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Tripathy, Sucheta, and Brett M. Tyler. "The Repertoire of Transfer RNA Genes Is Tuned to Codon Usage Bias in the Genomes of Phytophthora sojae and Phytophthora ramorum." Molecular Plant-Microbe Interactions® 19, no. 12 (2006): 1322–28. http://dx.doi.org/10.1094/mpmi-19-1322.
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In all, 238 and 155 transfer (t)RNA genes were predicted from the genomes of Phytophthora sojae and P. ramorum, respectively. After omitting pseudogenes and undetermined types of tRNA genes, there remained 208 P. sojae tRNA genes and 140 P. ramorum tRNA genes. There were 45 types of tRNA genes, with distinct anticodons, in each species. Fourteen common anticodon types of tRNAs are missing altogether from the genome in the two species; however, these appear to be compensated by wobbling of other tRNA anticodons in a manner which is tied to the codon bias in Phytophthora genes. The most abundant tRNA class was arginine in both P. sojae and P. ramorum. A codon usage table was generated for these two organisms from a total of 9,803,525 codons in P. sojae and 7,496,598 codons in P. ramorum. The most abundant codon type detected from the codon usage tables was GAG (encoding glutamic acid), whereas the most numerous tRNA gene had a me-thionine anticodon (CAT). The correlation between the frequencies of tRNA genes and the codon frequencies in protein-coding genes was very low (0.12 in P. sojae and 0.19 in P. ramorum); however, the correlation between amino acid tRNA gene frequency and the corresponding amino acid codon frequency in P. sojae and P. ramorum was substantially higher (0.53 in P. sojae and 0.77 in P. ramorum). The codon usage frequencies of P. sojae and P. ramorum were very strongly correlated (0.99), as were tRNA gene frequencies (0.77). Approximately 60% of orthologous tRNA gene pairs in P. sojae and P. ramorum are located in regions that have conserved synteny in the two species.
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Zaytsev, Konstantin, Natalya Bogatyreva, and Alexey Fedorov. "Link Between Individual Codon Frequencies and Protein Expression: Going Beyond Codon Adaptation Index." International Journal of Molecular Sciences 25, no. 21 (2024): 11622. http://dx.doi.org/10.3390/ijms252111622.
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An important role of a particular synonymous codon composition of a gene in its expression level is well known. There are a number of algorithms optimizing codon usage of recombinant genes to maximize their expression in host cells. Nevertheless, the underlying mechanism remains unsolved and is of significant relevance. In the realm of modern biotechnology, directing protein production to a specific level is crucial for metabolic engineering, genome rewriting and a growing number of other applications. In this study, we propose two new simple statistical and empirical methods for predicting the protein expression level from the nucleotide sequence of the corresponding gene: Codon Expression Index Score (CEIS) and Codon Productivity Score (CPS). Both of these methods are based on the influence of each individual codon in the gene on the overall expression level of the encoded protein and the frequencies of isoacceptors in the species. Our predictions achieve a correlation level of up to r = 0.7 with experimentally measured quantitative proteome data of Escherichia coli, which is superior to any previously proposed methods. Our work helps understand how codons determine protein abundances. Based on these methods, it is possible to design proteins optimized for expression in a particular organism.
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Belin, Dominique, and Pere Puigbò. "Why Is the UAG (Amber) Stop Codon Almost Absent in Highly Expressed Bacterial Genes?" Life 12, no. 3 (2022): 431. http://dx.doi.org/10.3390/life12030431.
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The genome hypothesis postulates that genes in a genome tend to conform to their species’ usage of the codon catalog and the GC content of the DNA. Thus, codon frequencies differ across organisms, including the three termination codons in the standard genetic code. Here, we analyze the frequencies of stop codons in a group of highly expressed genes from 196 prokaryotes under strong translational selection. The occurrence of the three translation termination codons is highly biased, with UAA (ochre) being the most prevalent in almost all bacteria. In contrast, UAG (amber) is the least frequent termination codon, e.g., only 321 occurrences (7.4%) in E. coli K-12 substr. W3110. Of the 253 highly expressed genes, only two end with an UAG codon. The strength of the selective bias against UAG in highly expressed genes varies among bacterial genomes, but it is not affected by the GC content of these genomes. In contrast, increased GC content results in a decrease in UAA abundance with a concomitant increase in UGA abundance. We propose that readthrough efficiency and context effects could explain the prevalence of UAA over UAG, particularly in highly expressed genes. Findings from this communication can be utilized for the optimization of gene expression.
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Yu, Zeyue. "Codon usage bias analysis of 22 Anemone." Highlights in Science, Engineering and Technology 102 (July 11, 2024): 328–37. http://dx.doi.org/10.54097/04rwse67.
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Codon preference analysis for the rbcL gene of Ranunculaceae plants remains to be completed, and for this purpose we selected 10801 codons from 23 Ranunculaceae Juss. plants for analysis. Among them, 30 codons had relative synonymous codon usage values greater than or equal to 1. The codon endings were preferred to A and U, among which U was more preferred. Neutrality plot analysis, ENC-GC3s plot analysis and PR2 bias plot analysis showed that codon preference in Anemone L. was mainly influenced by selection pressure. Cluster analysis showed that a phylogenetic tree could be constructed for Anemone L. based on relative synonymous codon usage values. Comparison with codon usage frequencies in model organisms indicated that Arabidopsis thaliana and Saccharomyces cerevisiae are more suitable vectors for exogenous expression of the rbcL gene in Anemone L. plants. These results help to elucidate the molecular biological characteristics of Ranunculaceae Juss. plants for further exploitation of Ranunculaceae Juss. plant resources in areas such as synthetic biology.
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Yuzbasiyan-Gurkan, Vilma, Janver D. Krehbiel, Yueying Cao, and Patrick J. Venta. "Development and usefulness of new polymerase chain reaction-based tests for detection of different alleles at codons 136 and 171 of the ovine prion protein gene." American Journal of Veterinary Research 60, no. 7 (1999): 884–87. http://dx.doi.org/10.2460/ajvr.1999.60.07.884.
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Abstract Objective To develop new and improved tests to detect alleles at codons 136 and 171 of the ovine prion protein locus and to evaluate the frequency of these alleles. Animals 159 Suffolk sheep belonging to 3 flocks. Procedure Polymerase chain reaction (PCR) analysis that contained diagnostic restriction site variation for each allele were developed for the relevant gene regions. Alleles were determined by analyzing DNA isolated from buccal swab specimens or blood samples. Results At codon 136, frequencies of the alanine and valine alleles were found to be 97 and 3%, respectively. At codon 171, frequencies of the glutamine, arginine, and histidine alleles were found to be 57, 41, and 2%, respectively. Conclusions Little variation was detected in codon 136, whereas noteworthy variation was found in codon 171; > 40% of the alleles at this locus coded for glutamine. Because the glutamine allele at codon 171 confers susceptibility to scrapie, reduction of its frequency is of importance to management of sheep flocks. Clinical Relevance Genotyping of sheep, using the tests reported here, should facilitate selective breeding programs designed to decrease the risk of scrapie. (Am J Vet Res 1999;60:884–887)
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Khomtchouk, Bohdan B., and Wolfgang Nonner. "Gaussian-Distributed Codon Frequencies of Genomes." G3: Genes|Genomes|Genetics 9, no. 5 (2019): 1449–56. http://dx.doi.org/10.1534/g3.118.200939.
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Frumkin, Idan, Marc J. Lajoie, Christopher J. Gregg, Gil Hornung, George M. Church, and Yitzhak Pilpel. "Codon usage of highly expressed genes affects proteome-wide translation efficiency." Proceedings of the National Academy of Sciences 115, no. 21 (2018): E4940—E4949. http://dx.doi.org/10.1073/pnas.1719375115.
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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 significantciseffects 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 inEscherichia 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.
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Burns, Cara C., Ray Campagnoli, Jing Shaw, Annelet Vincent, Jaume Jorba, and Olen Kew. "Genetic Inactivation of Poliovirus Infectivity by Increasing the Frequencies of CpG and UpA Dinucleotides within and across Synonymous Capsid Region Codons." Journal of Virology 83, no. 19 (2009): 9957–69. http://dx.doi.org/10.1128/jvi.00508-09.
