DNA Codons Research Articles

In Silico Optimization of DNA Codons in Genes Encoded by Various Variants of Ebola Virus

Ebola hemorrhagic fever (HF) is a serious and often deadly illness that infects primates, especially humans. Ebola virus disease (EVD) is very deadly and has no widespread treatment, making it one of the most lethal zoonotic infections. The viral genome is approximately 19 kb in length, non-segmented, linear, and negative single-stranded (-SS) RNA. The Ebola virus (EBOV) genome contains seven genes: GP, NP, L, and VP (VP30, VP24, VP35, VP40), which encode glycoprotein, nucleoprotein, RNA polymerase, and viral proteins. When we modified the DNA sequence by codon adaptation, we noted considerable increases in the codon adaptation index (CAI) and GC content when compared with that of the natural-type strain. On average, the NP gene in the modified DNA exhibited a 3.14-fold increase (equivalent to 213.5%) in CAI and a 1.2-fold increase (19.17%) in GC content. Similarly, the GP gene showed a 3.57-fold increase (257.14%) in CAI and a 1.16-fold increase (16.56%) in GC content. Furthermore, the modified DNA resulted in a 3.44-fold increase (244.8%) in CAI and a 1.22-fold increase (22.5%) in GC content for the VP35 gene, a 4.34-fold increase (334.8%) in CAI and a 1.26-fold increase (26.04%) in GC content for the VP30 gene, and a 3.84-fold increase (284.6%) in CAI and a 1.2-fold increase (21.2%) in GC content for the VP40 gene. The VP24 gene exhibited a 3.84-fold increase (284.61%) in CAI and a 1.23-fold increase (23.3%) in GC content, while the L gene showed a 3.84-fold increase (284.61%) in CAI and a 1.23-fold increase (23%) in GC content. The results obtained illustrate that modified genes can boost expression in a host organism without producing truncated proteins. Furthermore, GP or NP are considered as promising candidates for an EBOV vaccine, as they possess immunogenic properties and can stimulate an immune response.

Cancer cells possess different isotopic enrichment: Isotopic induced functionalizations of normal DNA mutations leading to cancer

Although the dynamics of telomeres during the life expectancy of normal cells has been extensively studied, there are still some unresolved issues regarding this research field. For example, the conditions required for telomere shortening leading to malignant transformations are not fully understood. In this work, we mass analyzed DNA of normal and cancer cells for comparing telomere isotopic compositions of white blood cells and cancer cells. We have found that the 1327 Da and 1672 Da characteristic telomere mass to charges cause differential mass distributions of about 1 Da among normal cells relative to cancer cells. These isotopic differences are consistent with a prior theory according to which replacing primordial, common isotopes of 1H, 12C, 14N, 16O, 24Mg, 31P and/or 32S by nonprimordial, uncommon isotopes of 2D, 13C, 15N, 17O, 25Mg and/or 33S leads to altered enzymatic dynamics. This replacement may subsequently modulate DNA and telomere codons resulting in transformation of normal cells to cancer cells (in 15 N depletion in telomeres dependent manner). The prior theory and the current data are consistent also with a recently observed non-uniform methylation pattern of the DNA of cancer cells relative to a more uniform methylation in the DNA of normal cells. We observe further evidence of nonprimordial isotopic accelerations of acetylations, methylations, hydroxylations and aminations of nucleosides with alterations of phosphorylations of nucleotides; which may explain the induction of mutations at the DNA, RNA and proteins leading to cancer and more general alterations of DNA, which are associated with aging. This difference in mass spectra between normal and cancer DNA may stem from different functionalizations and isotopic enrichments affecting the motion derived from nuclear magnetic moments (NMMs). We suggest that this phenomenon may lead to malignant transformation.

Unifying colors by primes

RGB and CYMK are two major coloring schemes currently available for light colors and pigment colors, respectively. Both systems use letter-based color codes that require a large range of values to represent different colors. The problem is that these two systems are hard to use for manipulating any operations involving combinations of colors, and they lack the capacity for inter-changeability or unification. Based on prime number theory and Goldbach’s conjecture, this study presents a universal color system (C235) using a number-based structure to encode, compute and unify all colors on a color wheel. The proposed C235 system offers a unified representation for the efficient encoding and effective manipulation of color. It can be applied to designing a high-rate LCD system and colorizing objects with multiple attributes and DNA codons, opening the door to manipulating colors and lights for even broader applications.

