article published yes Magdalena Steinrück author 2C023F40-F248-11E8-B48F-1D18A9856A870000-0003-1229-9719 Calin C Guet author 47F8433E-F248-11E8-B48F-1D18A9856A870000-0001-6220-2052 CaGu department How the organization of genes on a chromosome shapes adaptation is essential for understanding evolutionary paths. Here, we investigate how adaptation to rapidly increasing levels of antibiotic depends on the chromosomal neighborhood of a drug-resistance gene inserted at different positions of the Escherichia coli chromosome. Using a dual-fluorescence reporter that allows us to distinguish gene amplifications from other up-mutations, we track in real-time adaptive changes in expression of the drug-resistance gene. We find that the relative contribution of several mutation types differs systematically between loci due to properties of neighboring genes: essentiality, expression, orientation, termination, and presence of duplicates. These properties determine rate and fitness effects of gene amplification, deletions, and mutations compromising transcriptional termination. Thus, the adaptive potential of a gene under selection is a system-property with a complex genetic basis that is specific for each chromosomal locus, and it can be inferred from detailed functional and genomic data. https://research-explorer.ista.ac.at/download/704/4975/IST-2017-890-v1+1_elife-25100-v1.pdf application/pdfno https://research-explorer.ista.ac.at/download/704/4976/IST-2017-890-v1+2_elife-25100-figures-v1.pdf application/pdfno eLife Sciences Publications2017 eng 2050-084X 00040618370000110.7554/eLife.25100 6 https://research-explorer.ista.ac.at/record/5564 https://research-explorer.ista.ac.at/record/26 Steinrück M, Guet CC. 2017. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. eLife. 6, e25100. Steinrück, Magdalena, and Calin C Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” <i>ELife</i>. eLife Sciences Publications, 2017. <a href="https://doi.org/10.7554/eLife.25100">https://doi.org/10.7554/eLife.25100</a>. M. Steinrück, C.C. Guet, ELife 6 (2017). Steinrück, Magdalena, and Calin C. Guet. “Complex Chromosomal Neighborhood Effects Determine the Adaptive Potential of a Gene under Selection.” <i>ELife</i>, vol. 6, e25100, eLife Sciences Publications, 2017, doi:<a href="https://doi.org/10.7554/eLife.25100">10.7554/eLife.25100</a>. Steinrück, M., &#38; Guet, C. C. (2017). Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. <i>ELife</i>. eLife Sciences Publications. <a href="https://doi.org/10.7554/eLife.25100">https://doi.org/10.7554/eLife.25100</a> Steinrück M, Guet CC. Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection. <i>eLife</i>. 2017;6. doi:<a href="https://doi.org/10.7554/eLife.25100">10.7554/eLife.25100</a> M. Steinrück and C. C. Guet, “Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection,” <i>eLife</i>, vol. 6. eLife Sciences Publications, 2017. 7042018-12-11T11:48:01Z2026-04-21T22:30:55Z