Detecting genomic features under weak selective pressure: the example of codon usage in animals and plants

AbstractImproved computational modeling of protein translation rates, including better prediction of where translational slowdowns along an mRNA sequence may occur, is critical for understanding co-translational folding. Because codons within a synonymous codon group are translated at different rates, many computational translation models rely on analyzing synonymous codons. Some models rely on genome-wide codon usage bias (CUB), believing that globally rare and common codons are the most informative of slow and fast translation, respectively. Others use the CUB observed only in highly expressed genes, which should be under selective pressure to be translated efficiently (and whose CUB may therefore be more indicative of translation rates). No prior work has analyzed these models for their ability to predict translational slowdowns. Here, we evaluate five models for their association with slowly translated positions as denoted by two independent ribosome footprint (RFP) count experiments from S. cerevisiae, because RFP data is often considered as a “ground truth” for translation rates across mRNA sequences. We show that all five considered models strongly associate with the RFP data and therefore have potential for estimating translational slowdowns. However, we also show that there is a weak correlation between RFP counts for the same genes originating from independent experiments, even when their experimental conditions are similar. This raises concerns about the efficacy of using current RFP experimental data for estimating translation rates and highlights a potential advantage of using computational models to understand translation rates instead.

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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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Patient-derived cells from recurrent tumors that model the evolution of IDH-mutant glioma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa088 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Lindsey E Jones ◽

Stephanie Hilz ◽

Matthew R Grimmer ◽

Tali Mazor ◽

Chloé Najac ◽

...

Keyword(s):

Tumor Tissue ◽

Selective Pressure ◽

Phylogenetic Reconstruction ◽

Telomere Maintenance ◽

Tumor Evolution ◽

Evolutionary Stage ◽

Lower Grade ◽

Community Resources ◽

Genomic Features ◽

Cell Immortality

Abstract Background IDH-mutant lower-grade gliomas (LGGs) evolve under the selective pressure of therapy, but well-characterized patient-derived cells (PDCs) modeling evolutionary stages are lacking. IDH-mutant LGGs may develop therapeutic resistance associated with chemotherapy-driven hypermutation and malignant progression. The aim of this study was to establish and characterize PDCs, single-cell-derived PDCs (scPDCs), and xenografts (PDX) of IDH1-mutant recurrences representing distinct stages of tumor evolution. Methods We derived and validated cell cultures from IDH1-mutant recurrences of astrocytoma and oligodendroglioma. We used exome sequencing and phylogenetic reconstruction to examine the evolutionary stage represented by PDCs, scPDCs, and PDX relative to corresponding spatiotemporal tumor tissue and germline DNA. PDCs were also characterized for growth and tumor immortality phenotypes, and PDX were examined histologically. Results The integrated astrocytoma phylogeny revealed 2 independent founder clonal expansions of hypermutated (HM) cells in tumor tissue that are faithfully represented by independent PDCs. The oligodendroglioma phylogeny showed more than 4000 temozolomide-associated mutations shared among tumor samples, PDCs, scPDCs, and PDX, suggesting a shared monoclonal origin. The PDCs from both subtypes exhibited hallmarks of tumorigenesis, retention of subtype-defining genomic features, production of 2-hydroxyglutarate, and subtype-specific telomere maintenance mechanisms that confer tumor cell immortality. The oligodendroglioma PDCs formed infiltrative intracranial tumors with characteristic histology. Conclusions These PDCs, scPDCs, and PDX are unique and versatile community resources that model the heterogeneous clonal origins and functions of recurrent IDH1-mutant LGGs. The integrated phylogenies advance our knowledge of the complex evolution and immense mutational load of IDH1-mutant HM glioma.