Bit Incorporated Codon Positional Encoder (BICPE) Algorithm for Privacy Preservation in Vertically Partitioned Data in Cloud

HIGHLIGHTS Fake transactions are inserted into database to hide item frequency. The input binary bits are grouped into N sets with length as four for encryption. Each item in a data set is encoded with A,C,G,T DNA codons. Encrypted Association rules are built for frequent items in a transaction.

Cyclic DNA codes over the ring $\mathbb{Z}_4+u\mathbb{Z}_4+u^2\mathbb{Z}_4$

In this work, we have investigated the one generator cyclic DNA codes with reverse and reverse complement constraints over the ring $R=\mathbb{Z}_4+u\mathbb{Z}_4+u^2\mathbb{Z}_4$ with $u^3=0$. Skew cyclic codes with reverse complement constraint are constructed over $R$. We have also determined a one-to-one correspondence between the elements of the ring $R$ and DNA codons satisfying the Watson-Crick complement. Finally, we have established some examples which satisfy the given constraints.

DNA Codon Recognition by a Cubane Wire: In Silico Approach

DNA codons, consisting of triplet nucleotides (NTs), could play important roles for RNA transcription and protein translation in living systems. Therefore, their recognition could be seen important for diagnosis and therapy purposes. Based on triplet sequence formations of Adenine (A), Guanine (G), Cytosine (C) and Thymine (T) NTs, 64 codons were investigated in this work regarding their complexation with a molecular cubane (CUB) wire. To achieve this aim, each of singular 64 codons and CUB were optimized to be prepared for docking processes of complex formations. Hence, 64 complexes of codon-CUB were docked to see the recognition potency of CUB wire versus each of DNA codons. Interestingly, the obtained docking scores indicated that the CUB could work specifically versus the DNA codons, in which G-rich and A-rich triples were seen to be more favorable for complexation with CUB in comparison with other C-rich and T-rich triplet codons. Moreover, the results indicated that not pure G triplet but GAG codon was the most favorable one to be recognized by the CUB wire. However, pure T triplet was the worst one for such complex formations. The results of this work remarkably indicated that the CUB wire could work for recognition process of DNA codons from each other and such recognition could be very much specified for each of G-rich and A-rich codons, in which GAG codon was the best one among all the 64 investigated codons.

New DNA Codes from Cyclic Codes over Mixed Alphabets

Let R=F4+uF4,withu2=u and S=F4+uF4+vF4,withu2=u,v2=v,uv=vu=0. In this paper, we study F4RS-cyclic codes of block length (α,β,γ) and construct cyclic DNA codes from them. F4RS-cyclic codes can be viewed as S[x]-submodules of Fq[x]⟨xα−1⟩×R[x]⟨xβ−1⟩×S[x]⟨xγ−1⟩. We discuss their generator polynomials as well as the structure of separable codes. Using the structure of separable codes, we study cyclic DNA codes. By using Gray maps ψ1 from R to F42 and ψ2 from S to F43, we give a one-to-one correspondence between DNA codons of the alphabets {A,T,G,C}2,{A,T,G,C}3 and the elements of R,S, respectively. Then we discuss necessary and sufficient conditions of cyclic codes over F4, R, S and F4RS to be reversible and reverse-complement. As applications, we provide examples of new cyclic DNA codes constructed by our results.

DNA Codes Over the Ring F₄[U]/〈U³〉

In this paper, we develop the method for constructing DNA codes of odd length over the finite chain ring $R=\mathbb {F}_{4}[u]/\langle u^{3}\rangle $ , which plays an important role in genetics, bioengineering and DNA computing. By using a Gray map $\eta $ from $R$ to $\mathbb {F}_{4}$ , we give a one-to-one correspondence between 64 DNA codons of the alphabet $\{A, T, G,C\}^{3}$ and the 64 elements of the chain ring $R$ . We also establish a map $\Theta $ from $R^{n}$ to $\{A, T, G,C\}^{3n}$ . Then we provide a necessary and sufficient condition for cyclic codes of odd length over the chain ring $R$ to be reversible. Finally, when $C$ is a reversible cyclic code over $R$ , we derive a necessary and sufficient condition for $\Theta (C)$ to be a DNA code.

