Codon Usage Differences among Genes Expressed in Different Tissues of Drosophila melanogaster.
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ABSTRACT:
SUBMITTER: Payne BL
PROVIDER: S-EPMC6456009 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Severe acute respiratory syndrome has spread quickly throughout the world and was declared a pandemic by the World Health Organization (WHO). The pathogenic agent is a new coronavirus (SARS-CoV-2) that infects pulmonary cells with great effectiveness. In this study we focus on the codon composition for the viral protein synthesis and its relationship with the protein synthesis of the host. Our analysis reveals that SARS-CoV-2 preferred codons have poor representation of G or C nucleotides in the third position, a characteristic which could result in an unbalance in the tRNAs pools of the infected cells with serious implications in host protein synthesis. By integrating this observation with proteomic data from infected cells, we observe a reduced translation rate of host proteins associated with highly expressed genes and that they share the codon usage bias of the virus. The functional analysis of these genes suggests that this mechanism of epistasis can contribute to understanding how this virus evades the immune response and the etiology of some deleterious collateral effect as a result of the viral replication. In this manner, our finding contributes to the understanding of the SARS-CoV-2 pathogeny and could be useful for the design of a vaccine based on the live attenuated strategy.
| S-EPMC7468442 | biostudies-literature
Project description:Although the genetic code is redundant, synonymous codons for the same amino acid are not used with equal frequencies in genomes, a phenomenon termed "codon usage bias." Previous studies have demonstrated that synonymous changes in a coding sequence can exert significant cis effects on the gene's expression level. However, whether the codon composition of a gene can also affect the translation efficiency of other genes has not been thoroughly explored. To study how codon usage bias influences the cellular economy of translation, we massively converted abundant codons to their rare synonymous counterpart in several highly expressed genes in Escherichia coli This perturbation reduces both the cellular fitness and the translation efficiency of genes that have high initiation rates and are naturally enriched with the manipulated codon, in agreement with theoretical predictions. Interestingly, we could alleviate the observed phenotypes by increasing the supply of the tRNA for the highly demanded codon, thus demonstrating that the codon usage of highly expressed genes was selected in evolution to maintain the efficiency of global protein translation.
| S-EPMC6003480 | biostudies-literature
Project description:Codon usage bias affects the genomes of organisms from all kingdoms of life and results from both background substitution biases and natural selection. Natural selection on codon usage to increase translation accuracy and efficiency has long been known to affect gene sequences. Such selection is stronger on highly, compared with lowly expressed genes, resulting in higher levels of codon bias within genes with higher expression levels. Additionally, selection on translation accuracy affects more strongly codons encoding conserved amino acids, since these will more often affect protein folding and/or function. By applying tests of selection on the gene sequences of the bacterium Escherichia coli, we demonstrate that both highly and lowly expressed genes display signals of selection on codon usage. Such signals are found for both conserved and less conserved amino acid positions, even within the 10% of E. coli genes expressed at the lowest levels. We further demonstrate experimentally that single synonymous codon replacements within a lowly expressed, essential gene can carry substantial effects on bacterial fitness. Combined, our results demonstrate that even within genes expressed at relatively low levels there is substantial selection on codon usage and that single synonymous codon replacements within such genes can have a marked effect on bacterial fitness.
| S-EPMC5961134 | biostudies-literature
Project description:Codon usage bias (CUB), where certain codons are used more frequently than expected by chance, is a ubiquitous phenomenon and occurs across the tree of life. The dominant paradigm is that the proportion of preferred codons is set by weak selection. While experimental changes in codon usage have at times shown large phenotypic effects in contrast to this paradigm, genome-wide population genetic estimates have supported the weak selection model. Here we use deep genomic population sequencing of two Drosophila melanogaster populations to measure selection on synonymous sites in a way that allowed us to estimate the prevalence of both weak and strong purifying selection. We find that selection in favor of preferred codons ranges from weak (|Nes| ∼ 1) to strong (|Nes| > 10), with strong selection acting on 10-20% of synonymous sites in preferred codons. While previous studies indicated that selection at synonymous sites could be strong, this is the first study to detect and quantify strong selection specifically at the level of CUB. Further, we find that CUB-associated polymorphism accounts for the majority of strong selection on synonymous sites, with secondary contributions of splicing (selection on alternatively spliced genes, splice junctions, and spliceosome-bound sites) and transcription factor binding. Our findings support a new model of CUB and indicate that the functional importance of CUB, as well as synonymous sites in general, have been underestimated.
