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Results for “Genetic code expansion”

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23 records · Page 2

Split aminoacyl-tRNA synthetases for proximity-induced stop codon suppression

Synthetic biology tools for regulating gene expression have many useful biotechnology and therapeutic applications. Most tools developed for this purpose control gene expression at the level of transcription, and relatively few methods are available for regulating gene expression at the translational level. Here, we design and engineer split orthogonal aminoacyl-tRNA synthetases (o-aaRS) as unique tools to control gene translation in bacteria and mammalian cells. Using chemically induced dimerization domains, we developed split o-aaRSs that mediate gene expression by conditionally suppressing stop codons in the presence of the small molecules rapamycin and abscisic acid. Furthermore, by activating o-aaRSs, these molecular switches induce stop codon suppression, and in their absence stop codon suppression is turned off. We demonstrate, in Escherichia coli and in human cells, that split o-aaRSs function as genetically encoded AND gates where stop codon suppression is controlled by two distinct molecular inputs. In addition, we show that split o-aaRSs can be used as versatile biosensors to detect therapeutically relevant protein–protein interactions, including those involved in cancer, and those that mediate severe acute respiratory syndrome-coronavirus-2 infection.

59 BASIC BIOLOGICAL SCIENCES↗

Unconventional genetic code systems in archaea

Archaea constitute the third domain of life, distinct from bacteria and eukaryotes given their ability to tolerate extreme environments. To survive these harsh conditions, certain archaeal lineages possess unique genetic code systems to encode either selenocysteine or pyrrolysine, rare amino acids not found in all organisms. Furthermore, archaea utilize alternate tRNA-dependent pathways to biosynthesize and incorporate members of the 20 canonical amino acids. Recent discoveries of new archaeal species have revealed the co-occurrence of these genetic code systems within a single lineage. This review discusses the diverse genetic code systems of archaea, while detailing the associated biochemical elements and molecular mechanisms.

59 BASIC BIOLOGICAL SCIENCES↗

Adaptive gene loss in the common bean pan-genome during range expansion and domestication

The common bean ( Phaseolus vulgaris L.) is a crucial legume crop and an ideal evolutionary model to study adaptive diversity in wild and domesticated populations. Here, we present a common bean pan-genome based on five high-quality genomes and whole-genome reads representing 339 genotypes. It reveals ~234 Mb of additional sequences containing 6,905 protein-coding genes missing from the reference, constituting 49% of all presence/absence variants (PAVs). More non-synonymous mutations are found in PAVs than core genes, probably reflecting the lower effective population size of PAVs and fitness advantages due to the purging effect of gene loss. Our results suggest pan-genome shrinkage occurred during wild range expansion. Selection signatures provide evidence that partial or complete gene loss was a key adaptive genetic change in common bean populations with major implications for plant adaptation. The pan-genome is a valuable resource for food legume research and breeding for climate change mitigation and sustainable agriculture.

59 BASIC BIOLOGICAL SCIENCES↗

Phylogenomics and Comparative Genomics Highlight Specific Genetic Features in Ganoderma Species

The Ganoderma species in Polyporales are ecologically and economically relevant wood decayers used in traditional medicine, but their genomic traits are still poorly documented. In the present study, we carried out a phylogenomic and comparative genomic analyses to better understand the genetic blueprint of this fungal lineage. We investigated seven Ganoderma genomes, including three new genomes, G. australe, G. leucocontextum, and G. lingzhi. The size of the newly sequenced genomes ranged from 60.34 to 84.27 Mb and they encoded 15,007 to 20,460 genes. A total of 58 species, including 40 white-rot fungi, 11 brown-rot fungi, four ectomycorrhizal fungi, one endophyte fungus, and two pathogens in Basidiomycota, were used for phylogenomic analyses based on 143 single-copy genes. It confirmed that Ganoderma species belong to the core polyporoid clade. Comparing to the other selected species, the genomes of the Ganoderma species encoded a larger set of genes involved in terpene metabolism and coding for secreted proteins (CAZymes, lipases, proteases and SSPs). Of note, G. australe has the largest genome size with no obvious genome wide duplication, but showed transposable elements (TEs) expansion and the largest set of terpene gene clusters, suggesting a high ability to produce terpenoids for medicinal treatment. G. australe also encoded the largest set of proteins containing domains for cytochrome P450s, heterokaryon incompatibility and major facilitator families. Besides, the size of G. australe secretome is the largest, including CAZymes (AA9, GH18, A01A), proteases G01, and lipases GGGX, which may enhance the catabolism of cell wall carbohydrates, proteins, and fats during hosts colonization. The current genomic resource will be used to develop further biotechnology and medicinal applications, together with ecological studies of the Ganoderma species.

59 BASIC BIOLOGICAL SCIENCES↗

Four principles to establish a universal virus taxonomy

A universal taxonomy of viruses is essential for a comprehensive view of the virus world and for communicating the complicated evolutionary relationships among viruses. However, there are major differences in the conceptualisation and approaches to virus classification and nomenclature among virologists, clinicians, agronomists, and other interested parties. Here, we provide recommendations to guide the construction of a coherent and comprehensive virus taxonomy, based on expert scientific consensus. Firstly, assignments of viruses should be congruent with the best attainable reconstruction of their evolutionary histories, i.e., taxa should be monophyletic. This fundamental principle for classification of viruses is currently included in the International Committee on Taxonomy of Viruses (ICTV) code only for the rank of species. Secondly, phenotypic and ecological properties of viruses may inform, but not override, evolutionary relatedness in the placement of ranks. Thirdly, alternative classifications that consider phenotypic attributes, such as being vector-borne (e.g., “arboviruses”), infecting a certain type of host (e.g., “mycoviruses,” “bacteriophages”) or displaying specific pathogenicity (e.g., “human immunodeficiency viruses”), may serve important clinical and regulatory purposes but often create polyphyletic categories that do not reflect evolutionary relationships. Nevertheless, such classifications ought to be maintained if they serve the needs of specific communities or play a practical clinical or regulatory role. However, they should not be considered or called taxonomies. Finally, while an evolution-based framework enables viruses discovered by metagenomics to be incorporated into the ICTV taxonomy, there are essential requirements for quality control of the sequence data used for these assignments. Combined, these four principles will enable future development and expansion of virus taxonomy as the true evolutionary diversity of viruses becomes apparent.

59 BASIC BIOLOGICAL SCIENCES↗