Design, synthesis, and testing toward a 57-codon genome.
نویسندگان
چکیده
Recoding--the repurposing of genetic codons--is a powerful strategy for enhancing genomes with functions not commonly found in nature. Here, we report computational design, synthesis, and progress toward assembly of a 3.97-megabase, 57-codon Escherichia coli genome in which all 62,214 instances of seven codons were replaced with synonymous alternatives across all protein-coding genes. We have validated 63% of recoded genes by individually testing 55 segments of 50 kilobases each. We observed that 91% of tested essential genes retained functionality with limited fitness effect. We demonstrate identification and correction of lethal design exceptions, only 13 of which were found in 2229 genes. This work underscores the feasibility of rewriting genomes and establishes a framework for large-scale design, assembly, troubleshooting, and phenotypic analysis of synthetic organisms.
منابع مشابه
Complete sequence of the amphioxus (Branchiostoma lanceolatum) mitochondrial genome: relations to vertebrates
The complete nucleotide sequence of the mitochondrial DNA of the amphioxus Branchiostoma lanceolatum has been determined. This mitochondrial genome is small (15 076 bp) because of the short size of the two rRNA genes and the tRNA genes. In addition, this genome contains a very short non-coding region (57 bp) with no sequence reminiscent of a control region. The organisation of the coding genes,...
متن کاملAn algorithmic framework for genome-wide modeling and analysis of translation networks.
The sequencing of genomes of several organisms and advances in high throughput technologies for transcriptome and proteome analysis has allowed detailed mechanistic studies of transcription and translation using mathematical frameworks that allow integration of both sequence-specific and kinetic properties of these fundamental cellular processes. To understand how perturbations in mRNA levels a...
متن کاملEuGene: maximizing synthetic gene design for heterologous expression
UNLABELLED Numerous software applications exist to deal with synthetic gene design, granting the field of heterologous expression a significant support. However, their dispersion requires the access to different tools and online services in order to complete one single project. Analyzing codon usage, calculating codon adaptation index (CAI), aligning orthologs and optimizing genes are just a fe...
متن کاملComparative bioinformatics analysis of a wild diploid Gossypium with two cultivated allotetraploid species
Background: Gossypium thurberi is a wild diploid species that has been used to improve cultivated allotetraploid cotton. G. thurberi belongs to D genome, which is an important wild bio-source for the cotton breeding and genetic research. To a certain degree, chloroplast DNA sequence information are a versatile tool for species identification and phylogenetic implications in plants. Different ch...
متن کاملComputational Tools and Algorithms for Designing Customized Synthetic Genes
Advances in DNA synthesis have enabled the construction of artificial genes, gene circuits, and genomes of bacterial scale. Freedom in de novo design of synthetic constructs provides significant power in studying the impact of mutations in sequence features, and verifying hypotheses on the functional information that is encoded in nucleic and amino acids. To aid this goal, a large number of sof...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
عنوان ژورنال:
- Science
دوره 353 6301 شماره
صفحات -
تاریخ انتشار 2016