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ABSTRACT Replicative fitness of poliovirus can be modulated systematically by replacement of preferred capsid region codons with synonymous unpreferred codons. To determine the key genetic contributors to fitness reduction, we introduced different sets of synonymous codons into the capsid coding region of an infectious clone derived from the type 2 prototype strain MEF-1. Replicative fitness in HeLa cells, measured by plaque areas and virus yields in single-step growth experiments, decreased sharply with increased frequencies of the dinucleotides CpG (suppressed in higher eukaryotes and most RNA viruses) and UpA (suppressed nearly universally). Replacement of MEF-1 capsid codons with the corresponding codons from another type 2 prototype strain (Lansing), a randomization of MEF-1 synonymous codons, increased the %G+C without increasing CpG, and reductions in the effective number of codons used had much smaller individual effects on fitness. Poliovirus fitness was reduced to the threshold of viability when CpG and UpA dinucleotides were saturated within and across synonymous codons of a capsid region interval representing only ∼9% of the total genome. Codon replacements were associated with moderate decreases in total virion production but large decreases in the specific infectivities of intact poliovirions and viral RNAs. Replication of codon replacement viruses, but not MEF-1, was temperature sensitive at 39.5°C. Synthesis and processing of viral intracellular proteins were largely unaltered in most codon replacement constructs. Replacement of natural codons with synonymous codons with increased frequencies of CpG and UpA dinucleotides may offer a general approach to the development of attenuated vaccines with well-defined antigenicities and very high genetic stabilities.
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Wolstenholme, David R., and Douglas O. Clary. "SEQUENCE EVOLUTION OF DROSOPHILA MITOCHONDRIAL DNA." Genetics 109, no. 4 (1985): 725–44. http://dx.doi.org/10.1093/genetics/109.4.725.
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ABSTRACT We have compared nucleotide sequences of corresponding segments of the mitochondrial DNA (mtDNA) molecules of Drosophila yakuba and Drosophila melanogaster, which contain the genes for six proteins and seven tRNAs. The overall frequency of substitution between the nucleotide sequences of these protein genes is 7.2%. As was found for mtDNAs from closely related mammals, most substitutions (86%) in Drosophila mitochondrial protein genes do not result in an amino acid replacement. However, the frequencies of transitions and transversions are approximately equal in Drosophila mtDNAs, which is in contrast to the vast excess of transitions over transversions in mammalian mtDNAs. In Drosophila mtDNAs the frequency of C ↔ T substitutions per codon in the third position is 2.5 times greater among codons of two-codon families than among codons of four-codon families; this is contrary to the hypothesis that third position silent substitutions are neutral in regard to selection. In the third position of codons of four-codon families transversions are 4.6 times more frequent than transitions and A ↔ T substitutions account for 86% of all transversions. Ninety-four percent of all codons in the Drosophila mtDNA segments analyzed end in A or T. However, as this alone cannot account for the observed high frequency of A ↔ T substitutions there must be either a disproportionately high rate of A ↔ T mutation in Drosophila mtDNA or selection bias for the products of A ↔ T mutation.—Consideration of the frequencies of interchange of AGA and AGT codons in the corresponding D. yakuba and D. melanogaster mitochondrial protein genes provides strong support for the view that AGA specifies serine in the Drosophila mitochondrial genetic code.
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Mazumder, G. A., A. Uddin, and S. Chakraborty. "Expression levels and codon usage patterns in nuclear genes of the filarial nematodeWucheraria bancroftiand the blood flukeSchistosoma haematobium." Journal of Helminthology 91, no. 1 (2016): 72–79. http://dx.doi.org/10.1017/s0022149x16000092.
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AbstractSynonymous codons are used with different frequencies, a phenomenon known as codon bias, which exists in many genomes and is mainly resolute by mutation and selection. To elucidate the genetic characteristics and evolutionary relationship ofWucheraria bancroftiandSchistosoma haematobiumwe examined the pattern of synonymous codon usage in nuclear genes of both the species. The mean overall GC contents ofW. bancroftiandS. haematobiumwere 43.41 and 36.37%, respectively, which suggests that genes in both the species were AT rich. The value of the High Effective Number of Codons in both species suggests that codon usage bias was weak. Both species had a wide range of P3 distribution in the neutrality plot, with a significant correlation between P12 and P3. The codons were closer to the axes in correspondence analysis, suggesting that mutation pressure influenced the codon usage pattern in these species. We have identified the more frequently used codons in these species, most codons ending with an A or T. The nucleotides A/T and C/G were not proportionally used at the third position of codons, which reveals that natural selection might influence the codon usage patterns. The regression equation of P12 on P3 suggests that natural selection might have played a major role, while mutational pressure played a minor role in codon usage pattern in both species. These results form the basis of exploring the evolutionary mechanisms and the heterologous expression of medically important proteins ofW. bancroftiandS. haematobium.
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Korkmaz, Gürkan, Mikael Holm, Tobias Wiens, and Suparna Sanyal. "Comprehensive Analysis of Stop Codon Usage in Bacteria and Its Correlation with Release Factor Abundance." Journal of Biological Chemistry 289, no. 44 (2014): 30334–42. http://dx.doi.org/10.1074/jbc.m114.606632.
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We present a comprehensive analysis of stop codon usage in bacteria by analyzing over eight million coding sequences of 4684 bacterial sequences. Using a newly developed program called “stop codon counter,” the frequencies of the three classical stop codons TAA, TAG, and TGA were analyzed, and a publicly available stop codon database was built. Our analysis shows that with increasing genomic GC content the frequency of the TAA codon decreases and that of the TGA codon increases in a reciprocal manner. Interestingly, the release factor 1-specific codon TAG maintains a more or less uniform frequency (∼20%) irrespective of the GC content. The low abundance of TAG is also valid with respect to expression level of the genes ending with different stop codons. In contrast, the highly expressed genes predominantly end with TAA, ensuring termination with either of the two release factors. Using three model bacteria with different stop codon usage (Escherichia coli, Mycobacterium smegmatis, and Bacillus subtilis), we show that the frequency of TAG and TGA codons correlates well with the relative steady state amount of mRNA and protein for release factors RF1 and RF2 during exponential growth. Furthermore, using available microarray data for gene expression, we show that in both fast growing and contrasting biofilm formation conditions, the relative level of RF1 is nicely correlated with the expression level of the genes ending with TAG.
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Velazquez-Hernandez, Nadia, Cosme Alvarado-Esquivel, Brissia Lazalde-Medina, et al. "Lack of Association between Mannose-binding Lectin 2 Codons 54 and 57 Gene Polymorphisms and Cervicovaginal Infections in Mexican Women." International Journal of Biomedical Science 13, no. 2 (2017): 79–83. http://dx.doi.org/10.59566/ijbs.2017.13079.
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The mannose-binding lectin (MBL) 2 gene has an important function in the innate immune response and activation of the third pathway of the complement system. Some studies have assessed the association of the MBL2 gene polymorphisms with cervicovaginal infections (CVI); however, there is no information about this association in Mexican women. This study aimed to determine the association between the MBL2 codons 54 and 57 gene polymorphisms with CVI in a sample of Mexican women. Through a cross-sectional study, blood samples and cervicovaginal cultures were obtain from 354 women. MBL2 genotyping was performed by real-time polymerase chain reaction with Taqman probes. Of the 354 women studied, 128 (36.2%) had CVI and 226 (63.8%) were healthy. The frequencies of the C and T variants in codon 54 in women with CVI were 83% and 17%, respectively; whereas the frequencies of these variants in healthy women were 82% and 18%, respectively. The frequencies of variants C/C, C/T, and T/T in women with CVI were 68%, 31%, and 1%, respectively; whereas the frequencies of these variants in healthy women were 68%, 29%, and 3%, respectively. With respect to codon 57, the frequencies of variants C and T were identical in women with CVI and in healthy women (97% and 3%, respectively). The frequencies of variants C/C, C/T, and T/T were identical in women with CVI and in healthy women (94%, 6%, and 0%, respectively). We conclude that MBL2 codons 54 and 57 gene polymorphisms do not associate with CVI in Mexican women.
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Zabavnik, Jelka, Marko Cotman, Polona Juntes, and Ivan Ambrozic. "A decade of using small-to-medium throughput allele discrimination assay to determine prion protein gene (Prnp) genotypes in sheep in Slovenia." Journal of Veterinary Diagnostic Investigation 30, no. 1 (2017): 144–49. http://dx.doi.org/10.1177/1040638717723946.
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Sheep with valine (V) at codon 136 and glutamine (Q) at codon 171 of the prion protein gene ( Prnp) are highly susceptible to classical scrapie, whereas phenylalanine (F) at codon 141 and histidine (H) at codon 154 play a major role in the susceptibility to atypical scrapie. A TaqMan real-time PCR assay was developed to determine Prnp alleles at codons 136, 141, 154, and 171 and used in classical scrapie eradication and breeding programs adopted in Slovenia. The frequency of the most resistant genotypes ARR/ARR and ARR/ARQ increased significantly in tested animals ( n = 35,138) from 6.7 and 27.1% of the tested sheep in 2006 to 12.1 and 32.4%, respectively, in 2015. Frequencies of more susceptible genotypes ARQ/ARQ and ARQ/VRQ decreased significantly from 36.4 and 3.5% in 2006 to 31.1 and 1.8%, respectively, in 2015. The most susceptible genotype VRQ/VRQ was detected in <0.5% of tested sheep. Frequencies of alleles AFRQ and AHQ affecting the susceptibility to atypical scrapie did not change significantly. The developed assay was suitable for genotyping on a small-to-medium throughput scale and was successfully used in classical scrapie eradication, as well as for the selection of classical scrapie–resistant sheep within breeding programs in Slovenia.
