Related Experiment Video
Updated: Jun 23, 2025
07:00
qPCRTag Analysis - A High Throughput, Real Time PCR Assay for Sc2.0 Genotyping
Published on: May 25, 2015
17.1K
Synthetic genomes unveil the effects of synonymous recoding
Akos Nyerges1, Anush Chiappino-Pepe1, Bogdan Budnik2
1Department of Genetics, Harvard Medical School, Boston, MA 02115, USA.
Biorxiv : the Preprint Server for Biology
|June 25, 2024
Summary
Scientists engineered a synthetic Escherichia coli genome using fewer codons, overcoming lethality from genetic code changes. This work enables safer genetically modified organisms and novel biopolymer production.
Area of Science:
- Synthetic biology
- Genomics
- Molecular biology
Background:
- Engineering organismal genetic codes enables virus resistance, containment of modified genes, and production of unnatural polymers.
- Reassigning codons is crucial for these goals but often lethal, with impacts on fitness poorly understood.
Purpose of the Study:
- To explore the fitness consequences of synonymous codon reassignment (recoding).
- To develop a workflow for constructing and troubleshooting synthetic genomes.
- To enable the creation of organisms with enhanced genetic properties.
Main Methods:
- Whole-genome synthesis and multiplexed directed evolution were employed.
- Genome-transcriptome-translatome-proteome co-profiling was used to analyze recoded genomes.
- A data-driven, multi-omics-based workflow was developed to address synthetic genome challenges.
Main Results:
- A synthetic Escherichia coli genome using 57 codons was assembled, overcoming lethality from 62,007 synonymous codon swaps.
- Synonymous recoding was found to induce transcriptional noise, including antisense RNAs, perturbing the transcriptome and proteome.
- Eliminating codons revealed cryptic promoters, suggesting natural codon usage minimizes transcriptional noise.
Conclusions:
- Synonymous codon choice significantly impacts organismal fitness and genome stability.
- The developed workflow successfully troubleshoots synthetic genome construction.
- This research paves the way for engineered organisms with genetic firewalls and expanded biosynthetic capabilities.
Related Concept Videos
02:55Synthetic Biology
4.7K
Synthetic biology is an interdisciplinary science that involves using principles from disciplines such as engineering, molecular biology, cell biology, and systems biology. It involves remodeling existing organisms from nature or constructing completely new synthetic organisms for applications such as protein or enzyme production, bioremediation, value-added macromolecule production, and the addition of desirable traits to crops, to name a few.
Golden rice
Golden rice is a genetically modified...
Golden rice
Golden rice is a genetically modified...
4.7K
02:08Gene Conversion
9.7K
Other than maintaining genome stability via DNA repair, homologous recombination plays an important role in diversifying the genome. In fact, the recombination of sequences forms the molecular basis of genomic evolution. Random and non-random permutations of genomic sequences create a library of new amalgamated sequences. These newly formed genomes can determine the fitness and survival of cells. In bacteria, homologous and non-homologous types of recombination lead to the evolution of new...
9.7K
02:53Conservative Site-specific Recombination and Phase Variation
6.0K
Because the DNA segments are cut and reorganized in a direction-specific manner, site-specific recombination has emerged as an efficient genetic engineering technique. Flippase and Cyclization recombinases or Flp and Cre, respectively, are two members of the tyrosine recombinase family derived from bacteriophages, that are used to mediate site-specific DNA insertions, deletions, and targeted expression of proteins in mammalian cell lines.
The recognition sites for Cre recombinase called LoxP...
The recognition sites for Cre recombinase called LoxP...
6.0K
02:05Gene Evolution - Fast or Slow?
7.1K
The genomes of eukaryotes are punctuated by long stretches of sequence which do not code for proteins or RNAs. Although some of these regions do contain crucial regulatory sequences, the vast majority of this DNA serves no known function. Typically, these regions of the genome are the ones in which the fastest change, in evolutionary terms, is observed, because there is typically little to no selection pressure acting on these regions to preserve their sequences.
In contrast, regions which code...
In contrast, regions which code...
7.1K
03:00Next-generation Sequencing
88.6K
The first human genome sequencing project cost $2.7 billion and was declared complete in 2003, after 15 years of international cooperation and collaboration between several research teams and funding agencies. Today, with the advent of next-generation sequencing technologies, the cost and time of sequencing a human genome have dropped over 100 fold.
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
Next-Generation Sequencing Methods
Although all next-generation methods use different technologies, they all share a set of standard features....
88.6K
02:46Genome Copying Errors
4.2K
DNA replication is a well-evolved process that copies millions of base pairs with high fidelity during each cell division. Occasionally a wrong base or a long stretch of wrong bases may get added to the daughter strands. If the errors are left unchecked, cells might accumulate several mutations that might endanger their survival. Therefore, the copying errors are checked and repaired at three levels.
4.2K