Development and application of classical genetics in Toxoplasma gondii

Apicomplexan parasites have complex life cycles involving sexual replication in a single definitive host and asexual replication in a variety of alternative hosts. Toxoplasma gondii undergoes its sexual cycle only in cats, yet it also infects a wide range of other vertebrates where it propagates asexually. In Europe and North America the bulk of T. gondii infections are due to one of three major clonal lines (types 1, 2, and 3) which only recently originated from a few closely related parental lines. In South America, T. gondii strains exhibit significantly more genotypic diversity. Despite being genetically quite similar, even the North American clonal types differ substantially in various biological traits including virulence in laboratory mice, induction of changes in host-cell signaling, and transcription. The ability to perform experimental genetic crosses has been exploited extensively in the past 15 years, first to generate linkage maps to facilitate completion of the genome assembly, and then later to map traits differing in the parental lines to individual loci. This chapter will highlight the power of this approach to map both simple and complex biological traits, including drug resistance, replication rate, pathogenesis in laboratory mice, induction of host gene expression, and modulation of the immune response. The most exciting findings to emerge from this approach in T. gondii have been the unequivocal identification of families of secreted effectors that are capable of direct modulation of the host environment, including those capable of disrupting cell-autonomous immune responses and the recruitment of host organelles.