Environmental shaping of codon usage and functional adaptation across microbial communities

Microbial communities represent the largest portion of the Earth’s biomass. Metagenomics projects use high-throughput sequencing to survey these communities and shed light on genetic capabilities that enable microbes to inhabit every corner of the biosphere. Metagenome studies are generally based on (i) classifying and ranking functions of identified genes; and (ii) estimating the phyletic distribution of constituent microbial species. To understand microbial communities at the systems level, it is necessary to extend these studies beyond the species’ boundaries and capture higher levels of metabolic complexity. We evaluated 11 metagenome samples and demonstrated that microbes inhabiting the same ecological niche share common preferences for synonymous codons, regardless of their phylogeny. By exploring concepts of translational optimization through codon usage adaptation, we demonstrated that community-wide bias in codon usage can be used as a prediction tool for lifestyle-specific genes across the entire microbial community, effectively considering microbial communities as meta-genomes. These findings set up a ‘functional metagenomics’ platform for the identification of genes relevant for adaptations of entire microbial communities to environments. Our results provide valuable arguments in defining the concept of microbial species through the context of their interactions within the community.     

No evidence for tissue-specific adaptation of synonymous codon usage in humans

It has been proposed that the synonymous codon usage of human tissue-specific genes was under selective pressure to modulate the expression of proteins by codon-mediated translational control (Plotkin, J. B., H. Robins, and A. J. Levine. 2004. Tissue-specific codon usage and the expression of human genes. Proc. Natl. Acad. Sci. USA 101:12588-12591.) To test this model, we analyzed by internal correspondence analysis the codon usage of 2,126 human tissue-specific genes expressed in 18 different tissues. We confirm that synonymous codon usage differs significantly between the tissues. However, the effect is very weak: the variability of synonymous codon usage between tissues represents only 2.3% of the total codon usage variability. Moreover, this variability is directly linked to isochore-scale (>100 kb) variability of GC-content that affect both coding and introns or intergenic regions. This demonstrates that variations of synonymous codon usage between tissue-specific genes expressed in different tissues are due to regional variations of substitution patterns and not to translational selection.     

Viral adaptation to host: a proteome‐based analysis of codon usage and amino acid preferences

Viruses differ markedly in their specificity toward host organisms. Here, we test the level of general sequence adaptation that viruses display toward their hosts. We compiled a representative data set of viruses that infect hosts ranging from bacteria to humans. We consider their respective amino acid and codon usages and compare them among the viruses and their hosts. We show that bacteria‐infecting viruses are strongly adapted to their specific hosts, but that they differ from other unrelated bacterial hosts. Viruses that infect humans, but not those that infect other mammals or aves, show a strong resemblance to most mammalian and avian hosts, in terms of both amino acid and codon preferences. In groups of viruses that infect humans or other mammals, the highest observed level of adaptation of viral proteins to host codon usages is for those proteins that appear abundantly in the virion. In contrast, proteins that are known to participate in host‐specific recognition do not necessarily adapt to their respective hosts. The implication for the potential of viral infectivity is discussed.     

Coevolution of codon usage and tRNA genes leads to alternative stable states of biased codon usage

The typical number of tRNA genes in bacterial genomes is around 50, but this number varies from under 30 to over 120. We argue that tRNA gene copy numbers evolve in response to translational selection. In rapidly multiplying organisms, the time spent in translation is a limiting factor in cell division; hence, it pays to duplicate tRNA genes, thereby increasing the concentration of tRNA molecules in the cell and speeding up translation. In slowly multiplying organisms, translation time is not a limiting factor, so the overall translational cost is minimized by reducing the tRNAs to only one copy of each required gene. Translational selection also causes a preference for codons that are most rapidly translated by the current tRNAs; hence, codon usage and tRNA gene content will coevolve to a state where each is adapted to the other. We show that there is often more than one stable coevolved state. This explains why different combinations of tRNAs and codon bias can exist for different amino acids in the same organism. We analyze a set of 80 complete bacterial genomes and show that the theory predicts many of the trends that are seen in these data.     

