Complex chromosomal neighborhood effects determine the adaptive potential of a gene under selection.
Magdalena SteinrueckCălin C GuetPublished in: eLife (2017)
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.
Keyphrases
- copy number
- genome wide
- genome wide identification
- escherichia coli
- dna methylation
- poor prognosis
- physical activity
- genome wide analysis
- transcription factor
- gene expression
- machine learning
- binding protein
- risk assessment
- crispr cas
- long non coding rna
- electronic health record
- pseudomonas aeruginosa
- oxidative stress
- klebsiella pneumoniae
- multidrug resistant
- genome wide association study