Factors affecting mito-nuclear codon usage interactions in the OXPHOS system of Drosophila melanogaster

Codon usage bias varies considerably among genomes and even within the genes of the same genome.In eukaryotic organisms,energy production in the form of oxidative phosphorylation(OXPHOS) is the only process under control of both nuclear and mitochondrial ge-nomes.Although factors affecting codon usage in a single genome have been studied,this has not occurred when both interactional ge-nomes are involved.Consequently,we investigated whether or not other factors influence codon usage of coevolved genes.We us...     

Evidence for a trade-off between translational efficiency and splicing regulation in determining synonymous codon usage in Drosophila melanogaster

In Drosophila melanogaster, synonymous codons corresponding to the most abundant cognate tRNAs are used more frequently, especially in highly expressed genes. Increased use of such "optimal" codons is considered an adaptation for translational efficiency. Need it always be the case that selection should favor the use of a translationally optimal codon? Here, we investigate one possible confounding factor, namely, the need to specify information in exons necessary to enable correct splicing. As expected from such a model, in Drosophila many codons show different usage near intron-exon boundaries versus exon core regions. However, this finding is in principle also consistent with Hill-Robertson effects modulating usage of translationally optimal codons. However, several results support the splice model over the translational selection model: 1) the trends in codon usage are strikingly similar to those in mammals in which codon usage near boundaries correlates with abundance in exonic splice enhancers (ESEs), 2) codons preferred near boundaries tend to be enriched for A and avoid C (conversely those avoided near boundaries prefer C rather than A), as expected were ESEs involved, and 3) codons preferred near boundaries are typically not translationally optimal. We conclude that usage of translationally optimal codons usage is compromised in the vicinity of splice junctions in intron-containing genes, to the effect that we observe higher levels of usage of translationally optimal codons at the center of exons. On the gene level, however, controlling for known correlates of codon bias, the impact on codon usage patterns is quantitatively small. These results have implications for inferring aspects of the mechanism of splicing given nothing more than a well-annotated genome.     

Selection on codon usage and base composition in Drosophila americana

We have used a polymorphism dataset on introns and coding sequences of X-linked loci in Drosophila americana to estimate the strength of selection on codon usage and/or biased gene conversion (BGC), taking into account a recent population expansion detected by a maximum-likelihood method. Drosophila americana was previously thought to have a stable demographic history, so that this evidence for a recent population expansion means that previous estimates of selection need revision. There was evidence for natural selection or BGC favouring GC over AT variants in introns, which is stronger for GC-rich than GC-poor introns. By comparing introns and coding sequences, we found evidence for selection on codon usage bias, which is much stronger than the forces acting on GC versus AT basepairs in introns.     

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。     

Origin and decay of the P element-associated latitudinal cline in Australian Drosophila melanogaster

The latitudinal cline in P transposable element-associated characteristics in eastern Australian populations of Drosophila melanogaster has changed between 1986 and 1991–1994. New collections were made in 1991–1994 from localities along the eastern coast of Australia. P element-associated properties of 256 isofemale lines from 43 localities were evaluated using gonadal dysgenesis and/or singed-weak hypermutability assays. The overall results indicate that both P activity and P susceptibility have declined, with all populations showing a tendency towards a state with little P activity potential but with P repressor function (neutral or ‘Q’). P repressor function is strong in all populations except some of the most southerly. P activity potential peaks at about 27° SLat, and drops off to the south (as in 1983–1986 collections) and to the north (in contrast to 1983–1986 collections); thus the cline is no longer a simple P-to-Q-to-M pattern from north to south, but is now Q-P-Q-M. A mtDNA RFLP that putatively distinguishes North American and European populations varies in frequency among the populations but the frequency does not vary clinally with latitude, ruling out massive introductions from North America and Europe as causing the cline. This revised version was published online in July 2006 with corrections to the Cover Date.     

我国大陆部分地区黑腹果蝇群体线粒体DNA多态性研究

用１０种限制性内切酶对我国大陆５个地方（武汉,长沙,桂林,南宁和北海）６个黑腹果蝇（Ｄｒｏｓｏｐｈｉｌａｍｅｌａｎｏｇａｓｔｅｒ）群体的线粒体ＤＮＡ进行了限制片段长度多态性分析,在５６个单雌系中,发同了２５种不同的限制类型,应用Ｎｅｉ等（１９７９）的数学模型和ＵＰＧ法,构建了限制类型间和群体间的系统进化树,结果发现：所研究的群体分为３个类群,对应于南,中和北３个亚热带地区,除长沙玉合醋厂外,所有采     

黑腹果蝇的性别控制

性别的形成包括两个过程,即性别决定和性别分化。果蝇的性别控制研究包括性别决定、性别分化、性别鉴定、性别诱导和性别控制5个方面。性别决定是在两种不同发育途径之间的选择,它提供了一个研究基因调控的模式系统。果蝇的性别决定问题已经研究得相当详细［1］。性别分化是使胚胎向着雌性或雄性发育的过程,决定了性别表型。果蝇的性别分化也取得了不少研究成果。近年来,许多重要的性别调控基因已被克隆和鉴定。随着果蝇基因组全序列测定的完成,果蝇的性别控制研究将会更为深入而完善。本文对与黑腹果蝇性别决定和性别分化相关的一些问题进行综述。     