Cloning and expression of in silico modeled protein enriched with branched chain amino acids in Pichia pastoris

We have earlier in silico designed the 3-dimensional structure of a protein enriched with branched chain amino acids (BCAA, 56.4%), having only α-helical coiled-coil structure. Here, homology modeling was used to improve the in silico designed protein model. The secondary and tertiary structures of improved protein model were predicted, and validated using various online bioinformatics tools. The amino acid sequence of the final predicted Protein Model-51 was EQLTKLEIVIRVLKLLKLIGGLVSLVEWVLTALVTLLGDKVLDDILTDVIMLVKKIL DKVIGIVYVLAILALILSEVLDILWLLEKLVEILEGHHHHHH. The amino acid sequence of the protein model was reverse translated to DNA sequence and codons were optimized using codon optimization tool. The chemically synthesized BCAA51 gene was cloned to pPICZαC vector, and transformed into DH5α E. coli strain. After successful transformation, the protein was expressed in P. pastoris system by inducing with 0.5% methanol, every 24 h for up to 144 h. The expressed protein was purified by His Select Nickel affinity chromatography with an yield of 1.412 mg/L. The recombinant protein was confirmed by SDS-PAGE and western blot analysis, which showed a clear band at the expected molecular weight of ~11 kDa. Thus, here we have shown that the in silico designed protein is successfully cloned and expressed in P. pastoris.

A quantum mechanical approach towards the calculation of transition probabilities between DNA codons

The role of quantum tunneling in altering the structure of nucleotides to each other and causing a mutational event in DNA has been a topic of debate for years. Here, we introduce a new quantum mechanical approach for analyzing a typical point-mutation in DNA strands. Assuming each codon as a base state, a superposition of codon states could provide a physical description for a set of codons encoding the same amino acid and there are transition amplitudes between them. We choose the amino acids Phe and Ile as our understudy bio-systems which are encoded by two and three codons, respectively. We treat them as large quantum systems and use double- and triple-well potential models to study the fundamental behaviors of them in interaction with a harmonic environment. We use the perturbation theory to calculate the transition probabilities between the codons which encoding the same amino acid and determine the transition rates of some point mutations. Moreover, we evaluate the quantum biological channel capacity for these transitions to show that the channel capacity depends on the system–environment interaction via the dissipation factor Γ. The obtained results demonstrate that the tunneling rate is under the control of capacity of the corresponding biological channel. In other words, the reduction in quantum channel capacity prevents the quantum tunneling rate to be increased.

Conservation of k-mer Composition and Correlation Contribution between Introns and Intergenic Regions of Animalia Genomes.

In this study, we pairwise-compared multiple genome regions, including genes, exons, coding DNA sequences (CDS), introns, and intergenic regions of 39 Animalia genomes, including Deuterostomia (27 species) and Protostomia (12 species), by applying established k-mer-based (alignment-free) comparison methods. We found strong correlations between the sequence structure of introns and intergenic regions, individual organisms, and within wider phylogenetical ranges, indicating the conservation of certain structures over the full range of analyzed organisms. We analyzed these sequence structures by quantifying the contribution of different sets of DNA words to the average correlation value by decomposing the correlation coefficients with respect to these word sets. We found that the conserved structures within introns, intergenic regions, and between the two were mainly a result of conserved tandem repeats with repeat units ≤ 2 bp (e.g., (AT)n), while other conserved sequence structures, such as those found between exons and CDS, were dominated by tandem repeats with repeat unit sizes of 3 bp in length and more complex DNA word patterns. We conclude that the conservation between intron and intergenic regions indicates a shared function of these sequence structures. Also, the similar differences in conserved structures with known origin, especially to the conservation between exons and CDS resulting from DNA codons, indicate that k-mer composition-based functional properties of introns and intergenic regions may differ from those of exons and CDS.

An Enhanced Bilateral Information Security towards a Conventional Cryptographic System using DNA Sequences

Objective: Information security is one of the essential futures challenged in data transmission through wireless networks. Networks are extremely exposed to security attacks and consign a great challenge today. Methods: In this paper we propose a new DNA Symmetric Cryptographic technique that employs Mathematical formula for encryption and decryption and private key is generated from blood analysis report. After Encryption DNA codons are generated as a cipher text which is decrypted through decryption algorithm into readable text. In this method we use classical cryptographic technique of substitution method in DNA Cryptography. Findings: The algorithm is implemented in Java Platform and comparison was prepared for encryption and decryption time for different file formats. Also size of encrypted file is also compared for different files. Improvement: DNA based approach which is more immune to cryptographic attacks. DNA Cryptography is a new and potentially excellent area that enhances data security. It helps to transmit highly confidential data efficiently and securely.

Codon-optimized human sodium iodide symporter (opt-hNIS) as a sensitive reporter and efficient therapeutic gene.

