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Automated design of bacterial genome sequences
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Carrera, Javier and Jaramillo, Alfonso (2013) Automated design of bacterial genome sequences. BMC Systems Biology, Volume 7 (Number 1). Article number 108. doi:10.1186/1752-0509-7-108
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Official URL: http://dx.doi.org/10.1186/1752-0509-7-108
Abstract
Background:
Organisms have evolved ways of regulating transcription to better adapt to varying environments. Could the current functional genomics data and models support the possibility of engineering a genome with completely rearranged gene organization while the cell maintains its behavior under environmental challenges? How would we proceed to design a full nucleotide sequence for such genomes?
Results:
As a first step towards answering such questions, recent work showed that it is possible to design alternative transcriptomic models showing the same behavior under environmental variations than the wild-type model. A second step would require providing evidence that it is possible to provide a nucleotide sequence for a genome encoding such transcriptional model. We used computational design techniques to design a rewired global transcriptional regulation of Escherichia coli, yet showing a similar transcriptomic response than the wild-type. Afterwards, we “compiled” the transcriptional networks into nucleotide sequences to obtain the final genome sequence. Our computational evolution procedure ensures that we can maintain the genotype-phenotype mapping during the rewiring of the regulatory network. We found that it is theoretically possible to reorganize E. coli genome into 86% fewer regulated operons. Such refactored genomes are constituted by operons that contain sets of genes sharing around the 60% of their biological functions and, if evolved under highly variable environmental conditions, have regulatory networks, which turn out to respond more than 20% faster to multiple external perturbations.
Conclusions:
This work provides the first algorithm for producing a genome sequence encoding a rewired transcriptional regulation with wild-type behavior under alternative environments.
| Item Type: | Journal Article | ||||
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| Subjects: | Q Science > QH Natural history > QH301 Biology Q Science > QH Natural history > QH426 Genetics |
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| Divisions: | Faculty of Science > Life Sciences (2010- ) | ||||
| Library of Congress Subject Headings (LCSH): | Synthetic biology, Bioengineering, Genomes, Nucleotide sequence, Bacterial genetic engineering | ||||
| Journal or Publication Title: | BMC Systems Biology | ||||
| Publisher: | BioMed Central Ltd. | ||||
| ISSN: | 1752-0509 | ||||
| Official Date: | 2013 | ||||
| Dates: |
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| Volume: | Volume 7 | ||||
| Number: | Number 1 | ||||
| Page Range: | Article number 108 | ||||
| DOI: | 10.1186/1752-0509-7-108 | ||||
| Status: | Peer Reviewed | ||||
| Publication Status: | Published | ||||
| Access rights to Published version: | Open Access | ||||
| Funder: | Seventh Framework Programme (European Commission) (FP7) | ||||
| Grant number: | FP7-ICT-FET-043338, FP7-ICT-FET 610730 (FP7) |
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