Comparative genome analysis of six malarial parasites using codon usage bias based tools

Codon usage bias (CUB) is an omnipresent phenomenon, which occurs in nearly all organisms. Previous studies of codon bias in Plasmodium species were based on a limited dataset. This study uses whole genome datasets for comparative genome analysis of six Plasmodium species using CUB and other related methods for the first time. Codon usage bias, compositional variation in translated amino acid frequency, effective number of codons and optimal codons are analyzed for P.falciparum, P.vivax, P.knowlesi, P.berghei, P.chabaudii and P.yoelli. A plot of effective number of codons versus GC3 shows their differential codon usage pattern arises due to a combination of mutational and translational selection pressure. The increased relative usage of adenine and thymine ending optimal codons in highly expressed genes of P.falciparum is the result of higher composition biased pressure, and usage of guanine and cytosine bases at third codon position can be explained by translational selection pressure acting on them. While higher usage of adenine and thymine bases at third codon position in optimal codons of P.vivax highlights the role of translational selection pressure apart from composition biased mutation pressure in shaping their codon usage pattern. The frequency of those amino acids that are encoded by AT ending codons are significantly high in P.falciparum due to action of high composition biased mutational pressure compared with other Plasmodium species. The CUB variation in the three rodent parasites, P.berghei, P.chabaudii and P.yoelli is strikingly similar to that of P.falciparum. The simian and human malarial parasite, P.knowlesi shows a variation in codon usage bias similar to P.vivax but on closer study there are differences confirmed by the method of Principal Component Analysis (PCA).

Abbreviations

CDS - Coding sequences, GC1 - GC composition at first site of codon, GC2 - GC composition at second site of codon, GC3 - GC composition at third site of codon, Ala - Alanine, Arg - Arginine, Asn - Asparagine, Asp - Aspartic acid, Cys - Cysteine, Gln - Glutamine Glu - Glutamic acid Gly - Glycine His - Histidine Ile - Isoleucine Leu - Leucine Lys - Lysine Met - Methionine Phe - Phenylalanine Pro - Proline Ser - Serine Thr - Threonine Trp - Tryptophan Tyr - Tyrosine Val - Valine.     

Selection at the amino acid level can influence synonymous codon usage: implications for the study of codon adaptation in plastid genes

A previously employed method that uses the composition of noncoding DNA as the basis of a test for selection between synonymous codons in plastid genes is reevaluated. The test requires the assumption that in the absence of selective differences between synonymous codons the composition of silent sites in coding sequences will match the composition of noncoding sites. It is demonstrated here that this assumption is not necessarily true and, more generally, that using compositional properties to draw inferences about selection on silent changes in coding sequences is much more problematic than commonly assumed. This is so because selection on nonsynonymous changes can influence the composition of synonymous sites (i.e., codon usage) in a complex manner, meaning that the composition biases of different silent sites, including neutral noncoding DNA, are not comparable. These findings also draw into question the commonly utilized method of investigating how selection to increase translation accuracy influences codon usage. The work then focuses on implications for studies that assess codon adaptation, which is selection on codon usage to enhance translation rate, in plastid genes. A new test that does not require the use of noncoding DNA is proposed and applied. The results of this test suggest that far fewer plastid genes display codon adaptation than previously thought.     

Universal function-specificity of codon usage

Synonymous codon usage has long been known as a factor that affects average expression level of proteins in fast-growing microorganisms, but neither its role in dynamic changes of expression in response to environmental changes nor selective factors shaping it in the genomes of higher eukaryotes have been fully understood. Here, we propose that codon usage is ubiquitously selected to synchronize the translation efficiency with the dynamic alteration of protein expression in response to environmental and physiological changes. Our analysis reveals that codon usage is universally correlated with gene function, suggesting its potential contribution to synchronized regulation of genes with similar functions. We directly show that coexpressed genes have similar synonymous codon usages within the genomes of human, yeast, Caenorhabditis elegans and Escherichia coli. We also demonstrate that perturbing the codon usage directly affects the level or even direction of changes in protein expression in response to environmental stimuli. Perturbing tRNA composition also has tangible phenotypic effects on the cell. By showing that codon usage is universally function-specific, our results expand, to almost all organisms, the notion that cells may need to dynamically alter their intracellular tRNA composition in order to adapt to their new environment or physiological role.     

A backtranslation method based on codon usage strategy

This study describes a method for the backtranslation of an aminoacidic sequence, an extremely useful tool for various experimental approaches. It involves two computer programs CLUSTER and BACKTR written in Fortran 77 running on a VAX/VMS computer. CLUSTER generates a reliable codon usage table through a cluster analysis, based on a chi 2-like distance between the sequences. BACKTR produces backtranslated sequences according to different options when use is made of the codon usage table obtained in addition to selecting the least ambiguous potential oligonucleotide probes within an aminoacidic sequence. The method was tested by applying it to 158 yeast genes.     