| S-EPMC7017021 | biostudies-literature
Project description:Male-derived accessory gland proteins that are transferred to females during mating have profound effects on female reproductive physiology including increased ovulation, mating inhibition, and effects on sperm utilization and storage. The extreme rates of evolution seen in accessory gland proteins may be driven by sperm competition and sexual conflict, processes that may ultimately drive complex interactions between female- and male-derived molecules and sperm. However, little is known of how gene expression in female reproductive tissues changes in response to the presence of male molecules and sperm. To characterize this response, we conducted parallel genomic and proteomic analyses of gene expression in the reproductive tract of 3-day-old unmated and mated female Drosophila melanogaster. Using DNA microarrays, we identified 539 transcripts that are differentially expressed in unmated vs. mated females and revealed a striking peak in differential expression at 6 h postmating and a marked shift from primarily down-regulated to primarily up-regulated transcripts within 3 h after mating. Combining two-dimensional gel electrophoresis and liquid chromatography mass spectrometry analyses, we identified 84 differentially expressed proteins at 3 h postmating, including proteins that appeared to undergo posttranslational modification. Together, our observations define transcriptional and translational response to mating within the female reproductive tract and suggest a bimodal model of postmating gene expression initially correlated with mating and the final stages of female reproductive tract maturation and later with the declining presence of male reproductive molecules and with sperm maintenance and utilization.
| S-EPMC1502462 | biostudies-literature
Project description:Codon usage bias (CUB) in Drosophila is higher for X-linked genes than for autosomal genes. One possible explanation is that the higher effective recombination rate for genes on the X chromosome compared with the autosomes reduces their susceptibility to Hill-Robertson effects, and thus enhances the efficacy of selection on codon usage. The genome sequence of D. melanogaster was used to test this hypothesis. Contrary to expectation, it was found that, after correcting for the effective recombination rate, CUB remained higher on the X than on the autosomes. In contrast, an analysis of polymorphism data from a Rwandan population showed that mean nucleotide site diversity at 4-fold degenerate sites for genes on the X is approximately three-quarters of the autosomal value after correcting for the effective recombination rate, compared with approximate equality before correction. In addition, these data show that selection for preferred versus unpreferred synonymous variants is stronger on the X than the autosomes, which accounts for the higher CUB of genes on the X chromosome. This difference in the strength of selection does not appear to reflect the effects of dominance of mutations affecting codon usage, differences in gene expression levels between X and autosomes, or differences in mutational bias. Its cause therefore remains unexplained. The stronger selection on CUB on the X chromosome leads to a lower rate of synonymous site divergence compared with the autosomes; this will cause a stronger upward bias for X than A in estimates of the proportion of nonsynonymous mutations fixed by positive selection, for methods based on the McDonald-Kreitman test.
| S-EPMC3603305 | biostudies-literature
Project description:Codon usage bias (CUB), the uneven use of synonymous codons, is a ubiquitous observation in virtually all organisms examined. The pattern of codon usage is generally similar among closely related species, but differs significantly among distantly related organisms, e.g., bacteria, yeast, and Drosophila. Several explanations for CUB have been offered and some have been supported by observations and experiments, although a thorough understanding of the evolutionary forces (random drift, mutation bias, and selection) and their relative importance remains to be determined. The recently available complete genome DNA sequences of twelve phylogenetically defined species of Drosophila offer a hitherto unprecedented opportunity to examine these problems. We report here the patterns of codon usage in the twelve species and offer insights on possible evolutionary forces involved.(1) Codon usage is quite stable across 11/12 of the species: G- and especially C-ending codons are used most frequently, thus defining the preferred codons. (2) The only amino acid that changes in preferred codon is Serine with six species of the melanogaster group favoring TCC while the other species, particularly subgenus Drosophila species, favor AGC. (3) D. willistoni is an exception to these generalizations in having a shifted codon usage for seven amino acids toward A/T in the wobble position. (4) Amino acids differ in their contribution to overall CUB, Leu having the greatest and Asp the least. (5) Among two-fold degenerate amino acids, A/G ending amino acids have more selection on codon usage than T/C ending amino acids. (6) Among the different chromosome arms or elements, genes on the non-recombining element F (dot chromosome) have the least CUB, while genes on the element A (X chromosome) have the most. (7) Introns indicate that mutation bias in all species is approximately 2:1, AT:GC, the opposite of codon usage bias. (8) There is also evidence for some overall regional bias in base composition that may influence codon usage.Overall, these results suggest that natural selection has acted on codon usage in the genus Drosophila, at least often enough to leave a footprint of selection in modern genomes. However, there is evidence in the data that random forces (drift and mutation) have also left patterns in the data, especially in genes under weak selection for codon usage for example genes in regions of low recombination. The documentation of codon usage patterns in each of these twelve genomes also aids in ongoing annotation efforts.
