Codon usage and genome evolution

The rates and patterns of evolution at silent sites in codons reveal much about the basic features of molecular evolution. Recent increases in the amount of sequence data available for various species and more precise knowledge of the chromosomal locations of those sequences, coming in particular from genome projects, reveal that some features of molecular evolution vary around the genome.     

Codon usage bias and evolutionary analyses of Zika virus genomes

Zika virus (ZIKV) is a member of the family Flaviviridae and contains a single-stranded RNA genome with positive-polarity. Like Dengue, Zika virus uses Aedes aegypti mosquito as a vector to infect human with a wide range of clinical signs, from asymptomatic to influenza-like syndrome. Despite significant progress in genomic analyses, how a viral relationship with two different hosts affect the overall fitness, constancy, and dodging of hosts immune system are elusive. Here we analyzed Zika virus codon-based evolution using eleven strains from different geographical locations. The overall codon usage was similar and slightly bias among all strains. An occurrence of A-ending in highly-preferred codons and analysis by various approaches strongly suggests that mutational bias is the main force shaping codon usage in this virus. However, natural selection and geographical realities cannot be ignored in marginal influence on codon usage. The viral genomes naturally favor Aedes aegypti over human host for tRNA pool in translation. Such findings will assist researchers in understanding elements contribute to viral adaptation and evolutionary setup with hosts.     

Codon usage and bias in mitochondrial genomes of parasitic platyhelminthes

Sequences of the complete protein-coding portions of the mitochondrial (mt) genome were analysed for 6 species of cestodes (including hydatid tapeworms and the pork tapeworm) and 5 species of trematodes (blood flukes and liver- and lung-flukes). A near-complete sequence was also available for an additional trematode (the blood fluke Schistosoma malayensis). All of these parasites belong to a large flatworm taxon named the Neodermata. Considerable variation was found in the base composition of the protein-coding genes among these neodermatans. This variation was reflected in statistically-significant differences in numbers of each inferred amino acid between many pairs of species. Both convergence and divergence in nucleotide, and hence amino acid, composition was noted among groups within the Neodermata. Considerable variation in skew (unequal representation of complementary bases on the same strand) was found among the species studied. A pattern is thus emerging of diversity in the mt genome in neodermatans that may cast light on evolution of mt genomes generally.     

痘苗病毒基因组密码子使用频率分析

密码子使用的差别是普遍存在的现象,每一个密码子被某些生物偏爱,而在另一些生物中则很少使用.以往这方面的研究多集中在自养生物中,而对纯寄生的病毒本身及其与宿主细胞基因密码子使用频率关系的研究则很少.分析痘苗病毒哥本哈根株189个基因的密码子使用频率发现:总体上痘苗病毒偏爱使用以A/U为结尾的密码子;基因的异质性不强,没有影响密码子使用的主要趋势;在不同转录方向上和表达时相上,基因密码子使用略有不同;不同功能的基因其密码子使用上差别较大;晚期基因比早期基因与宿主密码子使用频率的差别大.上述结果表明:密码子是影响病毒和细胞相互作用、保证其自身生存的重要机制.     

Codon usage bias in human cytomegalovirus and its biological implication

Human cytomegalovirus (HCMV) infection, a worldwide contagion, causes a serious disorder in infected individuals. Analysis of codon usage can reveal much molecular information about this virus. The effective number of codon (ENC) values, relative synonymous codon usage (RSCU) values, codon adaptation index (CAI), and nucleotide contents was investigated in approximately 160 coding sequences (CDS) among 17 human cytomegalovirus genomes using the software CodonW. Linear regression analysis and logistic regression were performed to explore the preliminary data. The results showed that, overall, HCMV genomes had low codon usage bias (mean ENC = 47.619). However, the ENC of individual CDS varied widely and was distributed unevenly between host-related genes and viral-self-function genes (P = 0.002, odds ratio (OR) = 3.194), as did the GC content (P = 0.016, OR = 2.178). The ENC values correlated with CAI, GC content, and the nucleotide composing at the 3rd codon position (GC3s) (P < 0.001). There was a significant variation in the codon preference that depended on the RSCU data. The predicted ENC curve suggested that mutational pressure, rather than natural selection, was one of the main factors that determined the codon usage bias in HCMV. Among 123 genes with known function, the genes related to viral self-replication and viral–host interaction showed different ENC and CAI values, and GC and GC3s contents. In conclusion, the detailed codon usage bias theoretically revealed information concerning HCMV evolution and could be a valuable additional parameter for HCMV gene function research.     