Clonorchis sinensis: codon usage in nuclear genes

Codon usage in Clonorchis sinensis was analyzed using 12,515 codons from 38 coding sequences. Total GC content was 49.83%, and GC1, GC2 and GC3 contents were 56.32%, 43.15% and 50.00%, respectively. The effective number of codons converged at 51-53 codons. When plotted against total GC content or GC3, codon usage was distributed in relation to GC3 biases. Relative synonymous codon usage for each codon revealed a single major trend, which was highly correlated with GC content at the third position when codons began with A or U at the first two positions. In codons beginning with G or C base at the first two positions, the G or C base rarely occurred at the third position. These results suggest that codon usage is shaped by a bias towards G or C at the third base, and that this is affected by the first and second bases.     

The effect of context on synonymous codon usage in genes with low codon usage bias.

The effect of neighbouring bases on the usage of synonymous codons in genes with low codon usage bias in yeast and E. coli is examined. The codon adaptation index is employed to identify a group of genes in each organism with low codon usage bias, which are likely to be weakly expressed. A similar pattern is found in complementary sequences with respect to synonymous usage of A vs G or of U vs C. It is suggested that this may reflect an effect of context on mutation rates in weakly expressed genes.     

Mutation-selection models of codon substitution and their use to estimate selective strengths on codon usage

Current models of codon substitution are formulated at the levels of nucleotide substitution and do not explicitly consider the separate effects of mutation and selection. They are thus incapable of inferring whether mutation or selection is responsible for evolution at silent sites. Here we implement a few population genetics models of codon substitution that explicitly consider mutation bias and natural selection at the DNA level. Selection on codon usage is modeled by introducing codon-fitness parameters, which together with mutation-bias parameters, predict optimal codon frequencies for the gene. The selective pressure may be for translational efficiency and accuracy or for fine-tuning translational kinetics to produce correct protein folding. We apply the models to compare mitochondrial and nuclear genes from several mammalian species. Model assumptions concerning codon usage are found to affect the estimation of sequence distances (such as the synonymous rate d(S), the nonsynonymous rate d(N), and the rate at the 4-fold degenerate sites d(4)), as found in previous studies, but the new models produced very similar estimates to some old ones. We also develop a likelihood ratio test to examine the null hypothesis that codon usage is due to mutation bias alone, not influenced by natural selection. Application of the test to the mammalian data led to rejection of the null hypothesis in most genes, suggesting that natural selection may be a driving force in the evolution of synonymous codon usage in mammals. Estimates of selection coefficients nevertheless suggest that selection on codon usage is weak and most mutations are nearly neutral. The sensitivity of the analysis on the assumed mutation model is discussed.     

A large-scale analysis of codon usage bias in 4868 bacterial genomes shows association of codon adaptation index with GC content,protein functional domains and bacterial phenotypes

Multiple synonymous codons code for the same amino acid, resulting in the degeneracy of the genetic code and in the preferred used of some codons called codon bias usage (CBU). We performed a large-scale analysis of codon usage bias analysing the distribution of the codon adaptation index (CAI) and the codon relative adaptiveness index (RA) in 4868 bacterial genomes. We found that CAI values differ significantly between protein functional domains and part of the protein outside domains and show how CAI, GC content and preferred usage of polymerase III alpha subunits are related. Additionally, we give evidence of the association between CAI and bacterial phenotypes.     

A standardized set of metrics to assess and monitor tree invasions

Scientists, managers, and policy-makers need functional and effective metrics to improve our understanding and management of biological invasions. Such metrics would help to assess progress towards management goals, increase compatibility across administrative borders, and facilitate comparisons between invasions. Here we outline key characteristics of tree invasions (status, abundance, spatial extent, and impact), discuss how each of these characteristics changes with time, and examine potential metrics to describe and monitor them. We recommend quantifying tree invasions using six metrics: (a) current status in the region; (b) potential status; (c) the number of foci requiring management; (d) area of occupancy (AOO) (i.e. compressed canopy area or net infestation); (e) extent of occurrence (EOO) (i.e. range size or gross infestation); and (f) observations of current and potential impact. We discuss how each metric can be parameterised (e.g. we include a practical method for classifying the current stage of invasion for trees following Blackburn’s unified framework for biological invasions); their potential management value (e.g. EOO provides an indication of the area over which management is needed); and how they can be used in concert (e.g. combining AOO and EOO can provide insights into invasion dynamics; and we use potential status and threat together to develop a simple risk analysis tool). Based on these metrics, we propose a standardized template for reporting tree invasions that we hope will facilitate cross-species and inter-regional comparisons. While we feel this represents a valuable step towards standardized reporting, there is an urgent need to develop more consistent metrics for impact and threat, and for many specific purposes additional metrics are still needed (e.g. detectability is required to assess the feasibility of eradication).     

