Arbitrariness in the genetic code is one of the main reasons for a linguistic approach to molecular biology: the genetic code is usually understood as an arbitrary relation between amino acids and nucleobases. However, from a semiotic point of view, arbitrariness should not be the only condition for definition of a code, consequently it is not completely correct to talk about "code" in this case. Yet we suppose that there exist a code in the process of protein synthesis, but on a higher level than the nucleic bases chains. Semiotically, a code should be always associated with a function and we propose to define the genetic code not only relationally (in basis of relation between nucleobases and amino acids) but also in terms of function (function of a protein as meaning of the code). Even if the functional definition of meaning in the genetic code has been discussed in the field of biosemiotics, its further implications have not been considered. In fact, if the function of a protein represents the meaning of the genetic code (the sign's object), then it is crucial to reconsider the notion of its expression (the sign) as well. In our contribution, we will show that the actual model of the genetic code is not the only possible and we will propose a more appropriate model from a semiotic point of view.
Recent years have seen a great expansion in our understandings of how silent mutations can drive a disease and that mRNAs are not only mere messengers between the genome and the encoded proteins but also encompass regulatory activities. This review focuses on how silent mutations within open reading frames can affect the functional properties of the encoded protein. We describe how mRNAs exert control of cell biological processes governed by the encoded proteins via translation kinetics, protein folding, mRNA stability, spatio-temporal protein expression and by direct interactions with cellular factors. These examples illustrate how additional levels of information lie within the coding sequences and that the degenerative genetic code is not redundant and have co-evolved with the encoded proteins. Hence, so called synonymous mutations are not always silent but 'whisper'.
- MeSH
- Genetic Code genetics MeSH
- Codon genetics MeSH
- Humans MeSH
- RNA, Messenger chemistry genetics MeSH
- Models, Genetic MeSH
- Mutation * MeSH
- Open Reading Frames genetics MeSH
- Proteins chemistry genetics metabolism MeSH
- Protein Biosynthesis genetics MeSH
- Protein Folding MeSH
- RNA Folding MeSH
- RNA Stability genetics MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
BACKGROUND: Almost all extant organisms use the same, so-called canonical, genetic code with departures from it being very rare. Even more exceptional are the instances when a eukaryote with non-canonical code can be easily cultivated and has its whole genome and transcriptome sequenced. This is the case of Blastocrithidia nonstop, a trypanosomatid flagellate that reassigned all three stop codons to encode amino acids. RESULTS: We in silico predicted the metabolism of B. nonstop and compared it with that of the well-studied human parasites Trypanosoma brucei and Leishmania major. The mapped mitochondrial, glycosomal and cytosolic metabolism contains all typical features of these diverse and important parasites. We also provided experimental validation for some of the predicted observations, concerning, specifically presence of glycosomes, cellular respiration, and assembly of the respiratory complexes. CONCLUSIONS: In an unusual comparison of metabolism between a parasitic protist with a massively altered genetic code and its close relatives that rely on a canonical code we showed that the dramatic differences on the level of nucleic acids do not seem to be reflected in the metabolisms. Moreover, although the genome of B. nonstop is extremely AT-rich, we could not find any alterations of its pyrimidine synthesis pathway when compared to other trypanosomatids. Hence, we conclude that the dramatic alteration of the genetic code of B. nonstop has no significant repercussions on the metabolism of this flagellate.
- MeSH
- Eukaryota genetics MeSH
- Genetic Code MeSH
- Parasites * genetics MeSH
- Codon, Terminator MeSH
- Trypanosoma brucei brucei * genetics MeSH
- Trypanosomatina * genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article MeSH
The site-specific chemical modification of proteins through incorporation of noncanonical amino acids enables diverse applications, such as imaging, probing, and expanding protein functions, as well as to precisely engineer therapeutics. Here we report a general strategy that allows the incorporation of noncanonical amino acids into target proteins using the amber suppression method and their efficient secretion in the biotechnological relevant expression host Bacillus subtilis. This facilitates efficient purification of target proteins directly from the supernatant, followed by their functionalization using click chemistry. We used this strategy to site-specifically introduce norbornene lysine into a single chain antibody and functionalize it with fluorophores for the detection of human target proteins.
- MeSH
- Bacillus subtilis genetics metabolism MeSH
- Click Chemistry MeSH
- CRISPR-Cas Systems MeSH
- Enzyme-Linked Immunosorbent Assay MeSH
- Genetic Vectors MeSH
- Genetic Code MeSH
- Isopropyl Thiogalactoside pharmacology MeSH
- Creatine Kinase, MM Form metabolism MeSH
- Humans MeSH
- Lysine chemistry MeSH
- Norbornanes chemistry MeSH
- Protein Engineering methods MeSH
- Gene Expression Regulation, Bacterial drug effects MeSH
- Recombinant Proteins chemistry genetics isolation & purification metabolism MeSH
- Green Fluorescent Proteins genetics metabolism MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
... Contents -- Preface to the Paperback Edition vii -- PART I HISTORY, POLITICS, AND GENETICS -- 1 Out of ... ... Science and Technology Behind Gene Mapping and Sequencing • Horace Freeland Judson 37 -- PART II GENETICS ... ... Watson 164 vi -- Contents -- PART III LTHICS, LAW, AND SOCIETY -- 8 The Social Power of Genetic Information ... ... Clairvoyance and Caution: Repercussions from the -- Human Genome Project • Nancy Wexler 211 -- 11 Genetic ... ... Autonomy • Ruth Schwartz Cowan 244 -- 12 Health Insurance, Employment Discrimination, and the Genetics ...
x, 397 s. : il. ; 24 cm
- Conspectus
- Obecná genetika. Obecná cytogenetika. Evoluce
- NML Fields
- genetika, lékařská genetika
- biologie
A limited number of non-canonical genetic codes have been described in eukaryotic nuclear genomes. Most involve reassignment of one or two termination codons as sense ones [1-4], but no code variant is known that would have reassigned all three termination codons. Here, we describe such a variant that we discovered in a clade of trypanosomatids comprising nominal Blastocrithidia species. In these protists, UGA has been reassigned to encode tryptophan, while UAG and UAA (UAR) have become glutamate encoding. Strikingly, UAA and, less frequently, UAG also serve as bona fide termination codons. The release factor eRF1 in Blastocrithidia contains a substitution of a conserved serine residue predicted to decrease its affinity to UGA, which explains why this triplet can be read as a sense codon. However, the molecular basis for the dual interpretation of UAR codons remains elusive. Our findings expand the limits of comprehension of one of the fundamental processes in molecular biology.
- MeSH
- Cell Nucleus genetics MeSH
- Phylogeny MeSH
- Genetic Code genetics MeSH
- Codon chemistry genetics MeSH
- Protozoan Proteins chemistry genetics MeSH
- Amino Acid Sequence MeSH
- Codon, Terminator chemistry genetics MeSH
- Trypanosomatina genetics MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