Contrasting patterns of natural variation in global Drosophila melanogaster populations

Despite the popularity of Drosophila melanogaster in functional and evolutionary genetics, the global pattern of natural variation has not yet been comprehensively described in this species. For the first time, we report a combined survey using neutral microsatellites and mitochondrial sequence variation jointly. Thirty-five populations originating from five continents were compared. In agreement with previous microsatellite studies, sub-Saharan African populations were the most variable ones. Consistent with previous reports of a single 'out of Africa' habitat expansion, we found that non-African populations contained a subset of the African alleles. The pattern of variation detected for the mitochondrial sequences differed substantially. The most divergent haplotypes were detected in the Mediterranean region while Africa harboured most haplotypes, which were all closely related. In the light of the well-established African origin of D. melanogaster, our results cast severe doubts about the suitability of mtDNA for biogeographic inference in this model organism.     

Genetic variation affecting host-parasite interactions: major-effect quantitative trait loci affect the transmission of sigma virus in Drosophila melanogaster

In natural populations, genetic variation affects resistance to disease. Whether that genetic variation comprises lots of small-effect polymorphisms or a small number of large-effect polymorphisms has implications for adaptation, selection and how genetic variation is maintained in populations. Furthermore, how much genetic variation there is, and the genes that underlie this variation, affects models of co-evolution between parasites and their hosts. We are studying the genetic variation that affects the resistance of Drosophila melanogaster to its natural pathogen — the vertically transmitted sigma virus. We have carried out three separate quantitative trait locus mapping analyses to map gene variants on the second chromosome that cause variation in the rate at which males transmit the infection to their offspring. All three crosses identified a locus in a similar chromosomal location that causes a large drop in the rate at which the virus is transmitted. We also found evidence for an additional smaller-effect quantitative trait locus elsewhere on the chromosome. Our data, together with previous experiments on the sigma virus and parasitoid wasps, indicate that the resistance of D. melanogaster to co-evolved pathogens is controlled by a limited number of major-effect polymorphisms.     

Age-dependent behavior loss in adult Drosophila melanogaster

The use of Drosophila as an organism in which to study aging has been limited by the fact that few biomarkers of aging exist in the adult. In this paper we examine behavior loss relative to longevity in wild-type populations maintained at 22°C and 29°C to determine whether behavior loss—that is, loss of ability to perform certain innate behavioral responses within a defined test interval—can be used as biomarkers of aging. We find that under controlled conditions behavior loss can be used as a landmark of aging in populations maintained at either 22°C or 29°C. The ability to perform normal geotactic and phototactic responses is lost during the reproductive phase of the adult populations, whereas motor activity is not lost until well into the death phase. We feel that the use of behavior loss, together with other parameters of longevity in Drosophila, will allow comparisons to be made between different strains or between different environmental conditions to test their effect on aging. In the companion paper we demonstrate the use of behavior loss to identify a mutation which may accelerate the aging process.     

No evidence of mitochondrial genetic variation for sperm competition within a population of Drosophila melanogaster

Recent studies have advocated a role for mitochondrial DNA (mtDNA) in sperm competition. This is controversial because earlier theory and empirical work suggested that mitochondrial genetic variation for fitness is low. Yet, such studies dealt only with females and did not consider that variation that is neutral when expressed in females, might be non-neutral in males as, in most species, mtDNA is never selected in males. We measured male ability to compete for fertilizations, at young and late ages, across 25 cytoplasms expressed in three different nuclear genetic backgrounds, within a population of Drosophila melanogaster. We found no cytoplasmic (thus no mtDNA) genetic variation for either male offence or offensive sperm competitiveness. This contrasts with previous findings demonstrating cytoplasmic genetic variation for female fitness and female ageing across these same lines. Taken together, this suggests that mitochondrial genes do not contribute to variation in sperm competition at the within-population level.     

Simulation of gene pyramiding in Drosophila melanogaster

Gene pyramiding has been successfully practiced in plant breeding for developing new breeds or lines in which favorable genes from several different lines were integrated.But it has not been used in animal breeding,and some theoretical investigation and simulation analysis with respect to its strategies,feasibility and efficiency are needed before it can be implemented in animals.In this study,we used four different pure fines of Drosophila melanogaster,each of which is homozygous at a specific mutant gene with a visible effect on phenotype,to simulate the gene pyramiding process and analyze the duration and population size required in different pyramiding strategies.We finally got the ideal individuals,which are homozygous at the four target genes simultaneously.This study demonstrates that gene pyramiding is feasible in animal breeding and the interaction between genes may affect the final results.     

