Adaptive constraints at the genomic and genic level in E. coli
Abstract: To uncover the molecular determinants of bacterial adaptation, we have used two alternatives approaches: one at the genome level and one at the gene level. At the genome level, whole genome sequencing of more than 100 lineages independently evolved to high temperature revealed that adaptation proceed through a large diversity of mutation events that affected a few functional targets. Moreover, statistical analysis of the distribution of mutations among lineages uncovered the presence of pervasive epistasis that constrained and shaped the adaptive path of the different populations. At the gene level, we produced, sequenced and phenotypes 10,000 random mutants in betalactamase TEM and studied the determinants of mutation effects on that enzyme. We showed that a biophysical model of protein stability could capture both mutation effects and epistatic interactions among mutations.