Comparison of codon usage measures and their applicability in prediction of microbial gene expressivity

Background  

There are a number of methods (also called: measures) currently in use that quantify codon usage in genes. These measures are often influenced by other sequence properties, such as length. This can introduce strong methodological bias into measurements; therefore we attempted to develop a method free from such dependencies. One of the common applications of codon usage analyses is to quantitatively predict gene expressivity.     

E-CAI: a novel server to estimate an expected value of Codon Adaptation Index (eCAI)

Background  

The Codon Adaptation Index (CAI) is a measure of the synonymous codon usage bias for a DNA or RNA sequence. It quantifies the similarity between the synonymous codon usage of a gene and the synonymous codon frequency of a reference set. Extreme values in the nucleotide or in the amino acid composition have a large impact on differential preference for synonymous codons. It is thence essential to define the limits for the expected value of CAI on the basis of sequence composition in order to properly interpret the CAI and provide statistical support to CAI analyses. Though several freely available programs calculate the CAI for a given DNA sequence, none of them corrects for compositional biases or provides confidence intervals for CAI values.     

Efficient computation of absent words in genomic sequences

Background  

Analysis of sequence composition is a routine task in genome research. Organisms are characterized by their base composition, dinucleotide relative abundance, codon usage, and so on. Unique subsequences are markers of special interest in genome comparison, expression profiling, and genetic engineering. Relative to a random sequence of the same length, unique subsequences are overrepresented in real genomes. Shortest words absent from a genome have been addressed in two recent studies.     

Gene identification and protein classification in microbial metagenomic sequence data via incremental clustering

Background  

The identification and study of proteins from metagenomic datasets can shed light on the roles and interactions of the source organisms in their communities. However, metagenomic datasets are characterized by the presence of organisms with varying GC composition, codon usage biases etc., and consequently gene identification is challenging. The vast amount of sequence data also requires faster protein family classification tools.     

Sequence similarity is more relevant than species specificity in probabilistic backtranslation

Background  

Backtranslation is the process of decoding a sequence of amino acids into the corresponding codons. All synthetic gene design systems include a backtranslation module. The degeneracy of the genetic code makes backtranslation potentially ambiguous since most amino acids are encoded by multiple codons. The common approach to overcome this difficulty is based on imitation of codon usage within the target species.     

The SeqWord Genome Browser: an online tool for the identification and visualization of atypical regions of bacterial genomes through oligonucleotide usage

Background  

Data mining in large DNA sequences is a major challenge in microbial genomics and bioinformatics. Oligonucleotide usage (OU) patterns provide a wealth of information for large scale sequence analysis and visualization. The purpose of this research was to make OU statistical analysis available as a novel web-based tool for functional genomics and annotation. The tool is also available as a downloadable package.     

Differentiation of regions with atypical oligonucleotide composition in bacterial genomes

Background  

Complete sequencing of bacterial genomes has become a common technique of present day microbiology. Thereafter, data mining in the complete sequence is an essential step. New in silico methods are needed that rapidly identify the major features of genome organization and facilitate the prediction of the functional class of ORFs. We tested the usefulness of local oligonucleotide usage (OU) patterns to recognize and differentiate types of atypical oligonucleotide composition in DNA sequences of bacterial genomes.     

Relationship of SARS-CoV to other pathogenic RNA viruses explored by tetranucleotide usage profiling

Background  

The exact origin of the cause of the Severe Acute Respiratory Syndrome (SARS) is still an open question. The genomic sequence relationship of SARS-CoV with 30 different single-stranded RNA (ssRNA) viruses of various families was studied using two non-standard approaches. Both approaches began with the vectorial profiling of the tetra-nucleotide usage pattern V for each virus. In approach one, a distance measure of a vector V, based on correlation coefficient was devised to construct a relationship tree by the neighbor-joining algorithm. In approach two, a multivariate factor analysis was performed to derive the embedded tetra-nucleotide usage patterns. These patterns were subsequently used to classify the selected viruses.     

TISs-ST: a web server to evaluate polymorphic translation initiation sites and their reflections on the secretory targets

Background  

The nucleotide sequence flanking the translation initiation codon (start codon context) affects the translational efficiency of eukaryotic mRNAs, and may indicate the presence of an alternative translation initiation site (TIS) to produce proteins with different properties. Multi-targeting may reflect the translational variability of these other protein forms. In this paper we present a web server that performs computations to investigate the usage of alternative translation initiation sites for the synthesis of new protein variants that might have different functions.     

Molecular evolution of synonymous codon usage in <Emphasis Type="Italic">Populus</Emphasis>

Background  

Evolution of synonymous codon usage is thought to be determined by a balance between mutation, genetic drift and natural selection on translational efficiency. However, natural selection on codon usage is considered to be a weak evolutionary force and selection on codon usage is expected to be strongest in species with large effective population sizes.     

