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Detecting positive selection from genome scans of linkage disequilibrium
Authors:Chad D Huff  Henry C Harpending  Alan R Rogers
Institution:1. Center for Bioinformatics Tübingen, Department of Information and Cognitive Sciences, University of Tübingen, Sand 14, D-72076, Tübingen, Germany
2. Department of Biotechnology, Norwegian University of Science and Technology (NTNU), Sem S?landsvei 6-8, N-7491, Trondheim, Norway
3. Department of Biotechnology, SINTEF Materials and Chemistry, Sem S?landsvei 2a, N-7465, Trondheim, Norway
4. Groningen Bioinformatics Centre, University of Groningen, Kerklaan 30, 9751, NN Haren, the Netherlands
5. Department of Microbial Physiology, University of Groningen, Kerklaan 30, 9751, NN Haren, the Netherlands
12. Warwick Systems Biology Centre, University of Warwick, Coventry House, CV4 7AL, Coventry, UK
11. Department of Biological Sciences, University of Warwick, Gibbet Hill Road, CV4 7AL, Coventry, UK
7. Instituto de Biotecnología de León, INBIOTEC, Parque Científico de León, Av. Real 1, 24006, León, Spain
8. área de Microbiología, Universidad de León, Spain
9. Department of Microbiology/Biotechnology, University of Tübingen, Auf der Morgenstelle 28, D-72076, Tübingen, Germany
10. School of Medical Sciences, Institute of Medical Sciences, University of Aberdeen, Foresterhill, AB25 2ZD, Aberdeen, UK
6. Department of Chemistry, University of Warwick, Gibbet Hill Road, CV4 7AL, Coventry, UK
13. Microarray Facility Tübingen, Calwer Strasse 7, D-72076, Tübingen, Germany
Abstract:

Background

During the lifetime of a fermenter culture, the soil bacterium S. coelicolor undergoes a major metabolic switch from exponential growth to antibiotic production. We have studied gene expression patterns during this switch, using a specifically designed Affymetrix genechip and a high-resolution time-series of fermenter-grown samples.

Results

Surprisingly, we find that the metabolic switch actually consists of multiple finely orchestrated switching events. Strongly coherent clusters of genes show drastic changes in gene expression already many hours before the classically defined transition phase where the switch from primary to secondary metabolism was expected. The main switch in gene expression takes only 2 hours, and changes in antibiotic biosynthesis genes are delayed relative to the metabolic rearrangements. Furthermore, global variation in morphogenesis genes indicates an involvement of cell differentiation pathways in the decision phase leading up to the commitment to antibiotic biosynthesis.

Conclusions

Our study provides the first detailed insights into the complex sequence of early regulatory events during and preceding the major metabolic switch in S. coelicolor, which will form the starting point for future attempts at engineering antibiotic production in a biotechnological setting.
Keywords:
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