The 3-Base Periodicity and Codon Usage of Coding Sequences Are Correlated with Gene Expression at the Level of Transcription Elongation

Abstract Codon Usage Preferences (CUPrefs) describe the unequal usage of synonymous codons at the gene, chromosome, or genome levels. Numerous indices have been developed to evaluate CUPrefs, either in absolute terms or with respect to a reference. We introduce the normalized index COUSIN (for COdon Usage Similarity INdex), that compares the CUPrefs of a query against those of a reference and normalizes the output over a Null Hypothesis of random codon usage. The added value of COUSIN is to be easily interpreted, both quantitatively and qualitatively. An eponymous software written in Python3 is available for local or online use (http://cousin.ird.fr). This software allows for an easy and complete analysis of CUPrefs via COUSIN, includes seven other indices, and provides additional features such as statistical analyses, clustering, and CUPrefs optimization for gene expression. We illustrate the flexibility of COUSIN and highlight its advantages by analyzing the complete coding sequences of eight divergent genomes. Strikingly, COUSIN captures a bimodal distribution in the CUPrefs of human and chicken genes hitherto unreported with such precision. COUSIN opens new perspectives to uncover CUPrefs specificities in genomes in a practical, informative, and user-friendly way.

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Codon Usage Bias Prefers AT Bases in Coding Sequences Among the Essential Genes of Haemophilus influenzae

Notulae Scientia Biologicae ◽

10.15835/nsb649386 ◽

2014 ◽

Vol 6 (4) ◽

pp. 417-421 ◽

Cited By ~ 2

Author(s):

Chakraborty SUPRIYO ◽

Paul PROSENJIT ◽

Tarikul Huda MAZUMDER

Keyword(s):

Gene Expression ◽

Haemophilus Influenzae ◽

Codon Usage ◽

Codon Usage Bias ◽

Compositional Analysis ◽

Revealed Preference ◽

Nucleotide Composition ◽

Essential Genes ◽

Coding Sequences ◽

Codon Positions

The base composition at three different codon positions in relation to codon usagebias and gene expressivity was studied in a sample of twenty five essential genes from Haemophilus influenzae. ENC, CBI and Fop were used to quantify the variation in codon usage bias for the cds. CAI is used to estimate the level of gene expression of the cds selected in the present study. To find out the relationship between the extent of codon bias and nucleotide composition the values of A, T, G, C and GC they were compared with the A3, T3, G3, C3 and GC3 values, respectively. The results showed relatively weak codon usage bias among the coding sequences (cds) of Haemophilus influenzae. This in turn, implies that the essential genes prefer to use a set of restricted codons. However, the base compositional analysis of essential genes in Haemophilus influenzae revealed preference of AT to GC bases within their coding sequences and this preference might affect gene expression as indicated by the relatively high CAI values ofthe coding sequences.

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Linking transcription, RNA polymerase II elongation and alternative splicing

Biochemical Journal ◽

10.1042/bcj20200475 ◽

2020 ◽

Vol 477 (16) ◽

pp. 3091-3104 ◽

Cited By ~ 1

Author(s):

Luciana E. Giono ◽

Alberto R. Kornblihtt

Keyword(s):

Gene Expression ◽

Alternative Splicing ◽

Rna Polymerase Ii ◽

Environmental Changes ◽

Transcription Elongation ◽

Single Gene ◽

Regulation Of Gene Expression ◽

Regulation Of Transcription ◽

Stepping Stones ◽

Eukaryotic Transcription

Gene expression is an intricately regulated process that is at the basis of cell differentiation, the maintenance of cell identity and the cellular responses to environmental changes. Alternative splicing, the process by which multiple functionally distinct transcripts are generated from a single gene, is one of the main mechanisms that contribute to expand the coding capacity of genomes and help explain the level of complexity achieved by higher organisms. Eukaryotic transcription is subject to multiple layers of regulation both intrinsic — such as promoter structure — and dynamic, allowing the cell to respond to internal and external signals. Similarly, alternative splicing choices are affected by all of these aspects, mainly through the regulation of transcription elongation, making it a regulatory knob on a par with the regulation of gene expression levels. This review aims to recapitulate some of the history and stepping-stones that led to the paradigms held today about transcription and splicing regulation, with major focus on transcription elongation and its effect on alternative splicing.