蓝莓花青素有效缓解种群拥挤对果蝇的胁迫

【目的】明确拥挤胁迫对果蝇生长发育的影响,并探讨蓝莓花青素(Blueberry anthocyanins,BAC)对黑腹果蝇Drosophila melanogaster Meigen拥挤损伤的保护作用。【方法】研究不同培养密度,BAC浓度及两者协同处理对果蝇生长发育、胁迫应激和氧化应激的影响。【结果】通过观察生长在低、中、高密度下的果蝇发现,随着培养密度的升高,果蝇的蛹历期延长,体重和雌雄比显著下降,HSP70的表达水平显著上升及MDA显著下降。BAC处理显著增加果蝇蛹的数量,缩短蛹历期,降低果蝇HSP70的表达和MDA含量。在高密度组果蝇培养基中添加维生素C(Vitamin C,VC)和BAC后,拥挤胁迫仍为主要影响因素,除了VC显著缓解果蝇雌雄比失衡外,两种药物对果蝇体重和蛹历期的恢复均无显著效应。但VC和BAC处理显著降低果蝇HSP70的表达水平和MDA含量,VC处理显著提高CAT和SOD酶活性,而BAC对酶活性的影响小。雌蝇对拥挤胁迫更敏感,因此,高密度下VC和BAC对雌蝇的影响比雄蝇大。【结论】拥挤胁迫导致果蝇发育延缓,体重下降,雌雄比失衡,这与其激发果蝇的应激反应和氧化损伤相关,VC和BAC能够降低拥挤胁迫诱导的应激反应,减少氧化损伤。     

Simulation of gene pyramiding in Drosophila melanogaster

Gene pyramiding has been successfully practiced in plant breeding for developing new breeds or lines in which favorable genes from several different lines were integrated.But it has not been used in animal breeding,and some theoretical investigation and simulation analysis with respect to its strategies,feasibility and efficiency are needed before it can be implemented in animals.In this study,we used four different pure lines of Drosophila melanogaster,each of which is homozygous at a specific mutant gene ...     

Factors influencing the synonymous codon and amino acid usage bias in AT-rich Pseudomonas aeruginosa phage PhiKZ

To reveal how the AT-rich genome of bacteriophage PhiKZ has been shaped in order to carryout its growth in the GC-rich host Pseudomonas aeruginosa,synonymous codon and amino acid usage bias ofPhiKZ was investigated and the data were compared with that of P.aeruginosa.It was found that synonymouscodon and amino acid usage of PhiKZ was distinct from that of P.aeruginosa.In contrast to P.aeruginosa,the third codon position of the synonymous codons of PhiKZ carries mostly A or T base;codon usage biasin PhiKZ is dictated mainly by mutational bias and,to a lesser extent,by translational selection.A clusteranalysis of the relative synonymous codon usage values of 16 myoviruses including PhiKZ shows that PhiKZis evolutionary much closer to Escherickia coli phage T4.Further analysis reveals that the three factors ofmean molecular weight,aromaticity and cysteine content are mostly responsible for the variation of aminoacid usage in PhiKZ proteins,whereas amino acid usage of P.aeruginosa proteins is mainly governed bygrand average of hydropathicity,aromaticity and cysteine content.Based on these observations,we suggestthat codons of the phage-like PhiKZ have evolved to preferentially incorporate the smaller amino acid residuesinto their proteins during translation,thereby economizing the cost of its development in GC-rich P.aeruginosa.     

Patterns of codon usage in two ciliates that reassign the genetic code: Tetrahymena thermophila and Paramecium tetraurelia

We used the recently sequenced genomes of the ciliates Tetrahymena thermophila and Paramecium tetraurelia to analyze the codon usage patterns in both organisms; we have analyzed codon usage bias, Gln codon usage, GC content and the nucleotide contexts of initiation and termination codons in Tetrahymena and Paramecium. We also studied how these trends change along the length of the genes and in a subset of highly expressed genes. Our results corroborate some of the trends previously described in Tetrahymena, but also negate some specific observations. In both genomes we found a strong bias toward codons with low GC content; however, in highly expressed genes this bias is smaller and codons ending in GC tend to be more frequent. We also found that codon bias increases along gene segments and in highly expressed genes and that the context surrounding initiation and termination codons are always AT rich. Our results also suggest differences in the efficiency of translation of the reassigned stop codons between the two species and between the reassigned codons. Finally, we discuss some of the possible causes for such translational efficiency differences.     

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 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.     

Factors affecting codon bias in the mitochondrial genomes of the streptophyte Mesostigma viride and the chlorophyte Chlamydomonas reinhardtii

Mitochondrial genomes typically show genome-wide patterns of synonymous codon usage bias. In animals and land plants, mutation appears more dominant than selection in shaping this bias, while in green algae the relative importance of these factors is not well studied. Based on our analysis of mitochondrial DNA sequence from the green algae Mesostigma viride (NIES-296) and Chlamydomonas reinhardtii (CC-277) and a closely related relative of each, we conclude that both mutation and selection are important in shaping synonymous codon usage bias in their mitochondrial genomes, with selection being more dominant. The possible confounding influence of mutational context dependence on our analyses is discussed.