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PubMed2000

The quality of merC, a module of the mer mosaic.

We examined a region of high variability in the mosaic mercury resistance (mer) operon of natural bacterial isolates from the primate intestinal microbiota. The region between the merP and merA genes of nine mer loci was sequenced and either the merC, the merF, or no gene was present. Two novel merC genes were identified. Overall nucleotide diversity, pi (per 100 sites), of the merC gene was greater (49.63) than adjacent merP (35.82) and merA (32.58) genes. However, the consequences of this variability for the predicted structure of the MerC protein are limited and putative functional elements (metal-binding ligands and transmembrane domains) are strongly conserved. Comparison of codon usage of the merTP, merC, and merA genes suggests that several merC genes are not coeval with their flanking sequences. Although evidence of homologous recombination within the very variable merC genes is not apparent, the flanking regions have higher homologies than merC, and recombination appears to be driving their overall sequence identities higher. The synonymous codon usage bias (EN(C)) values suggest greater variability in expression of the merC gene than in flanking genes in six different bacterial hosts. We propose a model for the evolution of MerC as a host-dependent, adventitious module of the mer operon.

Amino Acid Sequence↗

PubMed1992

Computer-aided gene design.

A computer program, which runs on MS-DOS personal computers, is described that assists in the design of synthetic genes coding for proteins. The goal of the program is the design of a gene which (i) contains as many unique restriction sites as possible and (ii) uses a specific codon usage. The gene designed according to the criteria above is (i) suitable for 'modular mutagenesis' experiments and (ii) optimized for expression. The program 'reverse-translates' protein sequences into degenerated DNA sequences, generates a map of potential restriction sites and locates sequence positions where unique restriction sites can be accommodated. The nucleic acid sequence is then 'refined' according to a specific codon usage to remove any degeneration. Unique restriction sites, if potentially present, can be 'forced' into the degenerated nucleic acid sequence by using 'priority codes' assigned to different restriction sequences.

Amino Acid Sequence↗

PubMed1996

Transgenic barley expressing a protein-engineered, thermostable (1,3-1,4)-beta-glucanase during germination.

The codon usage of a hybrid bacterial gene encoding a thermostable (1,3-1,4)-beta-glucanase was modified to match that of the barley (1,3-1,4)-beta-glucanase isoenzyme EII gene. Both the modified and unmodified bacterial genes were fused to a DNA segment encoding the barley high-pI alpha-amylase signal peptide downstream of the barley (1,3-1,4)-beta-glucanase isoenzyme EII gene promoter. When introduced into barley aleurone protoplasts, the bacterial gene with adapted codon usage directed synthesis of heat stable (1,3-1,4)-beta-glucanase, whereas activity of the heterologous enzyme was not detectable when protoplasts were transfected with the unmodified gene. In a different expression plasmid, the codon modified bacterial gene was cloned downstream of the barley high-pI alpha-amylase gene promoter and signal peptide coding region. This expression cassette was introduced into immature barley embryos together with plasmids carrying the bar and the uidA genes. Green, fertile plants were regenerated and approximately 75% of grains harvested from primary transformants synthesized thermostable (1,3-1,4)-beta-glucanase during germination. All three trans genes were detected in 17 progenies from a homozygous T1 plant.

Amino Acid Sequence↗

PubMed1993

Codon preference in corynebacteria.

The codon usage (CU) of 34 genes from the closely related species, Brevibacterium lactofermentum and Corynebacterium glutamicum (BLCG), was analysed and compared with that of 23 genes from other Brevibacterium and Corynebacterium species. The G+C content of the BLCG genes ranged from 50 to 62%. A wider range was found in other corynebacterial genes (25-71%). The G+C contents of non-coding regions in glutamic acid bacteria are lower than those of the coding regions and both values are lower than the G+C content of ribosomal RNA (rRNA) sequences, suggesting an unusual biased mutation pressure. The CU and synonymous codon usage (SCU) analysis showed several common characteristics among the sequenced corynebacterial genes, consistent with the close relatedness of B. lactofermentum and C. glutamicum. A subset of 25 preferred codons were deduced from the presumably highly expressed genes and they encode most of the amino acid (aa) residues of the BLCG group. An analysis of the effective number of codons (Nc) was carried out in order to check the GC3s (G+C content at the silent third position of sense codons) dependence of the CU in corynebacteria. Nc values showed differences between the BLCG group and other corynebacterial sequences. A comparison of the most used codons for each aa showed a stronger similarity to Streptomyces than to Escherichia coli. The CU/SCU tables of corynebacteria are useful for identification of protein-coding regions, including start codons when they are uncertain, and for designing oligodeoxyribonucleotide probes from an aa sequence.