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Yang, Xiaoming, Yuan Wang, Wenxuan Gong, and Yinxiang Li. "Comparative Analysis of the Codon Usage Pattern in the Chloroplast Genomes of Gnetales Species." International Journal of Molecular Sciences 25, no. 19 (2024): 10622. http://dx.doi.org/10.3390/ijms251910622.
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Codon usage bias refers to the preferential use of synonymous codons, a widespread phenomenon found in bacteria, plants, and animals. Codon bias varies among species, families, and groups within kingdoms and between genes within an organism. Codon usage bias (CUB) analysis sheds light on the evolutionary dynamics of various species and optimizes targeted gene expression in heterologous host plants. As a significant order of gymnosperms, species within Gnetales possess extremely high ecological and pharmaceutical values. However, comprehensive analyses of CUB within the chloroplast genomes of Gnetales species remain unexplored. A systematic analysis was conducted to elucidate the codon usage patterns in 13 diverse Gnetales species based on the chloroplast genomes. Our results revealed that chloroplast coding sequences (cp CDSs) in 13 Gnetales species display a marked preference for AT bases and A/T-ending codons. A total of 20 predominantly high-frequency codons and between 2 and 7 optimal codons were identified across these species. The findings from the ENC-plot, PR2-plot, and neutrality analyses suggested that both mutation pressure and natural selection exert influence on the codon bias in these 13 Gnetales species, with natural selection emerging as the predominant influence. Correspondence analysis (COA) demonstrated variation in the codon usage patterns among the Gnetales species and indicated mutation pressure is another factor that could impact CUB. Additionally, our research identified a positive correlation between the measure of idiosyncratic codon usage level of conservatism (MILC) and synonymous codon usage order (SCUO) values, indicative of CUB’s potential influence on gene expression. The comparative analysis concerning codon usage frequencies among the 13 Gnetales species and 4 model organisms revealed that Saccharomyces cerevisiae and Nicotiana tabacum were the optimal exogenous expression hosts. Furthermore, the cluster and phylogenetic analyses illustrated distinct patterns of differentiation, implying that codons, even with weak or neutral preferences, could affect the evolutionary trajectories of these species. Our results reveal the characteristics of codon usage patterns and contribute to an enhanced comprehension of evolutionary mechanisms in Gnetales species.
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Duchev, Z., R. Petrova, B. Sirakovа, A. Kolev, and I. Sirakov. "Prion Protein Gene Frequencies in Three Native Sheep Breeds from Bulgaria." Acta Microbiologica Bulgarica 41, no. 1 (2025): 76–82. https://doi.org/10.59393/amb25410110.
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Scrapie in sheep is a fatal neurodegenerative infectious disease with a long incubation period (2–3 years). The disease has been present in Europe since the 18th century. The predisposition of sheep to scrapie is associated primarily with polymorphisms in the ovine prion protein (PrP) gene, PrnP, especially in the three codons 136, 154 and 171 for the classical form and in codon 141 for the atypical form. The PrnP genotypes of 57 healthy animals from three of the native Bulgarian breeds: Sofia Sheep, Breznik Sheep, and Western Balkan Mountains Sheep were determined. All analysed animals, except one, were Leucine-homozygous in codon 141, which indicates resistance to atypical scrapie. Codon 141 encoding Phenylalanine was observed in one animal, which has not been reported previously in other studies of local breeds in Bulgaria. Six al¬leles, including the rare AHR, were observed, the most frequent in all breeds being ARQ. Twelve genotypes of various frequencies were identified: - nine within the Sofia Sheep breed, five within the Breznik Sheep breed and six within Western Balkan Mountains Sheep breed. The most unfavourable VRQ/VRQ genotype was not found; however, ARR/ARR rams were also not found. Two genotypes of increased susceptibility to classical scrapie were identified for the first time in a Bulgarian breed: ARH/ARH (risk group 4) and ARH/ VRQ (risk group 5) in Sofia Sheep. The rich diversity findings in a small sample size in this study justify the need for further research on a larger scale of the autochthonous breeds in Bulgaria.
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Sheng, Jiajing, Xuan She, Xiaoyu Liu, Jia Wang, and Zhongli Hu. "Comparative analysis of codon usage patterns in chloroplast genomes of five Miscanthus species and related species." PeerJ 9 (September 23, 2021): e12173. http://dx.doi.org/10.7717/peerj.12173.
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Miscanthus is not only a perennial fiber biomass crop, but also valuable breeding resource for its low-nutrient requirements, photosynthetic efficiency and strong adaptability to environment. In the present study, the codon usage patterns of five different Miscanthus plants and other two related species were systematically analyzed. The results indicated that the cp genomes of the seven representative species were preference to A/T bases and A/T-ending codons. In addition, 21 common high-frequency codons and 4–11 optimal codons were detected in the seven chloroplast genomes. The results of ENc-plot, PR2-plot and neutrality analysis revealed the codon usage patterns of the seven chloroplast genomes are influenced by multiple factors, in which nature selection is the main influencing factor. Comparative analysis of the codon usage frequencies between the seven representative species and four model organisms suggested that Arabidopsis thaliana, Populus trichocarpa and Saccharomyces cerevisiae could be considered as preferential appropriate exogenous expression receptors. These results might not only provide important reference information for evolutionary analysis, but also shed light on the way to improve the expression efficiency of exogenous gene in transgenic research based on codon optimization.
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Kameda, Takeru, Katsura Asano, and Yuichi Togashi. "Free energy landscape of RNA binding dynamics in start codon recognition by eukaryotic ribosomal pre-initiation complex." PLOS Computational Biology 17, no. 6 (2021): e1009068. http://dx.doi.org/10.1371/journal.pcbi.1009068.
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Specific interaction between the start codon, 5’-AUG-3’, and the anticodon, 5’-CAU-3’, ensures accurate initiation of translation. Recent studies show that several near-cognate start codons (e.g. GUG and CUG) can play a role in initiating translation in eukaryotes. However, the mechanism allowing initiation through mismatched base-pairs at the ribosomal decoding site is still unclear at an atomic level. In this work, we propose an extended simulation-based method to evaluate free energy profiles, through computing the distance between each base-pair of the triplet interactions involved in recognition of start codons in eukaryotic translation pre-initiation complex. Our method provides not only the free energy penalty for mismatched start codons relative to the AUG start codon, but also the preferred pathways of transitions between bound and unbound states, which has not been described by previous studies. To verify the method, the binding dynamics of cognate (AUG) and near-cognate start codons (CUG and GUG) were simulated. Evaluated free energy profiles agree with experimentally observed changes in initiation frequencies from respective codons. This work proposes for the first time how a G:U mismatch at the first position of codon (GUG)-anticodon base-pairs destabilizes the accommodation in the initiating eukaryotic ribosome and how initiation at a CUG codon is nearly as strong as, or sometimes stronger than, that at a GUG codon. Our method is expected to be applied to study the affinity changes for various mismatched base-pairs.
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Hartl, D. L., E. N. Moriyama, and S. A. Sawyer. "Selection intensity for codon bias." Genetics 138, no. 1 (1994): 227–34. http://dx.doi.org/10.1093/genetics/138.1.227.
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Abstract The patterns of nonrandom usage of synonymous codons (codon bias) in enteric bacteria were analyzed. Poisson random field (PRF) theory was used to derive the expected distribution of frequencies of nucleotides differing from the ancestral state at aligned sites in a set of DNA sequences. This distribution was applied to synonymous nucleotide polymorphisms and amino acid polymorphisms in the gnd and putP genes of Escherichia coli. For the gnd gene, the average intensity of selection against disfavored synonymous codons was estimated as approximately 7.3 x 10(-9); this value is significantly smaller than the estimated selection intensity against selectively disfavored amino acids in observed polymorphisms (2.0 x 10(-8)), but it is approximately of the same order of magnitude. The selection coefficients for optimal synonymous codons estimated from PRF theory were consistent with independent estimates based on codon usage for threonine and glycine. Across 118 genes in E. coli and Salmonella typhimurium, the distribution of estimated selection coefficients, expressed as multiples of the effective population size, has a mean and standard deviation of 0.5 +/- 0.4. No significant differences were found in the degree of codon bias between conserved positions and replacement positions, suggesting that translational misincorporation is not an important selective constraint among synonymous polymorphic codons in enteric bacteria. However, across the first 100 codons of the genes, conserved amino acids with identical codons have significantly greater codon bias than that of either synonymous or nonidentical codons, suggesting that there are unique selective constraints, perhaps including mRNA secondary structures, in this part of the coding region.
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Song, Yuxuan, Meng Shen, Fuliang Cao, and Xiaoming Yang. "Compare Analysis of Codon Usage Bias of Nuclear Genome in Eight Sapindaceae Species." International Journal of Molecular Sciences 26, no. 1 (2024): 39. https://doi.org/10.3390/ijms26010039.