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Massively parallel gene expression variation measurement of a synonymous codon library

BMC Genomics ◽

10.1186/s12864-021-07462-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Alexander Schmitz ◽

Fuzhong Zhang

Keyword(s):

Gene Expression ◽

Codon Usage ◽

Single Cells ◽

Massively Parallel ◽

Protein Abundance ◽

Translation Efficiency ◽

Gene Expression Variation ◽

Expression Variation ◽

Change In Mean ◽

Adaptation Index

Abstract Background Cell-to-cell variation in gene expression strongly affects population behavior and is key to multiple biological processes. While codon usage is known to affect ensemble gene expression, how codon usage influences variation in gene expression between single cells is not well understood. Results Here, we used a Sort-seq based massively parallel strategy to quantify gene expression variation from a green fluorescent protein (GFP) library containing synonymous codons in Escherichia coli. We found that sequences containing codons with higher tRNA Adaptation Index (TAI) scores, and higher codon adaptation index (CAI) scores, have higher GFP variance. This trend is not observed for codons with high Normalized Translation Efficiency Index (nTE) scores nor from the free energy of folding of the mRNA secondary structure. GFP noise, or squared coefficient of variance (CV2), scales with mean protein abundance for low-abundant proteins but does not change at high mean protein abundance. Conclusions Our results suggest that the main source of noise for high-abundance proteins is likely not originating at translation elongation. Additionally, the drastic change in mean protein abundance with small changes in protein noise seen from our library implies that codon optimization can be performed without concerning gene expression noise for biotechnology applications.

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Prediction of gene expression under drought stress in spring wheat using codon usage pattern

Saudi Journal of Biological Sciences ◽

10.1016/j.sjbs.2021.04.015 ◽

2021 ◽

Author(s):

Meshal M. Almutairi ◽

Abdullah A. Alrajhi

Keyword(s):

Gene Expression ◽

Drought Stress ◽

Codon Usage ◽

Spring Wheat ◽

Codon Usage Pattern ◽

Usage Pattern

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Evolutionary Patterns of Sex-Biased Genes in Three Species of Haplodiploid Insects

Insects ◽

10.3390/insects11060326 ◽

2020 ◽

Vol 11 (6) ◽

pp. 326

Author(s):

Yu-Jun Wang ◽

Hua-Ling Wang ◽

Xiao-Wei Wang ◽

Shu-Sheng Liu

Keyword(s):

Gene Expression ◽

Slow Rate ◽

Species Complex ◽

Evolutionary Patterns ◽

Protein Coding ◽

Coding Sequences ◽

Species Comparisons ◽

Differential Gene ◽

Males And Females ◽

And Behavior

Females and males often differ obviously in morphology and behavior, and the differences between sexes are the result of natural selection and/or sexual selection. To a great extent, the differences between the two sexes are the result of differential gene expression. In haplodiploid insects, this phenomenon is obvious, since males develop from unfertilized zygotes and females develop from fertilized zygotes. Whiteflies of the Bemisia tabaci species complex are typical haplodiploid insects, and some species of this complex are important pests of many crops worldwide. Here, we report the transcriptome profiles of males and females in three species of this whitefly complex. Between-species comparisons revealed that non-sex-biased genes display higher variation than male-biased or female-biased genes. Sex-biased genes evolve at a slow rate in protein coding sequences and gene expression and have a pattern of evolution that differs from those of social haplodiploid insects and diploid animals. Genes with high evolutionary rates are more related to non-sex-biased traits—such as nutrition, immune system, and detoxification—than to sex-biased traits, indicating that the evolution of protein coding sequences and gene expression has been mainly driven by non-sex-biased traits.

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A and T homopolymeric stretches mediate a DNA inversion in Plasmodium falciparum which results in loss of gene expression

Molecular and Cellular Biology ◽

10.1128/mcb.10.6.3243-3246.1990 ◽

1990 ◽

Vol 10 (6) ◽

pp. 3243-3246

Author(s):

L G Pologe ◽

D de Bruin ◽

J V Ravetch

Keyword(s):

Gene Expression ◽

Plasmodium Falciparum ◽

Gene Structure ◽

Infected Erythrocyte ◽

Dna Rearrangement ◽

Coding Sequences ◽

Dna Inversion ◽

Erythrocyte Surface ◽

Stable Substrate ◽

Flanking Sequences

Ring-infected erythrocyte surface antigen-negative isolates of Plasmodium falciparum demonstrate a complex DNA rearrangement with inversion of 5' coding sequences, deletion of upstream and flanking sequences, and healing of the truncated chromosome by telomere addition. An inversion intermediate that results in the telomeric gene structure for RESA has been identified in the pathway. This inversion creates a mitotically stable substrate for the sequence-specific addition of telomere repeats at the deletion breakpoint.