The evolution of human influenza viruses.

The evolution of influenza viruses results in (i) recurrent annual epidemics of disease that are caused by progressive antigenic drift of influenza A and B viruses due to the mutability of the RNA genome and (ii) infrequent but severe pandemics caused by the emergence of novel influenza A subtypes to which the population has little immunity. The latter characteristic is a consequence of the wide antigenic diversity and peculiar host range of influenza A viruses and the ability of their segmented RNA genomes to undergo frequent genetic reassortment (recombination) during mixed infections. Contrasting features of the evolution of recently circulating influenza AH1N1, AH3N2 and B viruses include the rapid drift of AH3N2 viruses as a single lineage, the slow replacement of successive antigenic variants of AH1N1 viruses and the co-circulation over some 25 years of antigenically and genetically distinct lineages of influenza B viruses. Constant monitoring of changes in the circulating viruses is important for maintaining the efficacy of influenza vaccines in combating disease.     

Codon usage bias as a function of generation time and life expectancy

It has recently been demonstrated that human natural codon usage bias is optimized towards a higher buffering capacity to mutations (measured as the tendency of single point mutations in a DNA sequence to yield the same or similar amino acids) compared to random sequences. In this work, we investigate this phenomenon further by analyzing the natural DNA of four different species (human, mouse, zebrafish and fruit fly) to determine whether such a tolerance to mutations is correlated with the life span and age of sexual maturation for the corresponding organisms. We also propose a new measure to quantify the buffering capacity of a DNA sequence to mutations that takes into account the observed mutation rates within every genome and the effect of the corresponding mutation.Our results suggest there is a propensity for tolerance to mutations that is positively correlated with the life expectancy of the considered organisms. Moreover, random sequences that are constrained to produce the same protein as the naturally occurring sequences are found to be more buffered than completely random sequences while being less buffered than the natural sequences. These results suggest that optimization toward protective mechanisms tolerant to mutations is correlated with both life expectancy and age to sexual maturity at both the levels of codon usage bias and the bias of the natural sequence of codons itself.     

伪狂犬病病毒基因编码区碱基组成与密码子使用偏差

由于伪狂犬病病毒(PRV)中G C含量高达74％,至今尚没有一个毒株完成全基因组测序。对已知的68个PRV基因编码区序列碱基组成及密码子使用现象进行了统计分析,结果发现PRV基因中存在非常强的密码子使用偏差。所有68个PRV基因编码区密码子第三位总的G C含量为96．24％,其中UL48基因高达99．52％。PRV基因偏向于使用富含GC的密码子,特别是以C或G结尾的密码子。此外,还发现PRV中G C含量变化较大的UL48、UL40、UL14和IE180等基因附近正好与已知的PRV基因组复制起始区相对应。根据基因功能将PRV基因分为6类进行分析发现,基因功能相同或相近的基因其密码子使用模式相似,其中调节基因的同义密码子相对使用度(RSCU)与其他基因有显著差异,在调节基因中以C结尾的密码子的RSCU值远大于其他同义密码子。最后,对PRV基因氨基酸组成差异进行多元分析,发现不同功能的PRV基因在对应分析图上分布不同,表明PRV基因密码子使用模式可能与基因功能相关。     

Codon usage and gene expression.

The hypothesis that codon usage regulates gene expression at the level of translation is tested. Codon usage of Escherichia coli and phage lambda is compared by correspondence analysis, and the basis of this hypothesis is examined by connecting codon and tRNA distributions to polypeptide elongation kinetics. Both approaches indicate that if codon usage was random tRNA limitation would only affect the rarest tRNA species. General discrimination against their cognate codons indicates that polypeptide elongation rates are maintained constant. Thus, differences in expression of E. coli genes are not a consequence of their variable codon usage. The preference of codons recognized by the most abundant tRNAs in E. coli genes encoding abundant proteins is explained by a constraint on the cost of proof-reading.     