Base Sequence↗

PubMed1993

Low codon bias and high rates of synonymous substitution in Drosophila hydei and D. melanogaster histone genes.

We have evaluated codon usage bias in Drosophila histone genes and have obtained the nucleotide sequence of a 5,161-bp D. hydei histone gene repeat unit. This repeat contains genes for all five histone proteins (H1, H2a, H2b, H3, and H4) and differs from the previously reported one by a second EcoRI site. These D. hydei repeats have been aligned to each other and to the 5.0-kb (i.e., long) and 4.8-kb (i.e., short) histone repeat types from D. melanogaster. In each species, base composition at synonymous sites is similar to the average genomic composition and approaches that in the small intergenic spacers of the histone gene repeats. Accumulation of synonymous changes at synonymous sites after the species diverged is quite high. Both of these features are consistent with the relatively low codon usage bias observed in these genes when compared with other Drosophila genes. Thus, the generalization that abundantly expressed genes in Drosophila have high codon bias and low rates of silent substitution does not hold for the histone genes.

Animals↗

PubMed2001

Limitations of compositional approach to identifying horizontally transferred genes.

Genes with atypical G+C content and pattern of codon usage in a certain genome are possibly of exotic origin, and this idea has been applied to identify horizontal events. In this way, it was postulated that a total of 755 genes in the E. coli genome are relics of horizontal events after the divergence of E. coli from the Salmonella lineage 100 million years ago (Lawrence and Ochman, 1998). In this paper we propose a new way to study sequence composition more thoroughly. We found that although the 755 genes differ in composition from other genes in the E. coli genome, the difference is minor. If we accepted that these genes are horizontally transferred, then (1) it would be more likely that they were transferred from genomes evolutionarily closely related to E. coli; but (2) the dating method used by Lawrence and Ochman (1997, 1998) largely underestimated the average age of introduced sequences in the E. coli genome, in particular, most of the 755 genes should be introduced into E. coli before, instead of after, the divergence of E. coli from the Salmonella lineage. Our study reveals that atypical G+C content and pattern of codon usage are not reliable indicators of horizontal gene transfer events.

Base Composition↗

PubMed2002

Cloning and characterization of the Zymobacter palmae pyruvate decarboxylase gene (pdc) and comparison to bacterial homologues.

Pyruvate decarboxylase (PDC) is the key enzyme in all homo-ethanol fermentations. Although widely distributed among plants, yeasts, and fungi, PDC is absent in animals and rare in bacteria (established for only three organisms). Genes encoding the three known bacterial pdc genes have been previously described and expressed as active recombinant proteins. The pdc gene from Zymomonas mobilis has been used to engineer ethanol-producing biocatalysts for use in industry. In this paper, we describe a new bacterial pdc gene from Zymobacter palmae. The pattern of codon usage for this gene appears quite similar to that for Escherichia coli genes. In E. coli recombinants, the Z. palmae PDC represented approximately 1/3 of the soluble protein. Biochemical and kinetic properties of the Z. palmae enzyme were compared to purified PDCs from three other bacteria. Of the four bacterial PDCs, the Z. palmae enzyme exhibited the highest specific activity (130 U mg of protein(-1)) and the lowest Km for pyruvate (0.24 mM). Differences in biochemical properties, thermal stability, and codon usage may offer unique advantages for the development of new biocatalysts for fuel ethanol production.

Amino Acid Sequence↗

PubMed2000

Rates of nucleotide substitution and mammalian nuclear gene evolution. Approximate and maximum-likelihood methods lead to different conclusions.