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Experimental determination of codon usage-dependent selective pressure on high copy-number genes in Saccharomyces cerevisiae

10.1101/358259 ◽

2018 ◽

Cited By ~ 1

Author(s):

Lyne Jossé ◽

Tarun Singh ◽

Tobias von der Haar

Keyword(s):

Gene Expression ◽

Saccharomyces Cerevisiae ◽

Codon Usage ◽

Copy Number ◽

Molecular Mechanisms ◽

Selective Pressure ◽

Recombinant Protein Expression ◽

High Expression ◽

Expression Levels ◽

Optimal Codon

AbstractOne of the central hypotheses in the theory of codon usage evolution is that in highly expressed genes particular codon usage patterns arise because they facilitate efficient gene expression and are thus selected for in evolution. Here we use plasmid copy number assays and growth rate measurements to explore details of the relationship between codon usage, gene expression level, and selective pressure in Saccharomyces cerevisiae. We find that when high expression levels are required optimal codon usage is beneficial and provides a fitness advantage, consistent with evolutionary theory. However, when high expression levels are not required, optimal codon usage is surprisingly and strongly selected against. We show that this selection acts at the level of protein synthesis, and we exclude a number of molecular mechanisms as the source for this negative selective pressure including nutrient and ribosome limitations and proteotoxicity effects. These findings inform our understanding of the evolution of codon usage bias, as well as the design of recombinant protein expression systems.

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Selective pressure dominates the synonymous codon usage in parvoviridae

Virus Genes ◽

10.1007/s11262-012-0818-6 ◽

2012 ◽

Vol 46 (1) ◽

pp. 10-19 ◽

Cited By ~ 21

Author(s):

Sheng-Lin Shi ◽

Yi-Ren Jiang ◽

Yan-Qun Liu ◽

Run-Xi Xia ◽

Li Qin

Keyword(s):

Codon Usage ◽

Selective Pressure ◽

Synonymous Codon ◽

Synonymous Codon Usage

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Splicing buffers suboptimal codon usage in human cells

10.1101/527440 ◽

2019 ◽

Author(s):

Christine Mordstein ◽

Rosina Savisaar ◽

Robert S Young ◽

Jeanne Bazile ◽

Lana Talmane ◽

...

Keyword(s):

Codon Usage ◽

Human Genome ◽

Selective Pressure ◽

Gc Content ◽

Nucleotide Composition ◽

Mrna Splicing ◽

Mrna Levels ◽

Cytoplasmic Localization ◽

Protein Coding ◽

Positive Effect

Although multiple studies have addressed the effects of codon usage on gene expression, such studies were typically performed in unspliced model genes. In the human genome, most genes undergo splicing and patterns of codon usage are splicing-dependent: guanine and cytosine (GC) content is highest within single-exon genes and within first exons of multi-exon genes. Intrigued by this observation, we measured the effects of splicing on expression in a panel of synonymous variants of GFP and mKate2 reporter genes that varied in nucleotide composition. We found that splicing promotes the expression of adenine and thymine (AT)-rich variants by increasing their steady-state protein and mRNA levels, in part through promoting cytoplasmic localization of mRNA. Splicing had little or no effect on the expression of GC-rich variants. In the absence of splicing, high GC content at the 5' end, but not at the 3' end of the coding sequence positively correlated with expression. Among endogenous human protein-coding transcripts, GC content has a more positive effect on various expression measures of unspliced, relative to spliced mRNAs. We propose that splicing promotes the expression of AT-rich genes, leading to selective pressure for the retention of introns in the human genome.

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Evolutionary analysis of LP3 gene family in conifers: an ASR homolog

10.1101/2020.03.27.011197 ◽

2020 ◽

Author(s):

Jonathan Lecoy ◽

MR García-Gil

Keyword(s):