Codon usage divergence of homologous vertebrate genes and codon usage clock

Summary This paper is concerned with the divergence of synonymous codon usage and its bias in three homologous genes within vertebrate species. Genetic distances among species are described in terms of synonymous codon usage divergence and the correlation is found between the genetic distances and taxonomic distances among species under study. A codon usage clock is reported in alphaglobin and beta-globin. A method is developed to define the synonymous codon preference bias and it is observed that the bias changes considerably among species.     

P-value based visualization of codon usage data

Two important and not yet solved problems in bacterial genome research are the identification of horizontally transferred genes and the prediction of gene expression levels. Both problems can be addressed by multivariate analysis of codon usage data. In particular dimensionality reduction methods for visualization of multivariate data have shown to be effective tools for codon usage analysis. We here propose a multidimensional scaling approach using a novel similarity measure for codon usage tables. Our probabilistic similarity measure is based on P-values derived from the well-known chi-square test for comparison of two distributions. Experimental results on four microbial genomes indicate that the new method is well-suited for the analysis of horizontal gene transfer and translational selection. As compared with the widely-used correspondence analysis, our method did not suffer from outlier sensitivity and showed a better clustering of putative alien genes in most cases.     

Evolution of synonymous codon usage in metazoans

The vast amount of data generated by genome projects and the recent development of population genetics models make comparative sequence analyses a very powerful approach with which to detect the footprints of selection. Studies on synonymous codon usage show that traits with minuscule phenotypic effects can be molded by natural selection. But variations in mutation patterns and processes of biased gene conversion make it difficult to distinguish between selective and neutral evolutionary processes.     

圆红冬孢酵母的密码子用法分析

运用CodonW等软件,分析了圆红冬孢酵母Rhodosporidium toruloides基因组中191个蛋白质编码基因的密码子使用模式,包括密码子3个位置上的GC含量、有效密码子数和密码子使用频率。圆红冬孢酵母有效密码子数ENc值为38.9,密码子GC含量为63%,密码子第三位GC含量为78.3%,且偏好使用G或C结尾的密码子,确定了圆红冬孢酵母R. toruloides的21个高表达优越密码子。研究发现,圆红冬孢酵母与毕赤酵母、酿酒酵母、大肠杆菌和拟南芥在密码子使用频率上有较大差异,而与解脂耶氏酵母和果蝇差异相对较小。研究结果对提高外源基因在圆红冬孢酵母中表达效率及相关代谢工程和合成生物学研究有一定意义。     

A cross talk between codon usage bias in human oncogenes

Background: Oncogenes are the genes that have the potential to induce cancer. The extent and origin of codon usage bias is an important indicator of the forces shaping genome evolution in living organisms. Results: We observed moderate correlations between gene expression as measured by CAI and GC content at any codon site. The findings of our results showed that there is a significant positive correlation (Spearman''s r= 0.45, P<0.01) between GC content at first and second codon position with that of third codon position. Further, striking negative correlation (r = -0.771, P < 0.01) between ENC with the GC3s values of each gene and positive correlation (r=0.644, P<0.01) in between CAI and ENC was also observed. Conclusions: The mutation pressure is the major determining factor in shaping the codon usage pattern of oncogenes rather than natural selection since its effects are present at all codon positions. The results revealed that codon usage bias determines the level of oncogene expression in human. Highly expressed oncogenes had rich GC contents with high degree of codon usage bias.     

病毒密码子使用频率研究进展

密码子使用频率的研究多集中在自养生物中,对于寄生生物如病毒的研究相对较少,近些年的研究表明某些病毒基因的密码子使用频率和宿主细胞不完全匹配,密码子使用在病毒和宿主的相互作用中起了重要的作用。本对病毒密码子使用频率的特点,影响病毒密码子使用频率的因素,几种典型病毒的密码子使用特点和密码子使用频率研究的方法做了论述。