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Codon replacement in the PGK1 gene of Saccharomyces cerevisiae: experimental approach to study the role of biased codon usage in gene expression

Molecular and Cellular Biology ◽

10.1128/mcb.7.8.2914-2924.1987 ◽

1987 ◽

Vol 7 (8) ◽

pp. 2914-2924

Author(s):

A Hoekema ◽

R A Kastelein ◽

M Vasser ◽

H A de Boer

Keyword(s):

Gene Expression ◽

Saccharomyces Cerevisiae ◽

Steady State ◽

Codon Usage ◽

Experimental Approach ◽

Mrna Translation ◽

Yeast Cells ◽

Expression Level ◽

Start Codon ◽

Mrna Levels

The coding sequences of genes in the yeast Saccharomyces cerevisiae show a preference for 25 of the 61 possible coding triplets. The degree of this biased codon usage in each gene is positively correlated to its expression level. Highly expressed genes use these 25 major codons almost exclusively. As an experimental approach to studying biased codon usage and its possible role in modulating gene expression, systematic codon replacements were carried out in the highly expressed PGK1 gene. The expression of phosphoglycerate kinase (PGK) was studied both on a high-copy-number plasmid and as a single copy gene integrated into the chromosome. Replacing an increasing number (up to 39% of all codons) of major codons with synonymous minor ones at the 5' end of the coding sequence caused a dramatic decline of the expression level. The PGK protein levels dropped 10-fold. The steady-state mRNA levels also declined, but to a lesser extent (threefold). Our data indicate that this reduction in mRNA levels was due to destabilization caused by impaired translation elongation at the minor codons. By preventing translation of the PGK mRNAs by the introduction of a stop codon 3' and adjacent to the start codon, the steady-state mRNA levels decreased dramatically. We conclude that efficient mRNA translation is required for maintaining mRNA stability in S. cerevisiae. These findings have important implications for the study of the expression of heterologous genes in yeast cells.

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Identification of a regulatory region that mediates glucose-dependent induction of the Saccharomyces cerevisiae enolase gene ENO2

Molecular and Cellular Biology ◽

10.1128/mcb.6.7.2287-2297.1986 ◽

1986 ◽

Vol 6 (7) ◽

pp. 2287-2297

Author(s):

R Cohen ◽

J P Holland ◽

T Yokoi ◽

M J Holland

Keyword(s):

Gene Expression ◽

Regulatory Region ◽

Carbon Sources ◽

Initiation Site ◽

Deletion Mapping ◽

Regulatory Regions ◽

Coding Sequences ◽

Flanking Region ◽

Fused Gene ◽

In Cells

There are two yeast enolase genes, designated ENO1 and ENO2, which are expressed differentially in vegetative cells grown on glucose and in cells grown on gluconeogenic carbon sources. ENO2 is induced more than 20-fold in cells grown on glucose, whereas ENO1 expression is similar in cells grown on glucose and in cells grown on gluconeogenic carbon sources. Sequences within the 5' flanking region of ENO2 which are required for glucose-dependent induction were identified by deletion mapping analysis. These studies were carried out by using a fused gene containing the ENO2 5' flanking sequences and the ENO1 coding sequences. This fused gene undergoes glucose-dependent induction and is expressed at the same level as the resident ENO2 gene in cells grown on glucose or gluconeogenic carbon sources. Expression of fused genes containing deletion mutations within the ENO2 5' flanking region was monitored after integration at the ENO1 locus of a strain carrying a deletion of the resident ENO1 coding sequences. This analysis showed that there are two upstream activation sites located immediately upstream and downstream from a position 461 base pairs upstream from the transcriptional initiation site. Either one of these upstream activation sites is sufficient for glucose-dependent induction and normal gene expression in the presence of gluconeogenic carbon sources. Deletion of both regulatory regions results in a complete loss of gene expression. The regulatory regions function normally in both orientations relative to the coding sequences. Mutant fused genes containing small deletions within the regulatory regions were constructed; these genes were expressed normally in gluconeogenic carbon sources but were not induced in the presence of glucose. Based on this analysis, ENO2 contains a cis-acting regulatory region which is required for gene expression and mediates glucose-dependent induction of gene expression.

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