603 | biostudies-literature
Project description:When using a compacted version of the "I Ching" genetic code, the number of symbols is reduced to only 8 symbolic binary constants, integrated by only three symbols, being each: either the continuous or the broken horizontal line, plus the respective one word abbreviations of their resulting amino acids, namely, between four to eight accompanying the triad of lines, giving a total set of 46 possible combinations. This study is an alternate way of file compression for the genetic code, focused in the nucleotides, while another one I explored elsewhere, was focused in the groupings of amino acids, both individually and by their codon equivalents. As an Appendix 1 & 2 analogy, I add an example of "mutations" in literature, based on two early versions of "The Fair" (in its first edition of 1963, and in its first red edition of 1971), comparing its vignettes, and written in Spanish by my professor Juan José Arreola, now at his 101 year of birth.
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Project description:Emergency resource is important for people evacuation and property rescue when accident occurs. The relief efforts could be promoted by a reasonable emergency resource allocation schedule in advance. As the marine environment is complicated and changeful, the place, type, severity of maritime accident is uncertain and stochastic, bringing about dynamic demand of emergency resource. Considering dynamic demand, how to make a reasonable emergency resource allocation schedule is challenging. The key problem is to determine the optimal stock of emergency resource for supplier centers to improve relief efforts. This paper studies the dynamic demand, and which is defined as a set. Then a maritime emergency resource allocation model with uncertain data is presented. Afterwards, a robust approach is developed and used to make sure that the resource allocation schedule performs well with dynamic demand. Finally, a case study shows that the proposed methodology is feasible in maritime emergency resource allocation. The findings could help emergency manager to schedule the emergency resource allocation more flexibly in terms of dynamic demand.
| S-EPMC5730157 | biostudies-literature
Project description:Expanding the genetic code to enable the incorporation of unnatural amino acids into proteins in biological systems provides a powerful tool for studying protein structure and function. While this technology has been mostly developed and applied in bacterial and mammalian cells, it recently expanded into animals, including worms, fruit flies, zebrafish, and mice. In this review, we highlight recent advances toward the methodology development of genetic code expansion in animal model organisms. We further illustrate the applications, including proteomic labeling in fruit flies and mice and optical control of protein function in mice and zebrafish. We summarize the challenges of unnatural amino acid mutagenesis in animals and the promising directions toward broad application of this emerging technology.
| S-EPMC7026698 | biostudies-literature
Project description:A dynamical theory for the evolution of the genetic code is presented, which accounts for its universality and optimality. The central concept is that a variety of collective, but non-Darwinian, mechanisms likely to be present in early communal life generically lead to refinement and selection of innovation-sharing protocols, such as the genetic code. Our proposal is illustrated by using a simplified computer model and placed within the context of a sequence of transitions that early life may have made, before the emergence of vertical descent.
| S-EPMC1502294 | biostudies-other
Project description:Selenocysteine (Sec) is naturally incorporated into proteins by recoding the stop codon UGA. Sec is not hardwired to UGA, as the Sec insertion machinery was found to be able to site-specifically incorporate Sec directed by 58 of the 64 codons. For 15 sense codons, complete conversion of the codon meaning from canonical amino acid (AA) to Sec was observed along with a tenfold increase in selenoprotein yield compared to Sec insertion at the three stop codons. This high-fidelity sense-codon recoding mechanism was demonstrated for Escherichia coli formate dehydrogenase and recombinant human thioredoxin reductase and confirmed by independent biochemical and biophysical methods. Although Sec insertion at UGA is known to compete against protein termination, it is surprising that the Sec machinery has the ability to outcompete abundant aminoacyl-tRNAs in decoding sense codons. The findings have implications for the process of translation and the information storage capacity of the biological cell.
| S-EPMC4004526 | biostudies-literature