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
BACKGROUND: Departures from the standard genetic code in eukaryotic nuclear genomes are known for only a handful of lineages and only a few genetic code variants seem to exist outside the ciliates, the most creative group in this regard. Most frequent code modifications entail reassignment of the UAG and UAA codons, with evidence for at least 13 independent cases of a coordinated change in the meaning of both codons. However, no change affecting each of the two codons separately has been documented, suggesting the existence of underlying evolutionary or mechanistic constraints. RESULTS: Here, we present the discovery of two new variants of the nuclear genetic code, in which UAG is translated as an amino acid while UAA is kept as a termination codon (along with UGA). The first variant occurs in an organism noticed in a (meta)transcriptome from the heteropteran Lygus hesperus and demonstrated to be a novel insect-dwelling member of Rhizaria (specifically Sainouroidea). This first documented case of a rhizarian with a non-canonical genetic code employs UAG to encode leucine and represents an unprecedented change among nuclear codon reassignments. The second code variant was found in the recently described anaerobic flagellate Iotanema spirale (Metamonada: Fornicata). Analyses of transcriptomic data revealed that I. spirale uses UAG to encode glutamine, similarly to the most common variant of a non-canonical code known from several unrelated eukaryotic groups, including hexamitin diplomonads (also a lineage of fornicates). However, in these organisms, UAA also encodes glutamine, whereas it is the primary termination codon in I. spirale. Along with phylogenetic evidence for distant relationship of I. spirale and hexamitins, this indicates two independent genetic code changes in fornicates. CONCLUSIONS: Our study documents, for the first time, that evolutionary changes of the meaning of UAG and UAA codons in nuclear genomes can be decoupled and that the interpretation of the two codons by the cytoplasmic translation apparatus is mechanistically separable. The latter conclusion has interesting implications for possibilities of genetic code engineering in eukaryotes. We also present a newly developed generally applicable phylogeny-informed method for inferring the meaning of reassigned codons.
- MeSH
- Cell Nucleus genetics MeSH
- Ciliophora genetics MeSH
- Phylogeny MeSH
- Genetic Code * MeSH
- Glutamine genetics MeSH
- Insecta parasitology MeSH
- Codon genetics MeSH
- Leucine genetics MeSH
- Evolution, Molecular MeSH
- Open Reading Frames genetics MeSH
- Rhizaria genetics MeSH
- Animals MeSH
- Check Tag
- Animals MeSH
- Publication type
- Journal Article 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