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Codon usage bias (CUB) refers to the different frequencies with which various codons are utilized within a genome. Examining CUB is essential for understanding genome structure, function, and evolution. However, little was known about codon usage patterns and the factors influencing the nuclear genomes of eight ecologically significant Sapindaceae species widely utilized for food and medicine. In this study, an analysis of nucleotide composition revealed a higher A/T content and showed a preference for A/T at the third codon position in the eight species of Sapindaceae. A correspondence analysis of relative synonymous codon usage explained only part of the variation, suggesting that not only natural selection but also various other factors contribute to selective constraints on codon bias in the nuclear genomes of the eight Sapindaceae species. Additionally, ENC-GC3 plot, PR2-Bias, and neutrality plot analyses indicated that natural selection exerted a greater influence than mutation pressure across these eight species. Among the eight Sapindaceae species, 16 to 26 optimal codons were identified, with two common high-frequency codons: AGA (encoding Arg) and GCU (encoding Ala). The clustering heat map, which included the 8 Sapindaceae species and 13 other species, revealed two distinct clusters corresponding to monocots and dicots. This finding suggested that CUB analysis was particularly effective in elucidating evolutionary relationships at the family level. Collectively, our results emphasized the distinct codon usage characteristics and unique evolutionary traits of the eight Sapindaceae species.
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Kanduc, Darja. "Human Codon Usage: The Genetic Basis of Pathogen Latency." Global Medical Genetics 08, no. 03 (2021): 109–15. http://dx.doi.org/10.1055/s-0041-1729753.
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AbstractInfectious diseases pose two main compelling issues. First, the identification of the molecular factors that allow chronic infections, that is, the often completely asymptomatic coexistence of infectious agents with the human host. Second, the definition of the mechanisms that allow the switch from pathogen dormancy to pathologic (re)activation. Furthering previous studies, the present study (1) analyzed the frequency of occurrence of synonymous codons in coding DNA, that is, codon usage, as a genetic tool that rules protein expression; (2) described how human codon usage can inhibit protein expression of infectious agents during latency, so that pathogen genes the codon usage of which does not conform to the human codon usage cannot be translated; and (3) framed human codon usage among the front-line instruments of the innate immunity against infections. In parallel, it was shown that, while genetics can account for the molecular basis of pathogen latency, the changes of the quantitative relationship between codon frequencies and isoaccepting tRNAs during cell proliferation offer a biochemical mechanism that explains the pathogen switching to (re)activation. Immunologically, this study warns that using codon optimization methodologies can (re)activate, potentiate, and immortalize otherwise quiescent, asymptomatic pathogens, thus leading to uncontrollable pandemics.
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Hsiao, Yi-Yuong, Chorng-Horng Lin, Jong-Kang Liu, Tit-Yee Wong, and Jimmy Kuo. "Analysis of Codon Usage Patterns in Toxic DinoflagellateAlexandrium tamarensethrough Expressed Sequence Tag Data." Comparative and Functional Genomics 2010 (2010): 1–9. http://dx.doi.org/10.1155/2010/138538.
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We have analyzed synonymous codon usage in the genome ofA. tamarenseCCMP 1598 for protein-coding sequences from 10865 expressed sequence tags (ESTs). We reconstructed a total of 4284 unigenes, including 74 ribosomal protein and 40 plastid-related genes, from ESTs using FrameDP, an open reading frame (ORF) prediction program. Correspondence analysis ofA. tamarensegenes based on codon usage showed that the GC content at the third base of synonymous codons (GC3s) was strongly correlated with the first axis (r=0.93withP<.001). On the other hand, the second axis discriminated between presumed highly and low expressed genes, with expression levels being confirmed by the analysis of EST frequencies (r=−0.89withP<.001). Our results suggest that mutational bias is the major factor in shaping codon usage inA. tamarensegenome, but other factors, namely, translational selection, hydropathy, and aromaticity, also appear to influence the selection of codon usage in this species.
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Bakli, Mahfoud, Raul Pascalau, and Laura Smuleac. "Rare Codon Analysis in Rickettsia Affecting Recombinant Protein Expression in Escherichia coli." Advanced Research in Life Sciences 4, no. 1 (2020): 30–35. http://dx.doi.org/10.2478/arls-2020-0015.
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Abstract Rickettsia species are important emerging pathogens causing rickettsial diseases, which are important cause death worldwide. The number of recombinant proteins used for diagnostic and therapeutic applications has increased dramatically, which is important in determination of protein function, structure and antigensity. Although E. coli is widely used expression system, the codon bias can hamper protein expression due to the presence of rare codons in gene sequence coding protein of interest. Using bioinformatics tools, rare codon analysis of rickettsial genes was performed and compared to not expressed proteins in both R. prowazekii and R. rickettsii. A negative correlation between frequencies of rare codons in Rickettsia and success of rickettsial protein expression was observed. This study suggested a useful tool to improve rickettsial recombinant protein expression in E. coli.
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Levin, David B., and Beatrixe Whittome. "Codon usage in nucleopolyhedroviruses." Journal of General Virology 81, no. 9 (2000): 2313–25. http://dx.doi.org/10.1099/0022-1317-81-9-2313.
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Phylogenetic analyses based on baculovirus polyhedrin nucleotide and amino acid sequences revealed two major nucleopolyhedrovirus (NPV) clades, designated Group I and Group II. Subsequent phylogenetic analyses have revealed three Group II subclades, designated A, B and C. Variations in amino acid frequencies determine the extent of dissimilarity for divergent but structurally and functionally conserved genes and therefore significantly influence the analysis of phylogenetic relationships. Hence, it is important to consider variations in amino acid codon usage. The Genome Hypothesis postulates that genes in any given genome use the same coding pattern with respect to synonymous codons and that genes in phylogenetically related species generally show the same pattern of codon usage. We have examined codon usage in six genes from six NPVs and found that: (1) there is significant variation in codon use by genes within the same virus genome; (2) there is significant variation in the codon usage of homologous genes encoded by different NPVs; (3) there is no correlation between the level of gene expression and codon bias in NPVs; (4) there is no correlation between gene length and codon bias in NPVs; and (5) that while codon use bias appears to be conserved between viruses that are closely related phylogenetically, the patterns of codon usage also appear to be a direct function of the GC-content of the virus-encoded genes.
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Jiang, Long, An Chun Cheng, Ming Shu Wang, De Kang Zhu, and Ren Yong Jia. "Analysis of Codon Usage in Herpesvirus Glycoprotein B (gB) Gene." Advanced Materials Research 343-344 (September 2011): 721–28. http://dx.doi.org/10.4028/www.scientific.net/amr.343-344.721.
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Due to the degeneracy of genetic code, most amino acids are coded by more than one codon (synonymous codons). The synonymous codons are not used at equal frequencies both within and between organisms. Of the total 33 herpesvirus gB genes, approximately 9.1% of the total gB genes had low codon bias (ENC<35), 72.7% of the gB genes had high ENC values (ENC>50), indicating that these gB genes had random codon usage in herpesviruses. There might be no direct correlation between the codon usage bias and the host, which indicates that the tRNA abundance of the host was not the main factor influencing the codon usage bias. A plot of ENC vs. GC3 indicates that mutational bias may be a more important factor than tRNA abundance in determining codon usage bias of herpesvirus gB genes. Pearson correlation coefficients between the ENC value and corresponding GC%, cumulative GC% in 2nd (GC2%) and 3rd codon position (GC3%) of each herpesvirus gB gene were -0.621 (p<0.01), -0.656 (p<0.01) and -0.712 (p<0.01), respectively, which implies that significant correlations existed between them. But no significant correlations existed between ENC and cumulative GC% in 1st codon position of each herpesviral gB gene. Furthermore, significant correlations also existed between GC% and GC3% of 33 herpesvirus gB genes (r=0.856, p<0.01). So it seems that, GC content, and particularly GC content at the 3rd base position, contributing greatly to the effective number of codons, indicating that the mutational bias dominates over translational selection. Further analysis on the relationship between gene length and ENC of 33 herpesvirus gB genes demonstrated that the two factors were not correlated. Significant correlations were found between the gene expression levels assessed by CAI value and ENC (r = -0.424, p<0.05) and GC3 values (r = 0.644, p<0.01).
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Wang, Zhanjun, Beibei Xu, Bao Li, et al. "Comparative analysis of codon usage patterns in chloroplast genomes of six Euphorbiaceae species." PeerJ 8 (January 6, 2020): e8251. http://dx.doi.org/10.7717/peerj.8251.