Codon Usage Biases of Transposable Elements and Host Nuclear Genes in Arabidopsis thaliana and Oryza sativa

Transposable elements (TEs) are mobile genetic entities ubiquitously distributed in nearly all genomes.High frequency of codons ending in A/T in TEs has been previously observed in some species.In this study,the biases in nucleotide composition and codon usage of TE transposases and host nuclear genes were investigated in the AT-rich genome of Arabidopsis thaliana and the GC-rich genome of Oryza sativa.Codons ending in A/T are more frequently used by TEs compared with their host nuclear genes.A remarkable p...     

H1N1流感病毒聚合酶片段的CpG抑制及其对密码子偏爱性的影响

H1N1流感病毒的聚合酶具有RNA复制、转录等功能,并且对流感病毒片段包装、子代繁殖及宿主适应性等有着重要作用。通过分析人、猪及禽类H1N1流感病毒聚合酶片段的二核苷酸频率及同义密码子的偏爱性,发现不同宿主中,流感病毒聚合酶片段的CpG频率最低,且均被强烈抑制;通过三类宿主间的比较发现,人流感病毒抑制最为强烈,且其CpG频率随年份呈下降趋势,但2009年毒株的CpG频率突然上升。比较同义密码子使用频率发现,含有CpG的同义密码子相对使用频率均小于1,证明CpG抑制作用是影响同义密码子偏爱性的一个重要因素。以上结果暗示,CpG抑制对H1N1流感病毒的进化及跨宿主传播可能有重要影响。     

Codon bias and gene expression.

The frequencies with which individual synonymous codons are used to code their cognate amino acids is quite variable from genome to genome and within genomes, from gene to gene. One particularly well documented codon bias is that associated with highly expressed genes in bacteria as well as in yeast; this is the so-called major codon bias. Here, it is suggested that the major codon bias is not an arrangement for regulating individual gene expression. Instead, the data suggest that this codon bias, which is correlated with a corresponding bias of tRNA abundance, is a global arrangement for optimizing the growth efficiency of cells. On the practical side, it is suggested that heterologous gene expression is not as sensitive to codon bias as previously thought, but that it is quite sensitive to other characteristics of the heterologous gene.     

Codon usage bias covaries with expression breadth and the rate of synonymous evolution in humans, but this is not evidence for selection.

In numerous species, from bacteria to Drosophila, evidence suggests that selection acts even on synonymous codon usage: codon bias is greater in more abundantly expressed genes, the rate of synonymous evolution is lower in genes with greater codon bias, and there is consistency between genes in the same species in which codons are preferred. In contrast, in mammals, while nonequal use of alternative codons is observed, the bias is attributed to the background variance in nucleotide concentrations, reflected in the similar nucleotide composition of flanking noncoding and exonic third sites. However, a systematic examination of the covariants of codon usage controlling for background nucleotide content has yet to be performed. Here we present a new method to measure codon bias that corrects for background nucleotide content and apply this to 2396 human genes. Nearly all (99%) exhibit a higher amount of codon bias than expected by chance. The patterns associated with selectively driven codon bias are weakly recovered: Broadly expressed genes have a higher level of bias than do tissue-specific genes, the bias is higher for genes with lower rates of synonymous substitutions, and certain codons are repeatedly preferred. However, while these patterns are suggestive, the first two patterns appear to be methodological artifacts. The last pattern reflects in part biases in usage of nucleotide pairs. We conclude that we find no evidence for selection on codon usage in humans.     

Codon catalog usage and the genome hypothesis.

Frequencies for each of the 61 amino acid codons have been determined in every published mRNA sequence of 50 or more codons. The frequencies are shown for each kind of genome and for each individual gene. A surprising consistency of choices exists among genes of the same or similar genomes. Thus each genome, or kind of genome, appears to possess a "system" for choosing between codons. Frameshift genes, however, have widely different choice strategies from normal genes. Our work indicates that the main factors distinguishing between mRNA sequences relate to choices among degenerate bases. These systematic third base choices can therefore be used to establish a new kind of genetic distance, which reflects differences in coding strategy. The choice patterns we find seem compatible with the idea that the genome and not the individual gene is the unit of selection. Each gene in a genome tends to conform to its species' usage of the codon catalog; this is our genome hypothesis.