Rates and patterns of synonymous and nonsynonymous substitutions have important implications for the origin and maintenance of mammalian isochores and the effectiveness of selection at synonymous sites. Previous studies of mammalian nuclear genes largely employed approximate methods to estimate rates of nonsynonymous and synonymous substitutions. Because these methods did not account for major features of DNA sequence evolution such as transition/transversion rate bias and unequal codon usage, they might not have produced reliable results. To evaluate the impact of the estimation method, we analyzed a sample of 82 nuclear genes from the mammalian orders Artiodactyla, Primates, and Rodentia using both approximate and maximum-likelihood methods. Maximum-likelihood analysis indicated that synonymous substitution rates were positively correlated with GC content at the third codon positions, but independent of nonsynonymous substitution rates. Approximate methods, however, indicated that synonymous substitution rates were independent of GC content at the third codon positions, but were positively correlated with nonsynonymous rates. Failure to properly account for transition/transversion rate bias and unequal codon usage appears to have caused substantial biases in approximate estimates of substitution rates.

Animals↗

PubMed2002

Trends in codon and amino acid usage in Thermotoga maritima.

The usage of synonymous codons and the frequencies of amino acids were investigated in the complete genome of the bacterium Thermotoga maritima using a multivariate statistical approach. The GC3 content of each gene was the most prominent source of variation of codon usage. Surprisingly the usage of UGU and UGC (synonymous triplets coding for Cys, the least frequent amino acid in this species) was detected as the second most prominent source of variation. However, this result is probably an artifact due to the very low frequency of Cys together with the nonbiased composition of this genome. The third trend was related to the preferential usage of a subset of codons among highly expressed genes, and these triplets are presumed to be translationally optimal. Concerning the amino acid usage, the hydropathy level of each protein (and therefore the frequency of charged residues) was the main trend, while the second factor was related to the frequency of usage of the smaller residues, suggesting that the cell economy strongly influences the architecture of the proteins. The third axis of the analysis discriminated the usage of Phe, Tyr, Trp (aromatic residues) plus Cys, Met, and His. These six residues have in common the property of being the preferential targets of reactive oxygen species, and therefore the anaerobic condition of T. maritima is an important factor for the amino acid frequencies. Finally, the Cys content of each protein was the fourth trend.

Amino Acids↗

PubMed1991

msDNA of bacteria.

The msDNA-retron element represents the first prokaryotic member of the large and diverse retroelement family found in many eukaryotic genomes (Table II). This prokaryotic retroelement exists as a single copy element in the chromosome of two different bacterial groups: the common soil microbe M. xanthus and the enteric bacterium E. coli. It encodes an RT similar to the polymerases found in retroviruses, containing most of the strictly conserved amino acids found in all RTs. The RT is responsible for the production of an unusual extrachromosomal RNA-DNA molecule known as msDNA. Each composed of a short single strand of RNA and a short single strand of DNA, msDNAs vary considerably in their primary nucleotide sequences, but all share certain secondary structural features, including the unique 2',5' branch linkage that joins the 5' end of the DNA chain to the 2' position of an internal guanosine residue of the RNA strand. It is proposed that msDNA is synthesized by reverse transcription of a precursor RNA transcribed from a region of the retron containing the genes msr (encoding the RNA portion) and msd (encoding the DNA portion) and the ORF (encoding the RT). The precursor RNA transcript folds into a stable secondary structure that serves as both the primer and the template for the synthesis of msDNA. The msDNA-retron elements of E. coli are found in less than 10% of all strains observed, are heterogeneous in nature, and have an atypical aminoacid codon usage for this species, suggesting that this element was transmitted to E. coli by some other source. The presence of directly repeated 26-base-pair sequences flanking the junctions of the Ec67-retron of E. coli also suggests that it may be a mobile element. However, the msDNA-retrons of M. xanthus appear to be as old as other genes native to this species, based on codon-usage data for the RT genes and the fact that every strain of M. xanthus appears to have the same type of msDNA. If the msDNA-retron element originated with the myxobacteria, it would place the existence of retrons before the appearance of eukaryotic cells, suggesting that the bacterial element is perhaps the ancestral gene from which eukaryotic retroviruses and other retroelements evolved.(ABSTRACT TRUNCATED AT 400 WORDS)

Base Sequence↗

PubMed1999

Synonymous codon choices in the extremely GC-poor genome of Plasmodium falciparum: compositional constraints and translational selection.

