Cellular ‘Gold’: Competition for Iron as the Cause of Reciprocal Positive Selection of Host and Pathogen Iron-Binding Proteins

Iron is a critical metal for essential cellular processes, such as respiration, in both human and microbial cells.  Thus, in the context of infection, iron is a high-value cellular commodity and an evolutionist might reasonably expect a metallic tug-of-war between host and pathogen iron-binding proteins or other iron-binding molecules (siderophores).  This speculation is impressively supported in a paper published this month (Barber and Elde, 2014).  These authors provide strong evidence for positive selection affecting several sites in host (transferrin, Tf) and pathogen (transferrin binding protein A) iron-binding proteins based on a combination of genetic, structural, and functional experimental methods. (more…)

Genomic Analysis of a Bacterial Evolutionary Pathway Underlying a Phenotypic Innovation

Peter and Rosemary Grant have been responsible for what must be among the longest-running continuous field studies in evolutionary biology (2011).  It will reach forty years in 2013.  In this work, the Grants closely follow multiple species of finches on the Galápagos Island of Daphne Major.  Their results have provided numerous valuable insights into the nature of evolutionary change. 

The closest comparable study in the laboratory setting, with respect to both duration and the number of insights pertaining to the nature of selection and evolution, is perhaps the Long-Term Evolutionary Experiment (LTEE) of Richard Lenski and his associates at Michigan State University.  For almost twenty-five years they have been growing twelve populations of Escherichia coli in a glucose-limited minimal medium and transferring a sample of each population to a fresh flask every day and freezing samples periodically for later analysis.  They have now propagated these bacteria for more than 40,000 generations. 

Under the well-aerated conditions of these cultures, E. coli cannot normally utilize the substantial amount of citrate in the medium as a carbon source.  However, mutation to a Cit+ phenotype did occur in one of the long-term populations after about 31,000 generations.  In a Nature paper published last month, Blount et al. (2012) thoroughly characterize the mutational steps required to achieve the Cit+ phenotype. (more…)

Continuous In Vitro Directed Evolution of Macromolecules

Evolutionary processes, and specifically selection-based mechanisms, have long served to inspire in vitro methods for generating proteins and nucleic acids that mediate functions of interest.  Examples going back two decades include the development of phage display methods (Scott and Smith, 1990) and methods based on selection of RNA molecules (Ellington and Szostak, 1990; Tuerk and Gold, 1990) from libraries of enormous  structural diversity (as many as1010 distinct molecular structures).  A recent review (Dreier and Plückthun, 2011) provides a sense of what can be accomplished with one these methods, ribosome display, in terms of generating macromolecules, such as antibody fragments, with desired functional properties (e.g., high-affinity binding to a target molecule).

However, (more…)

Evolutionary Erosion of Anti-Microbial Magic

In the early years of the last century, Paul Ehrlich coined the term “magic bullet” to indicate a therapeutic agent that targeted an infectious agent or tumor with exquisite specificity (Schwartz, 2004).  He was inspired by his work with antibodies to imagine a future age of impressively discriminating and extremely effective drugs.  Perhaps the class of therapeutic agents with the longest and most impressive record of illustrating this concept has been antibiotics.  However, as a recent example (Kumarasamy et al., 2010) from the vast and continuously growing literature on antibiotic resistance illustrates, the ever-expanding list of evolving mechanisms through which bacteria counteract the actions of these therapeutic agents has put their continuing effectiveness in jeopardy. (more…)