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Euphorbiaceae plants are important as suppliers of biodiesel. In the current study, the codon usage patterns and sources of variance in chloroplast genome sequences of six different Euphorbiaceae plant species have been systematically analyzed. Our results revealed that the chloroplast genomes of six Euphorbiaceae plant species were biased towards A/T bases and A/T-ending codons, followed by detection of 17 identical high-frequency codons including GCT, TGT, GAT, GAA, TTT, GGA, CAT, AAA, TTA, AAT, CCT, CAA, AGA, TCT, ACT, TAT and TAA. It was found that mutation pressure was a minor factor affecting the variation of codon usage, however, natural selection played a significant role. Comparative analysis of codon usage frequencies of six Euphorbiaceae plant species with four model organisms reflected that Arabidopsis thaliana, Populus trichocarpa, and Saccharomyces cerevisiae should be considered as suitable exogenous expression receptor systems for chloroplast genes of six Euphorbiaceae plant species. Furthermore, it is optimal to choose Saccharomyces cerevisiae as the exogenous expression receptor. The outcome of the present study might provide important reference information for further understanding the codon usage patterns of chloroplast genomes in other plant species.
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Mezei, Mihaly. "Use of the Codon Table to Quantify the Evolutionary Role of Random Mutations." Algorithms 14, no. 9 (2021): 270. http://dx.doi.org/10.3390/a14090270.
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The various biases affecting RNA mutations during evolution is the subject of intense research, leaving the extent of the role of random mutations undefined. To remedy this lacuna, using the codon table, the number of codons representing each amino acid was correlated with the amino acid frequencies in different branches of the evolutionary tree. The correlations were seen to increase as evolution progressed. Furthermore, the number of RNA mutations that resulted in a given amino acid mutation were found to be correlated with several widely used amino acid similarity tables (used in sequence alignments). These correlations were seen to increase when the observed codon usage was factored in.
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Arella, Davide, Maddalena Dilucca, and Andrea Giansanti. "Codon usage bias and environmental adaptation in microbial organisms." Molecular Genetics and Genomics 296, no. 3 (2021): 751–62. http://dx.doi.org/10.1007/s00438-021-01771-4.
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AbstractIn each genome, synonymous codons are used with different frequencies; this general phenomenon is known as codon usage bias. It has been previously recognised that codon usage bias could affect the cellular fitness and might be associated with the ecology of microbial organisms. In this exploratory study, we investigated the relationship between codon usage bias, lifestyles (thermophiles vs. mesophiles; pathogenic vs. non-pathogenic; halophilic vs. non-halophilic; aerobic vs. anaerobic and facultative) and habitats (aquatic, terrestrial, host-associated, specialised, multiple) of 615 microbial organisms (544 bacteria and 71 archaea). Principal component analysis revealed that species with given phenotypic traits and living in similar environmental conditions have similar codon preferences, as represented by the relative synonymous codon usage (RSCU) index, and similar spectra of tRNA availability, as gauged by the tRNA gene copy number (tGCN). Moreover, by measuring the average tRNA adaptation index (tAI) for each genome, an index that can be associated with translational efficiency, we observed that organisms able to live in multiple habitats, including facultative organisms, mesophiles and pathogenic bacteria, are characterised by a reduced translational efficiency, consistently with their need to adapt to different environments. Our results show that synonymous codon choices might be under strong translational selection, which modulates the choice of the codons to differently match tRNA availability, depending on the organism’s lifestyle needs. To our knowledge, this is the first large-scale study that examines the role of codon bias and translational efficiency in the adaptation of microbial organisms to the environment in which they live.
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Pandima Devi, K., B. Sivamaruthi, PV Kiruthiga, and S. Karutha Pandian. "Study of p53 codon 72 polymorphism and codon 249 mutations in Southern India in relation to age, alcohol drinking and smoking habits." Human & Experimental Toxicology 29, no. 6 (2009): 451–58. http://dx.doi.org/10.1177/0960327109354938.
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Germline polymorphisms of genes involved in different steps of tumorigenesis like p53, the tumor suppressor gene, are reported to determine the individual susceptibility to cancer. Lung cancer is one of the most common and lethal cancers and tobacco smoking remains its most important etiologic factors. The most frequently p53 mutated codons of lung cancer are 72 (exon 4) and 249 (exon 7). Since mutations in the p53 gene are present in ∼40% of all human lung cancers and are more common in smokers than in nonsmokers, we aimed to detect the status of p53 at codon 72 for Arg/Arg or Arg/Pro or Pro/Pro allele polymorphism and p53 codon 249 mutation in smokers and nonsmokers of South India. Allele frequencies in the nonsmokers were 0.16 for the Arg/Pro allele and 0.84 for the Pro/Pro allele in our study population. Among the smokers, the frequencies of the Arg/Pro, Arg/Arg, and Pro/Pro alleles were 0.88, 0.04, and 0.08, respectively. No mutation was detected in both smokers and nonsmokers in p53 codon 249. From the worldwide scenario, it can be speculated that the smokers, with Arg/Pro genotype are more prone for lung cancer or to other types of cancer.
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de Oliveira, Janaina Lima, Atahualpa Castillo Morales, Laurence D. Hurst, Araxi O. Urrutia, Christopher R. L. Thompson, and Jason B. Wolf. "Inferring Adaptive Codon Preference to Understand Sources of Selection Shaping Codon Usage Bias." Molecular Biology and Evolution 38, no. 8 (2021): 3247–66. http://dx.doi.org/10.1093/molbev/msab099.
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Abstract Alternative synonymous codons are often used at unequal frequencies. Classically, studies of such codon usage bias (CUB) attempted to separate the impact of neutral from selective forces by assuming that deviations from a predicted neutral equilibrium capture selection. However, GC-biased gene conversion (gBGC) can also cause deviation from a neutral null. Alternatively, selection has been inferred from CUB in highly expressed genes, but the accuracy of this approach has not been extensively tested, and gBGC can interfere with such extrapolations (e.g., if expression and gene conversion rates covary). It is therefore critical to examine deviations from a mutational null in a species with no gBGC. To achieve this goal, we implement such an analysis in the highly AT rich genome of Dictyostelium discoideum, where we find no evidence of gBGC. We infer neutral CUB under mutational equilibrium to quantify “adaptive codon preference,” a nontautologous genome wide quantitative measure of the relative selection strength driving CUB. We observe signatures of purifying selection consistent with selection favoring adaptive codon preference. Preferred codons are not GC rich, underscoring the independence from gBGC. Expression-associated “preference” largely matches adaptive codon preference but does not wholly capture the influence of selection shaping patterns across all genes, suggesting selective constraints associated specifically with high expression. We observe patterns consistent with effects on mRNA translation and stability shaping adaptive codon preference. Thus, our approach to quantifying adaptive codon preference provides a framework for inferring the sources of selection that shape CUB across different contexts within the genome.
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Imran, Mohd. "Substitution Trends in the Mitochondrial Cytochrome B Protein Coding Gene and the Corresponding Changes in its Amino Acid Sequence in Catfish Species." International Journal of Research in Science and Technology 12, no. 03 (2022): 11–18. http://dx.doi.org/10.37648/ijrst.v12i03.003.
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The study describes the divergence trends in the partial segment cytochrome b gene (cyt. b) in six catfish species on the basis of the nucleotide substitutions and their location in the triplet codons of the resulting amino acid sequence. The nucleotide sequences of all six species were found A+T rich with average nucleotide frequencies as A: 28.6%; T: 29.3%; G: 13.6%; C: 28.5%, showing an antiguanine bias which was found strongest in R. rita. The transition substitution rate was found highest at 3rd codon position in all the species. The evolutionary divergence follows the trend as highest at 3rd codon position followed by 1st codon position and the least on 2 nd codon position among all species. When amino acid sequences of cytochrome b were aligned, only 12 sites were found with a total 29 amino acid substitutions. which is a resultant of the substitution trend of three codon positions. Majority of the amino acid substitutions were found synonymous and conservative. Three different variability trends are observed in the cyt. b gene which run simultaneously on three different codon positions of triplet codons. Nucleotide substitutions at three codon positions follows the order 3 rd (87) >1st (32) >2nd (03) the frequency of amino acid substitution follows the order 1 st (11) >3rd (04) >2 nd (02); and the frequency of non-conservative amino acid changes found as 2 nd (1:2) >1st (5:11) >3rd (1:4). The study has provided an in-depth understanding of the relative variability and substitution trends in the mitochondrial cytochrome b gene in catfish species at both DNA and protein level.
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PIGANEAU, GWENAËL, ROLAND WESTRELIN, BERNARD TOURANCHEAU, and CHRISTIAN GAUTIER. "Multiplicative versus additive selection in relation to genome evolution: a simulation study." Genetical Research 78, no. 2 (2001): 171–75. http://dx.doi.org/10.1017/s0016672301005249.
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The evolution of molecular quantitative traits, such as codon usage bias or base frequencies, can be explained as the result of mutational biases alone, or as the result of mutation and selection. Whereas mutation models can be investigated easily, realistic modelling of selection-directed genome evolution is analytically intractable, and numerical calculations require substantial computer resources. We investigated the evolution of optimal codon frequency under additive and multiplicative effects of selected linked codons. We show that additive selective effects of many linked sites cannot be effective in genomes when the number of selected sites is greater than the effective population size, a realistic assumption according to current molecular data. We then discuss the implications of these results for isochore evolution in vertebrates.
