Codon usage vis-a-vis start and stop codon context analysis of three dicot species

The design of Pfizer/BioNTech and Moderna mRNA vaccines involves many different types of optimizations. Proper optimization of vaccine mRNA can reduce dosage required for each injection leading to more efficient immunization programs. The mRNA components of the vaccine need to have a 5’-UTR to load ribosomes efficiently onto the mRNA for translation initiation, optimized codon usage for efficient translation elongation, and optimal stop codon for efficient translation termination. Both 5’-UTR and the downstream 3’-UTR should be optimized for mRNA stability. The replacement of uridine by N1-methylpseudourinine () complicates some of these optimization processes because is more versatile in wobbling than U. Different optimizations can conflict with each other, and compromises would need to be made. I highlight the similarities and differences between Pfizer/BioNTech and Moderna mRNA vaccines and discuss the advantage and disadvantage of each to facilitate future vaccine improvement. In particular, I point out a few optimizations in the design of the two mRNA vaccines that have not been performed properly.

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The functional readthrough extension of malate dehydrogenase reveals a modification of the genetic code

Open Biology ◽

10.1098/rsob.160246 ◽

2016 ◽

Vol 6 (11) ◽

pp. 160246 ◽

Cited By ~ 15

Author(s):

Julia Hofhuis ◽

Fabian Schueren ◽

Christopher Nötzel ◽

Thomas Lingner ◽

Jutta Gärtner ◽

...

Keyword(s):

Malate Dehydrogenase ◽

Stop Codon ◽

Protein Isoforms ◽

Translational Readthrough ◽

Peroxisomal Targeting ◽

Codon Context ◽

Targeting Signal ◽

Stop Codon Readthrough ◽

Insight Into ◽

Actual Ratio

Translational readthrough gives rise to C-terminally extended proteins, thereby providing the cell with new protein isoforms. These may have different properties from the parental proteins if the extensions contain functional domains. While for most genes amino acid incorporation at the stop codon is far lower than 0.1%, about 4% of malate dehydrogenase (MDH1) is physiologically extended by translational readthrough and the actual ratio of MDH1x (e x tended protein) to ‘normal' MDH1 is dependent on the cell type. In human cells, arginine and tryptophan are co-encoded by the MDH1x UGA stop codon. Readthrough is controlled by the 7-nucleotide high-readthrough stop codon context without contribution of the subsequent 50 nucleotides encoding the extension. All vertebrate MDH1x is directed to peroxisomes via a hidden peroxisomal targeting signal (PTS) in the readthrough extension, which is more highly conserved than the extension of lactate dehydrogenase B. The hidden PTS of non-mammalian MDH1x evolved to be more efficient than the PTS of mammalian MDH1x. These results provide insight into the genetic and functional co-evolution of these dually localized dehydrogenases.

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Single-Cell Genomic Sequencing of Three Peritrichs (Protista, Ciliophora) Reveals Less Biased Stop Codon Usage and More Prevalent Programmed Ribosomal Frameshifting Than in Other Ciliates

Frontiers in Marine Science ◽

10.3389/fmars.2020.602323 ◽

2020 ◽

Vol 7 ◽

Author(s):

Xiao Chen ◽

Chundi Wang ◽

Bo Pan ◽

Borong Lu ◽

Chao Li ◽

...

Keyword(s):

Codon Usage ◽

Single Cell ◽

Stop Codon ◽

Genomic Data ◽

Evolutionary Strategy ◽

Genomic Sequencing ◽

Ribosomal Frameshifting ◽

Genomic Features ◽

First Time ◽

Stop Codon Reassignment

Peritrichs are one of the largest groups of ciliates with over 1,000 species described so far. However, their genomic features are largely unknown. By single-cell genomic sequencing, we acquired the genomic data of three sessilid peritrichs (Cothurnia ceramicola, Vaginicola sp., and Zoothamnium sp. 2). Using genomic data from another 53 ciliates including 14 peritrichs, we reconstructed their evolutionary relationships and confirmed genome skimming as an efficient approach for expanding sampling. In addition, we profiled the stop codon usage and programmed ribosomal frameshifting (PRF) events in peritrichs for the first time. Our analysis reveals no evidence of stop codon reassignment for peritrichs, but they have prevalent +1 or -1 PRF events. These genomic features are distinguishable from other ciliates, and our observations suggest a unique evolutionary strategy for peritrichs.

