Evolution and Evolvability of Antigenic Variation

Dustin Brisson

Department of Biology, University of Pennsylvania, USA
dbrisson@sas.upenn.edu

The hypothesis that evolvability - the capacity to evolve by natural selection - is itself the object of natural selection is highly intriguing but remains controversial due in large part to a paucity of direct experimental evidence. The antigenic variation mechanisms of pathogens provide an ideal system to test whether natural selection has favored mechanisms that increase evolvability. This presentation outlines the evolvability controversy and provides empirical data in support of the hypothesis that natural selection can indeed favor greater evolvability using the Lyme disease bacterium, Borrelia burgdorferi, as a model system. The antigenic variation system of B. burgdorferi consists of many unexpressed ‘cassettes’ that recombine into the expression site (vlsE) to alter the sequence of the VlsE protein, primary surface antigen. As the magnitude of sequence change at vlsE is a function of the genetic diversity among the unexpressed cassettes, evidence that selection favors among-cassette diversity is direct evidence that natural selection promotes antigenic evolvability. We show that diversity among vls cassettes is favored by natural selection in each B. burgdorferi strain analyzed using both classical (dN/dS ratios) and Bayesian population genetic analyses of genetic sequence data. Diversification among vls cassettes due to natural selection promotes long-term antigenic evolvability of VlsE. These findings provide a direct demonstration that molecular mechanisms that enhance evolvability of surface antigens are an evolutionary adaptation.

Recent publications:

1. Graves, C, Ros VID, Stevenson B, Sniegowski P, Brisson D.  2013.  Natural selection promotes antigenic evolvability. PLoS Pathogens. 9(11):e1003766

2. Leichty, AR, Brisson D.  2014.  Selective Whole Genome Amplification for Re-Sequencing Target Microbial Species from Complex Natural Samples. Genetics. 198(2):473-481.

3. Zhou, W, Brisson D.  2014.  Potentially conflicting selective forces that shape the vls antigenic variation system in Borrelia burgdorferi. Infection, Genetics and Evolution. 27:559–565.