Genetic and epigenetic mechanisms underlying cell-surface variability in protozoa and fungi

Eukaryotic microorganisms have evolved ingenious mechanisms to generate variability at their cell surface, permitting differential adherence, rapid adaptation to changing environments, and evasion of immune surveillance. Fungi such as Saccharomyces cerevisiae and the pathogen Candida albicans carry a family of mucin and adhesin genes that allow adhesion to various surfaces and tissues. Trypanosoma cruzi, T. brucei, and Plasmodium falciparum likewise contain large arsenals of different cell surface adhesion genes. In both yeasts and protozoa, silencing and differential expression of the gene family results in surface variability. Here, we discuss unexpected similarities in the structure and genomic location of the cell surface genes, the role of repeated DNA sequences, and the genetic and epigenetic mechanisms-all of which contribute to the remarkable cell surface variability in these highly divergent microbes.