mutation landscape

Brown KM, DePristo MA, Weinreich DM & Hartl DL 2009 Temporal constraints on the incorporation of regulatory mutants in evolutionary pathways. Mol Biol Evol 26:2455-2462.

• regulatory mutations often precede structural ones in enzyme evolution
• cryptic genes for the metabolism of certain substrates reside unexpressed in microbial genomes until mutationally activated by promoter mutations
• the initial substitution in an adaptive landscape is predicted to account for ~30% of the total fitness increase
• these observations suggest that regulatory mutations play a key role in enzyme evolution
• "regulation first" has some notable exceptions

• the effect of increased expression on drug resistance was highly dependent on the TEM structural gene (fig. 2)

• research continues to focus on the genetic sources of evolutionary novelty
• understanding which mutations are likely to create evolutionary novelty may require knowledge of the specific selective forces acting on enzyme activity at any one moment in time