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Insights into the riddles of codon usage patterns and codon context signatures in fungal genus Puccinia , a persistent threat to global agriculture

Journal of Cellular Biochemistry ◽

10.1002/jcb.29263 ◽

2019 ◽

Vol 120 (12) ◽

pp. 19555-19566 ◽

Cited By ~ 1

Author(s):

Ayan Roy ◽

Johannes van Staden

Keyword(s):

Codon Usage ◽

Usage Patterns ◽

Codon Context ◽

Global Agriculture ◽

Fungal Genus

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Genome-wide comparative analysis of codon usage bias and codon context patterns among cyanobacterial genomes

Marine Genomics ◽

10.1016/j.margen.2016.10.001 ◽

2017 ◽

Vol 32 ◽

pp. 31-39 ◽

Cited By ~ 8

Author(s):

Ratna Prabha ◽

Dhananjaya P. Singh ◽

Swati Sinha ◽

Khurshid Ahmad ◽

Anil Rai

Keyword(s):

Comparative Analysis ◽

Codon Usage ◽

Codon Usage Bias ◽

Genome Wide ◽

Codon Context

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Codon usage and codon context bias in Xanthophyllomyces dendrorhous

BMC Genomics ◽

10.1186/s12864-015-1493-5 ◽

2015 ◽

Vol 16 (1) ◽

Cited By ~ 19

Author(s):

Marcelo Baeza ◽

Jennifer Alcaíno ◽

Salvador Barahona ◽

Dionisia Sepúlveda ◽

Víctor Cifuentes

Keyword(s):

Codon Usage ◽

Xanthophyllomyces Dendrorhous ◽

Codon Context ◽

Codon Context Bias

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Evolution of differential codon usage preferences and subfunctionalisation in paralogous genes: the showcase of polypyrimidine tract binding proteins

10.1101/2020.08.30.274191 ◽

2020 ◽

Author(s):

Jérôme Bourret ◽

Fanni Borvető ◽

Ignacio G. Bravo

Keyword(s):

Codon Usage ◽

Amino Acid Level ◽

Nucleotide Composition ◽

Polypyrimidine Tract ◽

Genomic Context ◽

Context Analysis ◽

Substitution Pattern ◽

Specific Expression ◽

Polypyrimidine Tract Binding ◽

Polypyrimidine Tract Binding Protein

AbstractGene paralogs are copies of a same gene that appear after gene or full genome duplication. Redundancy generated by gene duplication may release certain evolutionary pressures, allowing one of the copies to access novel gene functions. Here we focused on role of codon usage preferences (CUPrefs) during the evolution of the polypyrimidine tract binding protein (PTBP) splicing regulator paralogs.PTBP1-3 show high identity at the amino acid level (up to 80%), but display different nucleotide composition, divergent CUPrefs and distinct tissue-specific expression levels. Phylogenetic inference differentiates the three orthologs and suggests that the three PTBP1-3 lineages predate the basal diversification within vertebrates. We identify a distinct substitution pattern towards GC3-enriching mutations in PTBP1, with a trend for the use of common codons and for a tissue-wide expression. Genomic context analysis shows that GC3-rich nucleotide composition for PTBP1s is driven by local mutational processes. In contrast, PTBP2s are enriched in AT-ending, rare codons, and display tissue-restricted expression. Nucleotide composition and CUPrefs of PTBP2 are only partly driven by local mutational forces, and could have been shaped by selective forces. Interestingly, trends for use of UUG-Leu codon match those of AT-ending codons.Our interpretation is that a combination of mutation and selection has differentially shaped CUPrefs of PTBPs in Vertebrates: GC-enrichment of PTBP1 is linked to the strong and broad tissue-expression, while AT-enrichment of PTBP2 and PTBP3 is linked to rare CUPrefs and specialized spatio-temporal expression. Our model is compatible with a gene subfunctionalisation process by differential expression regulation associated to the evolution of specific CUPrefs.

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Comparative Analysis of Eight Mitogenomes of Bark Beetles and Their Phylogenetic Implications

Insects ◽

10.3390/insects12100949 ◽

2021 ◽

Vol 12 (10) ◽

pp. 949

Author(s):

Huicong Du ◽

Jiaxing Fang ◽

Xia Shi ◽

Sufang Zhang ◽

Fu Liu ◽

...

Keyword(s):

Codon Usage ◽

Bark Beetle ◽

Phylogenetic Relationships ◽

Bark Beetles ◽

Sequence Data ◽

Stop Codon ◽

Structural Characteristics ◽

Gene Arrangement ◽

Beetle Species ◽

Phylogenetic Implications

Many bark beetles of the subfamily Scolytinae are the most economically important insect pests of coniferous forests worldwide. In this study, we sequenced the mitochondrial genomes of eight bark beetle species, including Dendroctonus micans, Orthotomicus erosus, Polygraphus poligraphus, Dryocoetes hectographus, Ips nitidus, Ips typographus, Ips subelongatus, and Ips hauseri, to examine their structural characteristics and determine their phylogenetic relationships. We also used previously published mitochondrial genome sequence data from other Scolytinae species to identify and localize the eight species studied within the bark beetle phylogeny. Their gene arrangement matched the presumed ancestral pattern of these bark beetles. Start and stop codon usage, amino acid abundance, and the relative codon usage frequencies were conserved among bark beetles. Genetic distances between species ranged from 0.037 to 0.418, and evolutionary rates of protein-coding genes ranged from 0.07 for COI to 0.69 for ND2. Our results shed light on the phylogenetic relationships and taxonomic status of several bark beetles in the subfamily Scolytinae and highlight the need for further sequencing analyses and taxonomic revisions in additional bark beetle species.

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