Codon Usage ◽

Gene Family ◽

Loblolly Pine ◽

Molecular Mechanisms ◽

Selective Pressure ◽

Phylogenetic Analyses ◽

Acid Stress ◽

Water Deficit Stress ◽

Evolutionary Analysis ◽

Translation Efficiency

AbstractDrought has long been established as a major environmental stress for plants which have in turn developed several coping strategies, ranging from physiological to molecular mechanisms. LP3; a homolog of the Abscisic Acid, Stress and Ripening (ASR) gene was first detected in tomato; and has been shown to be present in four different isoforms in loblolly pine called LP3-0, LP3-1, LP3-2 and LP3-3. While ASR has already been extensively studied notably in tomato, the same cannot be said of LP3. Like ASR, the different LP3 isoforms have been shown to be upregulated in response to water deficit stress and to also act as transcription factors for genes likely involved in hexose transport. In this study we have investigated the evolutionary history of LP3 gene family, with the aim of relating it to that of ASR from a phylogenetic perspective and comparing the differences in selective pressure and codon usage. Phylogenetic analyses of different LP3 homologs compared to ASR show that LP3 is less divergent across species than ASR and that even when comparing the different sub-sections of the gene the divergence rate of LP3 is lower than that of ASR. Analysis of different gene parameters showed that there were differences in GC1% and GC2% but not in total or GC3% content. All genes had a relatively high CAI value associated with a low to moderate ENC value, which is indicative of high translation efficiency found in highly expressed genes. Analysis of codon usage also showed that LP3 preferentially uses different codons than ASR. Selective pressure analysis across most of the LP3 and ASR genes used in this study showed that these genes were principally undergoing purifying selection, with the exception of LP3-3 which seems to be undergoing diversifying selection most probably due to the fact that it likely recently diverged from LP3-0. This study thus provides insight in how ASR and LP3 have diverged from each other while remaining homologous.

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Experimental determination of codon usage‐dependent selective pressure on high copy‐number genes in Saccharomyces cerevisiae

Yeast ◽

10.1002/yea.3373 ◽

2018 ◽

Author(s):

Lyne Jossé ◽

Tarun Singh ◽

Tobias Haar

Keyword(s):

Saccharomyces Cerevisiae ◽

Codon Usage ◽

Experimental Determination ◽

Copy Number ◽

Selective Pressure ◽

High Copy Number

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Differences in Codon Usage Bias between Photosynthesis-Related Genes and Genetic System-Related Genes of Chloroplast Genomes in Cultivated and Wild Solanum Species

International Journal of Molecular Sciences ◽

10.3390/ijms19103142 ◽

2018 ◽

Vol 19 (10) ◽

pp. 3142 ◽

Cited By ~ 10

Author(s):

Ruizhi Zhang ◽

Li Zhang ◽

Wei Wang ◽

Zhu Zhang ◽

Huihui Du ◽

...

Keyword(s):

Gene Expression ◽

Codon Usage ◽

Codon Usage Bias ◽

Selective Pressure ◽

Genetic System ◽

Solanum Species ◽

Wild Relatives ◽

Mutational Bias ◽

The Third ◽

Chloroplast Genomes

Solanum is one of the largest genera, including two important crops—potato (Solanum tuberosum) and tomato (Solanum lycopersicum). In this study we compared the chloroplast codon usage bias (CUB) among 12 Solanum species, between photosynthesis-related genes (Photo-genes) and genetic system-related genes (Genet-genes), and between cultivated species and wild relatives. The Photo-genes encode proteins for photosystems, the photosynthetic electron transport chain, and RuBisCO, while the Genet-genes encode proteins for ribosomal subunits, RNA polymerases, and maturases. The following findings about the Solanum chloroplast genome CUB were obtained: (1) the nucleotide composition, gene expression, and selective pressure are identified as the main factors affecting chloroplast CUB; (2) all these 12 chloroplast genomes prefer A/U over G/C and pyrimidines over purines at the third-base of codons; (3) Photo-genes have higher codon adaptation indexes than Genet-genes, indicative of a higher gene expression level and a stronger adaptation of Photo-genes; (4) gene function is the primary factor affecting CUB of Photo-genes but not Genet-genes; (5) Photo-genes prefer pyrimidine over purine, whereas Genet-genes favor purine over pyrimidine, at the third position of codons; (6) Photo-genes are mainly affected by the selective pressure, whereas Genet-genes are under the underlying mutational bias; (7) S. tuberosum is more similar with Solanum commersonii than with Solanum bulbocastanum; (8) S. lycopersicum is greatly different from the analyzed seven wild relatives; (9) the CUB in codons for valine, aspartic acid, and threonine are the same between the two crop species, S. tuberosum and S. lycopersicum. These findings suggest that the chloroplast CUB contributed to the differential requirement of gene expression activity and function between Photo-genes and Genet-genes and to the performance of cultivated potato and tomato.

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