| S-EPMC2213667 | biostudies-literature
Project description:BACKGROUND:Polyomaviruses (PyVs) have a wide range of hosts, from humans to fish, and their effects on hosts vary. The differences in the infection characteristics of PyV with respect to the host are assumed to be influenced by the biochemical function of the LT-Ag protein, which is related to the cytopathic effect and tumorigenesis mechanism via interaction with the host protein. METHODS:We carried out a comparative analysis of codon usage patterns of large T-antigens (LT-Ags) of PyVs isolated from various host species and their functional domains and sequence motifs. Parity rule 2 (PR2) and neutrality analysis were applied to evaluate the effects of mutation and selection pressure on codon usage bias. To investigate evolutionary relationships among PyVs, we carried out a phylogenetic analysis, and a correspondence analysis of relative synonymous codon usage (RSCU) values was performed. RESULTS:Nucleotide composition analysis using LT-Ag gene sequences showed that the GC and GC3 values of avian PyVs were higher than those of mammalian PyVs. The effective number of codon (ENC) analysis showed host-specific ENC distribution characteristics in both the LT-Ag gene and the coding sequences of its domain regions. In the avian and fish PyVs, the codon diversity was significant, whereas the mammalian PyVs tended to exhibit conservative and host-specific evolution of codon usage bias. The results of our PR2 and neutrality analysis revealed mutation bias or highly variable GC contents by showing a narrow GC12 distribution and wide GC3 distribution in all sequences. Furthermore, the calculated RSCU values revealed differences in the codon usage preference of the LT-AG gene according to the host group. A similar tendency was observed in the two functional domains used in the analysis. CONCLUSIONS:Our study showed that specific domains or sequence motifs of various PyV LT-Ags have evolved so that each virus protein interacts with host cell targets. They have also adapted to thrive in specific host species and cell types. Functional domains of LT-Ag, which are known to interact with host proteins involved in cell proliferation and gene expression regulation, may provide important information, as they are significantly related to the host specificity of PyVs.
| S-EPMC6854729 | biostudies-literature
Project description:Recently, the phenomenon of clustering of co-expressed genes on chromosomes was discovered in eukaryotes. To explore the hypothesis that genes within clusters occupy shared chromatin domains, we performed a detailed analysis of transcription pattern and chromatin structure of a cluster of co-expressed genes. We found that five non-homologous genes (Crtp, Yu, CK2betates, Pros28.1B and CG13581) are expressed exclusively in Drosophila melanogaster male germ-line and form a non-interrupted cluster in the 15 kb region of chromosome 2. The cluster is surrounded by genes with broader transcription patterns. Analysis of DNase I sensitivity revealed 'open' chromatin conformation in the cluster and adjacent regions in the male germ-line cells, where all studied genes are transcribed. In contrast, in somatic tissues where the cluster genes are silent, the domain of repressed chromatin encompassed four out of five cluster genes and an adjacent non-cluster gene CG13589 that is also silent in analyzed somatic tissues. The fifth cluster gene (CG13581) appears to be excluded from the chromatin domain occupied by the other four genes. Our results suggest that extensive clustering of co-expressed genes in eukaryotic genomes does in general reflect the domain organization of chromatin, although domain borders may not exactly correspond to the margins of gene clusters.
| S-EPMC1062873 | biostudies-literature
Project description:BackgroundSPANX (sperm protein coupled with the nucleus in the X chromosome) genes play a crucial role in human spermatogenesis. Codon usage bias (CUB) is a well-known phenomenon that exists in many genomes and mainly determined by mutation and selection. CUB is species specific and a unique characteristic of a genome. Analysis of compositional features and codon usage pattern of SPANX genes in human has contributed to explore the molecular biology of this gene. In our current study, we have retrieved the sequences of different variants of SPANX gene from NCBI using accession number and a perl script was used to analyze the nucleotide composition and the parameters for codon usage bias.ResultsOur results showed that codon usage bias is low as measured by codon bias index (CBI) and most of the GC ending codons were positively correlated with GC bias as indicated by GC3. That mutation pressure and natural selection affect the codon usage pattern were revealed by correspondence analysis (COA) and neutrality plot. Moreover, the neutrality plot further suggested that the role of natural selection is higher than mutation pressure on SPANX genes.ConclusionsThe codon usage bias in SPANX genes is not very high and the role of natural selection dominates over mutation pressure in the codon usage of human SPANX genes.
| S-EPMC4658643 | biostudies-literature