Quantitative relationship between synonymous codon usage bias and GC composition across unicellular genomes

Background  

Codon usage bias has been widely reported to correlate with GC composition. However, the quantitative relationship between codon usage bias and GC composition across species has not been reported.     

Accelerated probabilistic inference of RNA structure evolution

Background  

Pairwise stochastic context-free grammars (Pair SCFGs) are powerful tools for evolutionary analysis of RNA, including simultaneous RNA sequence alignment and secondary structure prediction, but the associated algorithms are intensive in both CPU and memory usage. The same problem is faced by other RNA alignment-and-folding algorithms based on Sankoff's 1985 algorithm. It is therefore desirable to constrain such algorithms, by pre-processing the sequences and using this first pass to limit the range of structures and/or alignments that can be considered.     

Evolutionary history of selenocysteine incorporation from the perspective of SECIS binding proteins

Background  

The co-translational incorporation of selenocysteine into nascent polypeptides by recoding the UGA stop codon occurs in all domains of life. In eukaryotes, this event requires at least three specific factors: SECIS binding protein 2 (SBP2), a specific translation elongation factor (eEFSec), selenocysteinyl tRNA, and a cis -acting selenocysteine insertion sequence (SECIS) element in selenoprotein mRNAs. While the phylogenetic relationships of selenoprotein families and the evolution of selenocysteine usage are well documented, the evolutionary history of SECIS binding proteins has not been explored.     

Measure of synonymous codon usage diversity among genes in bacteria

Background  

In many bacteria, intragenomic diversity in synonymous codon usage among genes has been reported. However, no quantitative attempt has been made to compare the diversity levels among different genomes. Here, we introduce a mean dissimilarity-based index (Dmean) for quantifying the level of diversity in synonymous codon usage among all genes within a genome.     

Variation in global codon usage bias among prokaryotic organisms is associated with their lifestyles

Background  

It is widely acknowledged that synonymous codons are used unevenly among genes in a genome. In organisms under translational selection, genes encoding highly expressed proteins are enriched with specific codons. This phenomenon, termed codon usage bias, is common to many organisms and has been recognized as influencing cellular fitness. This suggests that the global extent of codon usage bias of an organism might be associated with its phenotypic traits.     

Adaptable data management for systems biology investigations

Background  

Within research each experiment is different, the focus changes and the data is generated from a continually evolving barrage of technologies. There is a continual introduction of new techniques whose usage ranges from in-house protocols through to high-throughput instrumentation. To support these requirements data management systems are needed that can be rapidly built and readily adapted for new usage.     

Codon usage is associated with the evolutionary age of genes in metazoan genomes

Background  

Codon usage may vary significantly between different organisms and between genes within the same organism. Several evolutionary processes have been postulated to be the predominant determinants of codon usage: selection, mutation, and genetic drift. However, the relative contribution of each of these factors in different species remains debatable. The availability of complete genomes for tens of multicellular organisms provides an opportunity to inspect the relationship between codon usage and the evolutionary age of genes.     

Clinical outcomes and immune benefits of anti-epileptic drug therapy in HIV/AIDS

Background  

Anti-epileptic drugs (AEDs) are frequently prescribed to persons with HIV/AIDS receiving combination antiretroviral therapy (cART) although the extent of AED use and their interactions with cART are uncertain. Herein, AED usage, associated toxicities and immune consequences were investigated.     

CpG site degeneration triggered by the loss of functional constraint created a highly polymorphic macaque drug-metabolizing gene, CYP1A2

Background

Duplicated genes frequently experience asymmetric rates of sequence evolution. Relaxed selective constraints and positive selection have both been invoked to explain the observation that one paralog within a gene-duplicate pair exhibits an accelerated rate of sequence evolution. In the majority of studies where asymmetric divergence has been established, there is no indication as to which gene copy, ancestral or derived, is evolving more rapidly. In this study we investigated the effect of local synteny (gene-neighborhood conservation) and codon usage on the sequence evolution of gene duplicates in the S. cerevisiae genome. We further distinguish the gene duplicates into those that originated from a whole-genome duplication (WGD) event (ohnologs) versus small-scale duplications (SSD) to determine if there exist any differences in their patterns of sequence evolution.

Results

For SSD pairs, the derived copy evolves faster than the ancestral copy. However, there is no relationship between rate asymmetry and synteny conservation (ancestral-like versus derived-like) in ohnologs. mRNA abundance and optimal codon usage as measured by the CAI is lower in the derived SSD copies relative to ancestral paralogs. Moreover, in the case of ohnologs, the faster-evolving copy has lower CAI and lowered expression.

Conclusions

Together, these results suggest that relaxation of selection for codon usage and gene expression contribute to rate asymmetry in the evolution of duplicated genes and that in SSD pairs, the relaxation of selection stems from the loss of ancestral regulatory information in the derived copy.