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Sharp, Paul M., Laura R. Emery, and Kai Zeng. "Forces that influence the evolution of codon bias." Philosophical Transactions of the Royal Society B: Biological Sciences 365, no. 1544 (2010): 1203–12. http://dx.doi.org/10.1098/rstb.2009.0305.
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The frequencies of alternative synonymous codons vary both among species and among genes from the same genome. These patterns have been inferred to reflect the action of natural selection. Here we evaluate this in bacteria. While intragenomic variation in many species is consistent with selection favouring translationally optimal codons, much of the variation among species appears to be due to biased patterns of mutation. The strength of selection on codon usage can be estimated by two different approaches. First, the extent of bias in favour of translationally optimal codons in highly expressed genes, compared to that in genes where selection is weak, reveals the long-term effectiveness of selection. Here we show that the strength of selected codon usage bias is highly correlated with bacterial growth rate, suggesting that selection has favoured translational efficiency. Second, the pattern of bias towards optimal codons at polymorphic sites reveals the ongoing action of selection. Using this approach we obtained results that were completely consistent with the first method; importantly, the frequency spectra of optimal codons at polymorphic sites were similar to those predicted under an equilibrium model. Highly expressed genes in Escherichia coli appear to be under continuing strong selection, whereas selection is very weak in genes expressed at low levels.
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Miller, Justin B., Lauren M. McKinnon, Michael F. Whiting, and Perry G. Ridge. "CAM: an alignment-free method to recover phylogenies using codon aversion motifs." PeerJ 7 (June 4, 2019): e6984. http://dx.doi.org/10.7717/peerj.6984.
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Background Common phylogenomic approaches for recovering phylogenies are often time-consuming and require annotations for orthologous gene relationships that are not always available. In contrast, alignment-free phylogenomic approaches typically use structure and oligomer frequencies to calculate pairwise distances between species. We have developed an approach to quickly calculate distances between species based on codon aversion. Methods Utilizing a novel alignment-free character state, we present CAM, an alignment-free approach to recover phylogenies by comparing differences in codon aversion motifs (i.e., the set of unused codons within each gene) across all genes within a species. Synonymous codon usage is non-random and differs between organisms, between genes, and even within a single gene, and many genes do not use all possible codons. We report a comprehensive analysis of codon aversion within 229,742,339 genes from 23,428 species across all kingdoms of life, and we provide an alignment-free framework for its use in a phylogenetic construct. For each species, we first construct a set of codon aversion motifs spanning all genes within that species. We define the pairwise distance between two species, A and B, as one minus the number of shared codon aversion motifs divided by the total codon aversion motifs of the species, A or B, containing the fewest motifs. This approach allows us to calculate pairwise distances even when substantial differences in the number of genes or a high rate of divergence between species exists. Finally, we use neighbor-joining to recover phylogenies. Results Using the Open Tree of Life and NCBI Taxonomy Database as expected phylogenies, our approach compares well, recovering phylogenies that largely match expected trees and are comparable to trees recovered using maximum likelihood and other alignment-free approaches. Our technique is much faster than maximum likelihood and similar in accuracy to other alignment-free approaches. Therefore, we propose that codon aversion be considered a phylogenetically conserved character that may be used in future phylogenomic studies. Availability CAM, documentation, and test files are freely available on GitHub at https://github.com/ridgelab/cam.
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Bar-Eli, M., H. Ahuja, N. Gonzalez-Cadavid, A. Foti, and MJ Cline. "Analysis of N-RAS exon-1 mutations in myelodysplastic syndromes by polymerase chain reaction and direct sequencing." Blood 73, no. 1 (1989): 281–83. http://dx.doi.org/10.1182/blood.v73.1.281.bloodjournal731281.
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Mutations in codons 12 or 13 of the first exon of the N-RAS gene have been reported in myelodysplastic syndromes (MDS) in frequencies that vary between 9% and 40% depending on the techniques used in analysis. Gene amplification and direct sequencing provides the only unambiguous method of detecting those mutations that induce amino acid alterations. Using this technique, we analyzed 21 MDS patients for mutations in exon- 1 of N-RAS. Codon 12 mutations substituting aspartic acid (GAT) for glycine (GGT) were found in four cases, and a codon 13 mutation substituting alanine (GCT) for glycine (GGT) was detected in one patient. We conclude that N-RAS exon-1 mutations in one patient. We conclude that N-RAS exon-1 mutations producing amino acid changes occur in about 20% to 25% of MDS cases.
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Al-Allawi, Nasir A. S., Kawa M. A. Hassan, Anwar K. Sheikha, Farida F. Nerweiy, Raji S. Dawood, and Jaladet Jubrael. "-Thalassemia Mutations among Transfusion-Dependent Thalassemia Major Patients in Northern Iraq." Molecular Biology International 2010 (July 5, 2010): 1–4. http://dx.doi.org/10.4061/2010/479282.
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Molecular defects responsible for -thalassemias (thal) were investigated among 254 chromosomes from 127 transfusion-dependent unrelated thalassemic patients from two provinces in Northern Iraq. Among fourteen identified mutations, the seven most common found in 88.2% of the thal chromosomes were: IVS-II-1 (), IVS-I-1 (), codon 8 (), codon 39 (), codon 8/9 (), codon 44 (), and codon 5 (). There were some notable differences in frequencies of various mutations in comparison to other Eastern Mediterranean populations, as well as between the two provinces studied. The latter illustrates the relative heterogeneity of the mutations distribution in Iraq, and the need to screen other areas of the country, to ensure establishing an effective prenatal program.
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Cavic, Milena, Jelena Spasic, Ana Krivokuca, et al. "TP53 and DNA-repair gene polymorphisms genotyping as a low-cost lung adenocarcinoma screening tool." Journal of Clinical Pathology 72, no. 1 (2018): 75–80. http://dx.doi.org/10.1136/jclinpath-2018-205553.
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AimTP53 and DNA repair polymorphisms have been proposed as cancer risk factors. This study evaluated the usability of TP53 Arg72Pro single-nucleotide polymorphism, XRCC1 Arg399Gln and RAD51 G135C as a low-cost lung adenocarcinoma screening tool.Patients and methodsThis case–control study included 78 atients with lung adenocarcinoma and 79 healthy matched controls. TP53, XRCC1 and RAD51 genotyping was done by PCR followed by restriction length polymorphism. Descriptive analyses included genotype and allelic frequencies and deviations of the frequencies from those expected under Hardy-Weinberg equilibrium were assessed using the χ2 test. The OR and 95% CIs were calculated as an estimate of relative risk, with significance set at p value <0.05.ResultsThe TP53 codon 72 Pro allele and the XRCC1 codon 399 Arg allele in a homozygous state were associated with lung adenocarcinoma (p=0.037; OR (95% CI) 2.42 (1.10 to 5.31)), that is, p=0.037; OR (95% CI) 2.16 (1.08 to 4.33), respectively. Also, carriers of the TP53 codon 72 Pro allele and the XRCC1 codon 399 ArgArg genotype older than 50 showed an even higher risk of developing lung adenocarcinoma (p=0.03 in both cases).ConclusionsThe TP53 codon 72 Arg allele and XRCC1 codon 399 Gln allele are likely to have a protective effect against lung adenocarcinoma, especially in individuals older than 50 years of age. XRCC1 and TP53 genotyping might be a useful low-cost tool for evaluating individual lung cancer risk, leading to earlier detection and management of this disease.
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Bar-Eli, M., H. Ahuja, N. Gonzalez-Cadavid, A. Foti, and MJ Cline. "Analysis of N-RAS exon-1 mutations in myelodysplastic syndromes by polymerase chain reaction and direct sequencing." Blood 73, no. 1 (1989): 281–83. http://dx.doi.org/10.1182/blood.v73.1.281.281.
Full textAbstract:
Abstract Mutations in codons 12 or 13 of the first exon of the N-RAS gene have been reported in myelodysplastic syndromes (MDS) in frequencies that vary between 9% and 40% depending on the techniques used in analysis. Gene amplification and direct sequencing provides the only unambiguous method of detecting those mutations that induce amino acid alterations. Using this technique, we analyzed 21 MDS patients for mutations in exon- 1 of N-RAS. Codon 12 mutations substituting aspartic acid (GAT) for glycine (GGT) were found in four cases, and a codon 13 mutation substituting alanine (GCT) for glycine (GGT) was detected in one patient. We conclude that N-RAS exon-1 mutations in one patient. We conclude that N-RAS exon-1 mutations producing amino acid changes occur in about 20% to 25% of MDS cases.
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Rima, B. K., and N. V. McFerran. "Dinucleotide and stop codon frequencies in single-stranded RNA viruses." Journal of General Virology 78, no. 11 (1997): 2859–70. http://dx.doi.org/10.1099/0022-1317-78-11-2859.
