From silent genes to noisy populations-dialogue between the genotype and phenotypes of antigenic variation.

African trypanosomes evade humoral immunity through antigenic variation whereby, they switch expression of the variant surface glycoprotein (VSG) gene encoding their glycoprotein surface coat. Switching proceeds by duplication from an archive of silent VSG genes into a transcriptionally active locus, and precedent suggests silent genes can contribute, combinatorially to formation of expressed, functional genes through segmental gene conversion. The genome project has revealed that most of the silent archive consists of hundreds of VSG genes in subtelomeric tandem arrays, and that most of these are not functional genes. The aim of this review is to explore links between the uncovered trypanosome genotype and the phenotype of antigenic variation, stretching from the broad phenotype-transmission in the field and the overcoming of herd immunity-to events within single infections. Highlighting in particular the possible impact of phenotype selection on the evolution of the VSG archive and the mechanisms for its expression leads to a theoretical framework to further our understanding of this complex immune evasion strategy.