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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 ISSN 1752-0509.

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Official URL: http://dx.doi.org/10.1186/1752-0509-7-108

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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
Subjects: Q Science > QH Natural history > QH301 Biology
Q Science > QH Natural history > QH426 Genetics
Divisions: Faculty of Science, Engineering and Medicine > 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:
DateEvent
2013Published
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 (Creative Commons)
Date of first compliant deposit: 26 December 2015
Date of first compliant Open Access: 26 December 2015
Funder: Seventh Framework Programme (European Commission) (FP7)
Grant number: FP7-ICT-FET-043338, FP7-ICT-FET 610730 (FP7)

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