Promiscuity, Serendipity and Metabolic Innovation
The proteomes of most bacteria contain 1000-2000 enzymes, and each enzyme has an unknown number of promiscuous activities. Consequently, bacteria can access many thousands of catalytic activities when a new enzyme is needed to enhance fitness or even to enable survival. We are interested in the potential for evolution of novel metabolic pathways patched together from multiple promiscuous enzymes.
Evolution in Action: An Evolving Metabolic Pathway for Degradation of a Toxic Pesticide
In the early 20th century, numerous anthropogenic chlorinated chemicals such as DDT, lindane, PCP, atrazine, tetrachloroethylene, and PCBs were introduced with little concern over their ultimate fate in the environment. Many of these compounds persist in the environment, posing risks to the health of humans and wildlife. We are interested in the assembly of new metabolic pathways that allow microbes to degrade recalcitrant and toxic pesticides.
Evolution of a New Enzyme by Gene Duplication and Divergence
We are interested in the trajectories by which microbes evolve improved fitness when a newly recruited promiscuous enzyme limits growth rate. New enzymes often evolve from promiscuous activities of previously existing enzymes by a process of gene duplication and divergence. This process is complicated by numerous factors, including the need to maintain the original function of the enzyme and the occurrence of mutations elsewhere in the genome that improve fitness by other mechanisms.
Synonymous ≠ Silent
Synonymous mutations have traditionally been considered to be silent with respect to fitness because they do not change the encoded amino acid. However, synonymous mutations can alter the mRNA structures in ways that alter translation initiation, mRNA stability, or even protein folding due to changes in the tempo of translation. We are interested in how synonymous mutations improve fitness when bacteria are subjected to strong selective pressures.