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Keeler, Shamus P., Nicole L. Bernarsky, Jane E. Huffman, and Douglas E. Roscoe. "A Survey of the Prion Protein Gene Heterogeneity in New Jersey White-Tailed Deer (Odocoileus virginianus)." Journal of the Pennsylvania Academy of Science 85, no. 4 (2011): 183–87. http://dx.doi.org/10.5325/jpennacadscie.85.4.0183.
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Abstract Polymorphisms within the prion protein gene (Prnp) have been associated with modified susceptibility to chronic wasting disease (CWD) in white-tailed deer (Odocoileus virginianus). Studies of naturally infected white-tailed deer have determined that polymorphisms in the cervid Prnp at codons 95, 96, and 116 may provide reduced susceptibility or slowed progression of CWD. A survey was performed to determine the Prnp heterogeneity within New Jersey white-tailed deer. No CWD positive deer have been reported in New Jersey and all animals included in this study were determined to be CWD negative before the start of the project. The Prnp genes of 150 hunter-harvested deer were sequenced. All polymorphisms were identified and allelic frequencies were calculated. Seventy percent of the deer sampled in New Jersey were homozygous at codon 95 (glutamine) and codon 96 (glycine) and 94.7% had at least one copy of this allele. Only 2 % of the deer sampled had a single copy of the allele with histidine at Codon 95 and a glycine at Codon 96, which is under represented in naturally infected deer and may provide resistance to infection. These deer were found only in the southwestern portion of New Jersey. The genetic heterogeneity and distribution of the PrP gene of New Jersey white-tailed deer adds to our current understanding of the Prnp diversity within this species.
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Xiao, Guilian, Junzhi Zhou, Zhiheng Huo, et al. "The Shift in Synonymous Codon Usage Reveals Similar Genomic Variation during Domestication of Asian and African Rice." International Journal of Molecular Sciences 23, no. 21 (2022): 12860. http://dx.doi.org/10.3390/ijms232112860.
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The domestication of wild rice occurred together with genomic variation, including the synonymous nucleotide substitutions that result in synonymous codon usage bias (SCUB). SCUB mirrors the evolutionary specialization of plants, but its characteristics during domestication were not yet addressed. Here, we found cytosine- and guanidine-ending (NNC and NNG) synonymous codons (SCs) were more pronounced than adenosine- and thymine-ending SCs (NNA and NNT) in both wild and cultivated species of Asian and African rice. The ratios of NNC/G to NNA/T codons gradually decreased following the rise in the number of introns, and the preference for NNA/T codons became more obvious in genes with more introns in cultivated rice when compared with those in wild rice. SCUB frequencies were heterogeneous across the exons, with a higher preference for NNA/T in internal exons than in terminal exons. The preference for NNA/T in internal but not terminal exons was more predominant in cultivated rice than in wild rice, with the difference between wild and cultivated rice becoming more remarkable with the rise in exon numbers. The difference in the ratios of codon combinations representing DNA methylation-mediated conversion from cytosine to thymine between wild and cultivated rice coincided with their difference in SCUB frequencies, suggesting that SCUB reveals the possible association between genetic and epigenetic variation during the domestication of rice. Similar patterns of SCUB shift in Asian and African rice indicate that genomic variation occurs in the same non-random manner. SCUB representing non-neutral synonymous mutations can provide insight into the mechanism of genomic variation in domestication and can be used for the genetic dissection of agricultural traits in rice and other crops.
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Hodgman, Matthew W., Justin B. Miller, Taylor E. Meurs, and John S. K. Kauwe. "CUBAP: an interactive web portal for analyzing codon usage biases across populations." Nucleic Acids Research 48, no. 19 (2020): 11030–39. http://dx.doi.org/10.1093/nar/gkaa863.
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Abstract Synonymous codon usage significantly impacts translational and transcriptional efficiency, gene expression, the secondary structure of both mRNA and proteins, and has been implicated in various diseases. However, population-specific differences in codon usage biases remain largely unexplored. Here, we present a web server, https://cubap.byu.edu, to facilitate analyses of codon usage biases across populations (CUBAP). Using the 1000 Genomes Project, we calculated and visually depict population-specific differences in codon frequencies, codon aversion, identical codon pairing, co-tRNA codon pairing, ramp sequences, and nucleotide composition in 17,634 genes. We found that codon pairing significantly differs between populations in 35.8% of genes, allowing us to successfully predict the place of origin for African and East Asian individuals with 98.8% and 100% accuracy, respectively. We also used CUBAP to identify a significant bias toward decreased CTG pairing in the immunity related GTPase M (IRGM) gene in East Asian and African populations, which may contribute to the decreased association of rs10065172 with Crohn's disease in those populations. CUBAP facilitates in-depth gene-specific and codon-specific visualization that will aid in analyzing candidate genes identified in genome-wide association studies, identifying functional implications of synonymous variants, predicting population-specific impacts of synonymous variants and categorizing genetic biases unique to certain populations.
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Karlin, Samuel, Jan Mrázek, Allan Campbell, and Dale Kaiser. "Characterizations of Highly Expressed Genes of Four Fast-Growing Bacteria." Journal of Bacteriology 183, no. 17 (2001): 5025–40. http://dx.doi.org/10.1128/jb.183.17.5025-5040.2001.
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ABSTRACT Predicted highly expressed (PHX) genes are characterized for the completely sequenced genomes of the four fast-growing bacteriaEscherichia coli, Haemophilus influenzae, Vibrio cholerae, and Bacillus subtilis. Our approach to ascertaining gene expression levels relates to codon usage differences among certain gene classes: the collection of all genes (average gene), the ensemble of ribosomal protein genes, major translation/transcription processing factors, and genes for polypeptides of chaperone/degradation complexes. A gene is predicted highly expressed (PHX) if its codon frequencies are close to those of the ribosomal proteins, major translation/transcription processing factor, and chaperone/degradation standards but strongly deviant from the average gene codon frequencies. PHX genes identified by their codon usage frequencies among prokaryotic genomes commonly include those for ribosomal proteins, major transcription/translation processing factors (several occurring in multiple copies), and major chaperone/degradation proteins. Also PHX genes generally include those encoding enzymes of essential energy metabolism pathways of glycolysis, pyruvate oxidation, and respiration (aerobic and anaerobic), genes of fatty acid biosynthesis, and the principal genes of amino acid and nucleotide biosyntheses. Gene classes generally not PHX include most repair protein genes, virtually all vitamin biosynthesis genes, genes of two-component sensor systems, most regulatory genes, and most genes expressed in stationary phase or during starvation. Members of the set of PHX aminoacyl-tRNA synthetase genes contrast sharply between genomes. There are also subtle differences among the PHX energy metabolism genes between E. coli andB. subtilis, particularly with respect to genes of the tricarboxylic acid cycle. The good agreement of PHX genes of E. coli and B. subtiliswith high protein abundances, as assessed by two-dimensional gel determination, is verified. Relationships of PHX genes with stoichiometry, multifunctionality, and operon structures are also examined. The spatial distribution of PHX genes within each genome reveals clusters and significantly long regions without PHX genes.
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Barillet, F., D. Mariat, Y. Amigues, et al. "Identification of seven haplotypes of the caprine PrP gene at codons 127, 142, 154, 211, 222 and 240 in French Alpine and Saanen breeds and their association with classical scrapie." Journal of General Virology 90, no. 3 (2009): 769–76. http://dx.doi.org/10.1099/vir.0.006114-0.
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In sheep, susceptibility to scrapie is mainly influenced by polymorphisms of the PrP gene. In goats, there are to date few data related to scrapie susceptibility association with PrP gene polymorphisms. In this study, we first investigated PrP gene polymorphisms of the French Alpine and Saanen breeds. Based on PrP gene open reading frame sequencing of artificial insemination bucks (n=404), six encoding mutations were identified at codons 127, 142, 154, 211, 222 and 240. However, only seven haplotypes could be detected: four (GIH154RQS, GIRQ211QS, GIRRK222S and GIRRQP240) derived from the wild-type allele (G127I142R154R211Q222S240) by a single-codon mutation, and two (S127IRRQP240 and GM142RRQP240) by a double-codon mutation. A case–control study was then implemented in a highly affected Alpine and Saanen breed herd (90 cases/164 controls). Mutations at codon 142 (I/M), 154 (R/H), 211 (R/Q) and 222 (Q/K) were found to induce a significant degree of protection towards natural scrapie infection. Compared with the baseline homozygote wild-type genotype I142R154R211Q222/IRRQ goats, the odds of scrapie cases in IRQ211Q/IRRQ and IRRK222/IRRQ heterozygous animals were significantly lower [odds ratio (OR)=0.133, P<0.0001; and OR=0.048, P<0.0001, respectively]. The heterozygote M142RRQ/IRRQ genotype was only protective (OR=0.243, P=0.0186) in goats also PP240 homozygous at codon 240. However, mutated allele frequencies in French Alpine and Saanen breeds were low (0.5–18.5 %), which prevent us from assessing the influence of all the possible genotypes in natural exposure conditions.