We have analyzed the patterns of synonymous codon preferences of the nuclear genes of Plasmodium falciparum, a unicellular parasite characterized by an extremely GC-poor genome. When all genes are considered, codon usage is strongly biased toward A and T in third codon positions, as expected, but multivariate statistical analysis detects a major trend among genes. At one end genes display codon choices determined mainly by the extreme genome composition of this parasite, and very probably their expression level is low. At the other end a few genes exhibit an increased relative usage of a particular subset of codons, many of which are C-ending. Since the majority of these few genes is putatively highly expressed, we postulate that the increased C-ending codons are translationally optimal. In conclusion, while codon usage of the majority of P. falciparum genes is determined mainly by compositional constraints, a small number of genes exhibit translational selection.

Animals↗

PubMed2004

Gene "volatility" is most unlikely to reveal adaptation.

It has recently been claimed that adaptive molecular evolution can be detected within single genome sequences by use of gene "volatility" scores. However, the approach used was entirely based on the assumption that synonymous codon usage is normally shaped by selection for low volatility; this is most unlikely to be true. Furthermore, even if that assumption could be justified, the method would clearly lack power, detecting only genes where a very large number of nonsynonymous substitutions had occurred. Volatility scores are susceptible to other influences. The unusually high volatilities of the Mycobacterium tuberculosis and Plasmodium falciparum genes that were identified as putatively having undergone adaptive changes were largely the result of internally repetitive structures, in which unusual codon usage was caused by the mechanisms that generated this repetition rather than by adaptive changes.

Adaptation, Physiological↗

PubMed2005

A computational approach for identifying pathogenicity islands in prokaryotic genomes.

BACKGROUND: Pathogenicity islands (PAIs), distinct genomic segments of pathogens encoding virulence factors, represent a subgroup of genomic islands (GIs) that have been acquired by horizontal gene transfer event. Up to now, computational approaches for identifying PAIs have been focused on the detection of genomic regions which only differ from the rest of the genome in their base composition and codon usage. These approaches often lead to the identification of genomic islands, rather than PAIs. RESULTS: We present a computational method for detecting potential PAIs in complete prokaryotic genomes by combining sequence similarities and abnormalities in genomic composition. We first collected 207 GenBank accessions containing either part or all of the reported PAI loci. In sequenced genomes, strips of PAI-homologs were defined based on the proximity of the homologs of genes in the same PAI accession. An algorithm reminiscent of sequence-assembly procedure was then devised to merge overlapping or adjacent genomic strips into a large genomic region. Among the defined genomic regions, PAI-like regions were identified by the presence of homolog(s) of virulence genes. Also, GIs were postulated by calculating G+C content anomalies and codon usage bias. Of 148 prokaryotic genomes examined, 23 pathogenic and 6 non-pathogenic bacteria contained 77 candidate PAIs that partly or entirely overlap GIs. CONCLUSION: Supporting the validity of our method, included in the list of candidate PAIs were thirty four PAIs previously identified from genome sequencing papers. Furthermore, in some instances, our method was able to detect entire PAIs for those only partial sequences are available. Our method was proven to be an efficient method for demarcating the potential PAIs in our study. Also, the function(s) and origin(s) of a candidate PAI can be inferred by investigating the PAI queries comprising it. Identification and analysis of potential PAIs in prokaryotic genomes will broaden our knowledge on the structure and properties of PAIs and the evolution of bacterial pathogenesis.

Bacteria↗

PubMed1990

Genetic code 1990. Outlook.

The genetic code is evolving as shown by 9 departures from the universal code: 6 of them are in mitochondria and 3 are in nuclear codes. We propose that these changes are preceded by disappearance of a codon from coding sequences in mRNA of an organism or organelle. The function of the codon that disappears is taken by other, synonymous codons, so that there is no change in amino acid sequences of proteins. The deleted codon then reappears with a new function. Wobble pairing between anticodons and codons has evolved, starting with a single UNN anticodon pairing with 4 codons. Directional mutation pressure affects codon usage and may produce codon reassignments, especially of stop codons. Selenocysteine is coded by UGA, which is also a stop codon, and this anomaly is discussed. The outlook for discovery of more changes in the code is favorable, and open reading frames should be compared with actual sequential analyses of protein molecules in this search.

Anaerobiosis↗

PubMed2026

Dietary arginine drives codon-dependent MHC class I translation and improves immunity in colon tumorigenesis and respiratory viral infection.