To generate a more efficient in vivo reporter and therapeutic gene, we optimized the coding sequence of the human sodium/iodide symporter (NIS) gene by replacing NIS DNA codons from wild type to new codons having the highest usage in human gene translation. The Codon Adaptation Index (CAI), representing the number of codons effective for human expression, was much improved (0.79 for hNIS, 0.97 for opt-hNIS). Both wild-type (hNIS) and optimized human NIS (opt-hNIS) were cloned into pcDNA3.1 and pMSCV vectors for transfection. Various cancer cell lines such as thyroid (TPC-1, FRO, B-CPAP), breast (MDA-MB-231), liver (Hep3B), cervical (HeLa), and glioma (U87MG) were transfected with pcDNA3.1/hNIS or pcDNA3.1/opt-hNIS. 125I uptake by opt-hNIS-expressing cells was 1.6 ~ 2.1 times higher than uptake by wild-type hNIS-expressing cells. Stable cell lines were also established by retroviral transduction using pMSCV/hNIS or pMSCV/opt-hNIS, revealing higher NIS protein levels and 125I uptake in opt-hNIS-expressing cells than in hNIS-expressing cells. Moreover, scintigraphic images from cell plates and mouse xenografts showed stronger signals from opt-hNIS-expressing cells than hNIS-expressing cells, and radioactivity uptake by opt-hNIS-expressing tumors was 2.3-fold greater than that by hNIS-expressing tumors. To test the efficacy of radioiodine therapy, mouse xenograft models were established with cancer cells expressing hNIS or opt-hNIS. 131I treatment reduced tumor sizes of hNIS- and opt-hNIS-expressing tumors to 0.57- and 0.27- fold, respectively, compared to their sizes before therapy, suggesting an improved therapeutic effect of opt-hNIS. In summary, this study shows that codon optimization strongly increases hNIS protein levels and radioiodine uptake, thus supporting opt-hNIS as a more sensitive reporter and efficient therapeutic gene.

On Symmetries and the Language of Information

Many writings on information mix information on a given system (IS), measurable information content of a given system (IM), and the (also measurable) information content that we communicate among us on a given system (IC). They belong to different levels and different aspects of information. The first (IS) involves everything that one possibly can, at least potentially, know about a system, but will never learn completely. The second (IM) contains quantitative data that one really learns about a system. The third (IC) relates rather to the language (including mathematical) by which we transmit information on the system to one another, rather than to the system itself. The information content of a system (IM —this is what we generally mean by information) may include all (relevant) data on each element of the system. However, we can reduce the quantity of information we need to mediate to each other (IC), if we refer to certain symmetry principles or natural laws which the elements of the given system correspond to. Instead of listing the data for all elements separately, even in a not very extreme case, we can give a short mathematical formula that informs about the data of the individual elements of the system. This abbreviated form of information delivery includes several conventions. These conventions are protocols that we have learnt before, and do not need to be repeated each time in the given community. These conventions include the knowledge that the scientific community accumulated earlier when discovered and formulated the symmetry principle or the law of nature, the language in which those regularities were discovered and formulated, for example, the symmetry principle or the law of nature, the language in which those regularities were formulated and then accepted by the community, and the mathematical marks and abbreviations that are known only for the members of the given scientific community. We do not need to repeat the rules of the convention each time, because the conveyed information includes them, and it is there in our minds behind our communicated data on the information content. I demonstrate this by using two examples, Kepler’s laws, and the law of correspondence between the DNA codons’ triplet structure and the individual amino acids which they encode. The information content of the language by which we communicate the obtained information cannot be identified with the information content of the system that we want to characterize, and moreover, it does not include all the possible information that we could potentially learn about the system. Symmetry principles and natural laws may reduce the information we need to communicate about a system, but we must keep in mind the conventions that we have learnt about the abbreviating mechanism of those principles, laws, and mathematical descriptions.

Quantification of Peptide Bond Types in Human Proteome Indicates How DNA Codons were Assembled at Prebiotic Conditions

[GADV]-protein world hypothesis [1] leaded me to quantification of decapeptides assembled from G, A, V, D in human proteome. The G, A, V, and D amino acids were related to the nucleotides Guanine (g), Cystosine (c), Uracil (u), and Adenine (a). The search revealed agreement with the genetic code. The types of prebiotic peptide bonds represent probably the first selection power that established the base order in the codons. The genetic code underwent three phases of formation, which explain why modern codons have their particular order of nucleotides: the monobase, dibase and the modern phase (tribase). Sequence alignments and 3D structures of aminoacyl-tRNA synthetases confirm the depicted picture of “relatedness” and the picture indicates how “relatedness” is used by aminoacyl-tRNA synthetases for navigation into and within of the C-terminal anticodon-binding domain. The findings presented here illustrate the novel concept of possible translation of the amino acid sequence into a nucleotide sequence that can be in interactive or contrary mode regarding to desired protein-RNA interactions. Hopefully, it could be used in synthetic biology.