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FADIEL, A., S. LITHWICK, G. GANJI, and I. F. M. MARAI. "Structural and functional relationships shown by genomic analysis of Capra hircus genes." Journal of Agricultural Science 140, no. 2 (2003): 235–44. http://dx.doi.org/10.1017/s0021859602002903.
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The effect of base composition biases on codon usage patterns was investigated in the goat species Capra hircus, using custom-designed computational tools available within the public domain. Nucleotide frequencies were nearly equal and a slight increase of adenine–thymine (AT) over guanine–cytosine (GC) was detected throughout the dataset. However, this increase showed no influence on the bases at the third codon position (N3). C3 and G3 were found more often than A/T3, suggesting that there was a small or almost no influence of the general base composition on the N3 base composition. To understand more and analyse in-depth influence and interactions between base compositions and codons, further relative synonymous codon usage (RSCU) was investigated. Amino acid usage and the correlation between its usages were also investigated, using both basic sequence analysis and statistical analysis means (measures of correlation). These analyses were utilized to probe whether there were correlations between genes, genomic characteristics and their function. Genes with high GC and those with low GC were also investigated to see to what extent how a gene functions could influence its sequence structure and impose certain structural modifications. This investigation may shed light on many genomic features of Capra hircus genes and would be of significance for future biotechnology/research projects considering Capra for transgenic and advanced genomic initiatives.
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Amoli, Mahsa M., Bagher Larijani, Wendy Thomson, William E. R. Ollier, and Miguel A. Gonzalez-Gay. "Two Polymorphisms in the Epithelial Cell-Derived Neutrophil-Activating Peptide (ENA-78) Gene." Disease Markers 21, no. 2 (2005): 75–77. http://dx.doi.org/10.1155/2005/864525.
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Increased expression of epithelial cell-derived neutrophil-activating peptide (ENA-78) has been reported in several immune and inflammatory conditions suggesting its role in inflammatory response. We have identified two single nucleotide polymorphisms in the promoter and exon 2 of the ENA-78 gene by scanning the full length gene using DHPLC DNA fragment analysis and DNA sequencing.The polymorphism at position +398 (A/G from the first ATG codon) in exon 2 results in a synonymous substitution not resulting in an amino acid change. The promoter polymorphism was found at position −156 (C/G from the first ATG codon). An assay was designed for the detection of the polymorphisms using SNapshot ddNTP primer extension, followed by capillary electrophoresis (ABI 3100).Allele and genotype frequencies for the promoter −156 polymorphism are presented for 107 healthy Spanish and 54 UK Caucasians. Frequencies for the exon 2 polymorphism are also presented for 63 UK Caucasians.
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Perucchini, Matteo, Karen Griffin, Michael W. Miller, and Wilfred Goldmann. "PrP genotypes of free-ranging wapiti (Cervus elaphus nelsoni) with chronic wasting disease." Journal of General Virology 89, no. 5 (2008): 1324–28. http://dx.doi.org/10.1099/vir.0.83424-0.
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Variation in PrP prion gene sequence appears to modulate susceptibility to chronic wasting disease (CWD), a naturally occurring prion disease affecting four North American species of the family Cervidae. Wapiti (Cervus elaphus nelsoni) PrP is polymorphic at codon 132 [methionine (M) or leucine (L)]. We genotyped 171 samples, collected between 2002 and 2005 from CWD-infected and uninfected wapiti from three free-ranging populations in Colorado, USA, to study influences of PrP polymorphisms on CWD susceptibility further. Overall genotype frequencies for 124 apparently uninfected animals were 65.3 % MM132, 32.3 % ML132 and 2.4 % LL132; for 47 CWD-infected animals, these frequencies were 70.2 % MM132, 27.7 % ML132 and 2.1 % LL132. Surprisingly, our data revealed that, among recent (approx. 2002–2005) CWD cases detected in free-ranging Colorado wapiti, the three PrP codon 132 genotypes were represented in proportion to their abundance in sampled populations (P≥0.24) and all three genotypes showed equivalent susceptibility to infection.
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Pozzi, G., M. Meloni, E. Iona, et al. "rpoB Mutations in Multidrug-Resistant Strains of Mycobacterium tuberculosis Isolated in Italy." Journal of Clinical Microbiology 37, no. 4 (1999): 1197–99. http://dx.doi.org/10.1128/jcm.37.4.1197-1199.1999.
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Mutations of rpoB associated with rifampin resistance were studied in 37 multidrug-resistant (MDR) clinical strains ofMycobacterium tuberculosis isolated in Italy. At least one mutated codon was found in each MDR strain. It was always a single-base substitution leading to an amino acid change. Nine differentrpoB alleles, three of which had not been reported before, were found. The relative frequencies of specific mutations in this sample were different from those previously reported from different geographical areas, since 22 strains (59.5%) carried the mutated codon TTG in position 531 (Ser→Leu) and 11 (29.7%) had GAC in position 526 (His→Asp).
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Valentin, Mev Dominguez, Renata Canalle, Rosane de Paula Queiroz, and Luiz Gonzaga Tone. "Frequency of polymorphisms and protein expression of cyclin-dependent kinase inhibitor 1A (CDKN1A) in central nervous system tumors." Sao Paulo Medical Journal 127, no. 5 (2009): 288–94. http://dx.doi.org/10.1590/s1516-31802009000500008.
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CONTEXT AND OBJECTIVE: Genetic investigation of central nervous system (CNS) tumors provides valuable information about the genes regulating proliferation, differentiation, angiogenesis, migration and apoptosis in the CNS. The aim of our study was to determine the prevalence of genetic polymorphisms (codon 31 and 3' untranslated region, 3'UTR) and protein expression of the cyclin-dependent kinase inhibitor 1A (CDKN1A) gene in patients with and without CNS tumors. DESIGN AND SETTING: Analytical cross-sectional study with a control group, at the Molecular Biology Laboratory, Pediatric Oncology Department, Hospital das Clínicas de Ribeirão Preto. METHODS: 41 patients with CNS tumors and a control group of 161 subjects without cancer and paires for sex, age and ethnicity were genotyped using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Protein analysis was performed on 36 patients with CNS tumors, using the Western Blotting technique. RESULTS: The frequencies of the heterozygote (Ser/Arg) and polymorphic homozygote (Arg/Arg) genotypes of codon 31 in the control subjects were 28.0% and 1.2%, respectively. However, the 3'UTR site presented frequencies of 24.2% (C/T) and 0.6% (T/T). These frequencies were not statistically different (P > 0.05) from those seen in the patients with CNS tumors (19.4% and 0.0%, codon 31; 15.8% and 2.6%, 3'UTR site). Regarding the protein expression in ependymomas, 66.67% did not express the protein CDKN1A. The results for medulloblastomas and astrocytomas were similar: neither of them expressed the protein (57.14% and 61.54%, respectively). CONCLUSION: No significant differences in protein expression patterns or polymorphisms of CDKN1A in relation to the three types of CNS tumors were observed among Brazilian subjects.
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Cope, Alexander L., and Premal Shah. "Intragenomic variation in non-adaptive nucleotide biases causes underestimation of selection on synonymous codon usage." PLOS Genetics 18, no. 6 (2022): e1010256. http://dx.doi.org/10.1371/journal.pgen.1010256.
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Patterns of non-uniform usage of synonymous codons vary across genes in an organism and between species across all domains of life. This codon usage bias (CUB) is due to a combination of non-adaptive (e.g. mutation biases) and adaptive (e.g. natural selection for translation efficiency/accuracy) evolutionary forces. Most models quantify the effects of mutation bias and selection on CUB assuming uniform mutational and other non-adaptive forces across the genome. However, non-adaptive nucleotide biases can vary within a genome due to processes such as biased gene conversion (BGC), potentially obfuscating signals of selection on codon usage. Moreover, genome-wide estimates of non-adaptive nucleotide biases are lacking for non-model organisms. We combine an unsupervised learning method with a population genetics model of synonymous coding sequence evolution to assess the impact of intragenomic variation in non-adaptive nucleotide bias on quantification of natural selection on synonymous codon usage across 49 Saccharomycotina yeasts. We find that in the absence of a priori information, unsupervised learning can be used to identify genes evolving under different non-adaptive nucleotide biases. We find that the impact of intragenomic variation in non-adaptive nucleotide bias varies widely, even among closely-related species. We show that the overall strength and direction of translational selection can be underestimated by failing to account for intragenomic variation in non-adaptive nucleotide biases. Interestingly, genes falling into clusters identified by machine learning are also physically clustered across chromosomes. Our results indicate the need for more nuanced models of sequence evolution that systematically incorporate the effects of variable non-adaptive nucleotide biases on codon frequencies.
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Borodovsky, M. Yu, and S. M. Gusein-Zade. "A General Rule for Ranged Series of Codon Frequencies in Different Genomes." Journal of Biomolecular Structure and Dynamics 6, no. 5 (1989): 1001–12. http://dx.doi.org/10.1080/07391102.1989.10506527.
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