Refactoring bacteriophage T7.
Natural biological systems are selected by evolution to continue to exist and evolve. Evolution likely gives rise to complicated systems that are difficult to understand and manipulate. Here, we redesign the genome of a natural biological system, bacteriophage T7, in order to specify an engineered surrogate that, if viable, would be easier to study and extend. Our initial design goals were to physically separate and enable unique manipulation of primary genetic elements. Implicit in our design are the hypotheses that overlapping genetic elements are, in aggregate, nonessential for T7 viability and that our models for the functions encoded by elements are sufficient. To test our initial design, we replaced the left 11,515 base pairs (bp) of the 39,937 bp wild-type genome with 12,179 bp of engineered DNA. The resulting chimeric genome encodes a viable bacteriophage that appears to maintain key features of the original while being simpler to model and easier to manipulate. The viability of our initial design suggests that the genomes encoding natural biological systems can be systematically redesigned and built anew in service of scientific understanding or human intention.
Chan
Leon Y
LY
Department of Biology, Massachusetts Institute of Technology, Cambridge, MA 02139, USA.
Kosuri
Sriram
S
Endy
Drew
D
D000465:Algorithms; D017123:Bacteriophage T7 / Q000235:genetics* / Q000254:growth & development / Q000502:physiology; D020029:Base Pairing; D004274:DNA, Recombinant / Q000138:chemical synthesis / Q000235:genetics; D004279:DNA, Viral / Q000235:genetics; D004926:Escherichia coli / Q000821:virology; D005807:Genes, Overlapping; D005814:Genes, Viral; D005818:Genetic Engineering; D016679:Genome, Viral; D008954:Models, Biological; D008957:Models, Genetic; D008969:Molecular Sequence Data; D030781:Organisms, Genetically Modified / Q000235:genetics / Q000254:growth & development / Q000502:physiology*; D017384:Sequence Deletion; D049490:Systems Biology / Q000379:methods*; D014162:Transfection; D014764:Viral Proteins / Q000235:genetics / Q000502:physiology; D014779:Virus Replication
D004274:DNA, Recombinant; D004279:DNA, Viral; D014764:Viral Proteins