Vibrational Characteristics of Genetic Codons: 5$'$-GGX-3$'$ and 5$'$-XGG-3$'$ (${\rm X} = {\rm A}, {\rm C}$, and T)

A theoretical study of the vibrational characteristics of six DNA codons (i.e., at the sequence forms 5' -GGX-3' and 5' -XGG-3'; X = A, C, and T) in gas phase is presented. The simulation results show that the spectra of the codons in the near infrared regime can be classified into five semi-distinct spectral sub-regimes, namely: two end regions and one region that separates the two sequence identifier regions with features that arise primarily from coupling between the GG bases and other bases (T, C, and A). This study reveals a number of phenomenological trends that have scientific relevance to spectroscopic characterization of DNA molecules. For example, spectra in the high-frequency end-regions arise primarily from vibrational modes associated with the O-H bonds at the 5 ' end or 3 ' end of the codons and the spectra in the low-frequency end-regions are formed primarily by the vibrational modes of the backbone. Conversely, in the lower-frequency side, the sequence-identifier region is composed of the C-H bond stretch vibrations in the planes of the corresponding DNA bases, and in the higher-frequency side, sequence-identifier region is composed of the N-H bond stretch vibrations in the planes of the corresponding DNA bases. In addition, the sequence-identifier dividing region almost exclusively contains vibrational modes due to coupling between the G nucleotides and other bases. As will be shown, all the vibrational modes in sequence identifier regions are localized at the corresponding DNA bases and exhibit a definable dependence on the sequence form of the codons under study.

Discovery and Investigation of Misincorporation of Serine at Asparagine Positions in Recombinant Proteins Expressed in Chinese Hamster Ovary Cells

Misincorporation of amino acids in proteins expressed in Escherichia coli has been well documented but not in proteins expressed in mammalian cells under normal recombinant protein production conditions. Here we report for the first time that Ser can be incorporated at Asn positions in proteins expressed in Chinese hamster ovary cells. This misincorporation was discovered as a result of intact mass measurement, peptide mapping analysis, and tandem mass spectroscopy sequencing. Our analyses showed that the substitution was not related to specific protein molecules or DNA codons and was not site-specific. We believe that the incorporation of Ser at sites coded for Asn was due to mischarging of tRNA(Asn) rather than to codon misreading. The rationale for substitution of Asn by Ser and not by other amino acids is also discussed. Further investigation indicated that the substitution was due to the starvation for Asn in the cell culture medium and that the substitution could be limited by using the Asn-rich feed. These observations demonstrate that the quality of expressed proteins should be closely monitored when altering cell culture conditions.

Comparison of equations describing the ranked frequency distributions of graphemes and phonemes*

Abstract Frequency of occurrence of words in a language is well described by Zipf's law. However, Zipf's law does not describe the distribution of the letters or phonemes from which words are composed. Examination of 32 text corpora from 18 languages shows that both letter and phoneme frequencies are well described by an equation first developed by Yule and by a parameter‐free equation that also describes the distribution of DNA codons.

Signal sequences containing multiple aromatic residues

Using homopolymeric units of either phenylalanine or tryptophan to replace the natural core segment of the Escherichia coli alkaline phosphatase signal peptide, the hydrophobicity requirements for protein export and processing were further explored. The mutant signal peptide containing polyphenylalanine functioned at least as efficiently as the wild-type, while the signal incorporating polytryptophan was dysfunctional. The transport properties of these mutants confirm our work with sequences rich in aliphatic residues; namely that a high mean hydrophobicity per residue is critical for complete and rapid precursor processing and for translocation of the protein. The efficient transport properties of the polyphenylalanine-containing signal peptide demonstrate that neither the bulky, aromatic nature of phenylalanine nor the unusually high hydrophobicity of this mutant peptide adversely alters function. This study also suggests that the low occurrence of phenylalanine in natural signal sequences is not of functional consequence but probably reflects the low number of DNA codons for this residue. The polytryptophan-containing precursor was membrane inserted but not translocated. This type of transport defect suggests that this is a weakly hydrophobic signal peptide, consistent with hydropathy scales, which indicate that tryptophan is comparable to alanine. This application of polymeric sequences provides a function-based assay for the evaluation of amino acid hydrophobicity.