Amino acid levels fluctuate across diverse pathological conditions. Whether such amino acid modulations directly shape pathophysiology by regulating host gene expression remains unknown. We found that extracellular arginine restriction, observed in cancer and infection, represses specific arginine tRNAs-directly suppressing translation of major histocompatibility complex I (MHC class I) and antigen presentation. Arginine regulation of MHC class I was codon-usage dependent, as synonymous codon mutations prevented MHC class I modulation. Dietary arginine restriction impaired anti-viral immunity against influenza and SARS-CoV-2 and increased colon tumorigenesis. Conversely, increasing arginine availability via dietary supplementation or myeloid-specific arginase 1 deletion enhanced MHC class I protein levels, suppressed colon tumorigenesis, and improved viral infection outcomes. These disease-modulating effects were abolished in β2-microglobulin (B2m)-deficient mice. Thus, dietary modulation of a single amino acid critically influences codon-biased translation and MHC class I-mediated immunity to respiratory viral infections and cancer, revealing an unexpected mechanism and disease hazard for arginine deficiency and highlighting potential for amino acid-based translation modulation therapy.

Animals↗

PubMed2006

Expression of feline immunodeficiency virus Vif is associated with reduced viral mutation rates without restoration of replication of vif mutant viruses.

The vif gene of lentiviruses has been demonstrated to be essential for efficient viral replication in many cell types. Although the Vif protein of feline immunodeficiency virus (FIV) displays limited homology to HIV-1 Vif, the role of vif in FIV replication is not known. We have examined the requirements of vif for replication of a FIV strain isolated from a non-domestic felid, Otocolobus manul (FIV-Oma). In agreement with others, we find that replication of FIV vif mutant molecular clones in CrFK cells is highly attenuated. Initial attempts to rescue vif mutant viruses in trans were limited by lack of detectable wild-type Vif expression from DNA constructs. We demonstrate that FIV-Oma Vif expression can be increased by re-synthesis of the gene to remove splice donor and acceptor sites as well as improving codon usage to a mammalian codon optimized model. Cellular localization of resynthesized Vif (Vif-RS) is cytoplasmic. Clonal stable transfectants expressing HA-tagged Vif-RS do not restore replication levels of vif mutant virus. However, in such cell lines, G-to-A mutation rates in replicating wild-type viruses are reduced.

Amino Acid Sequence↗

PubMed2006

Designing and transgenic expression of melanin gene in tobacco trichome and cotton fiber.

In Streptomyces antibioticus, there are two genes TYRA and ORF438 required for the melanin biogenesis. To investigate whether expression of these two genes in cotton can change cotton fiber colour, we modified the TYRA and ORF438 genes to make their codon usage closer to the codon preference of cotton fiber genes. The resulting versions of these two genes were referred to as DTYRA and DORF438, respectively. Vacuolar targeting signals were also added to their ends. Under the cotton fiber specific LTP3 promoter, DORF438 and DTYRA were first transformed into model plant tobacco (Nicotiana tabacum). Molecular analyses showed that both the DORF438 and DTYRA genes were successfully expressed in transgenic plants, and the melanin deposition was observed in the trichomes of transgenic tobacco. Excitedly, when the same DORF438 and DTYRA expression cassettes were transformed into cotton (Gossypium hirsutum L.) by pollen tube pathway, the colour of cotton fiber changed from white to brown. Molecular analyses confirmed that both genes were transformed into cotton and expressed successfully. All these results indicate that the synthesized DOFR438 and DTYRA genes can work well in tobacco and cotton. Our study may provide a potential method for modifying the colour of cotton fiber.

Amino Acid Sequence↗

PubMed1996

Site-specific codon bias in bacteria.

Sequences of the gapA and ompA genes from 10 genera of enterobacteria have been analyzed. There is strong bias in codon usage, but different synonymous codons are preferred at different sites in the same gene. Site-specific preference for unfavored codons is not confined to the first 100 codons and is usually manifest between two codons utilizing the same tRNA. Statistical analyses, based on conclusions reached in an accompanying paper, show that the use of an unfavored codon at a given site in different genera is not due to common descent and must therefore be caused either by sequence-specific mutation or sequence-specific selection. Reasons are given for thinking that sequence-specific mutation cannot be responsible. We are unable to explain the preference between synonymous codons ending in C or T, but synonymous choice between A and G at third sites is largely explained by avoidance of AG-G (where the hyphen indicates the boundary between codons). We also observed that the preferred codon for proline in Enterobacter cloacea has changed from CCG to CCA.

Bacterial Outer Membrane Proteins↗