Transcriptional differences in polymorphic and conserved domains of a complete cloned P. falciparum chromosome

Classical genetic studies on the human malaria parasite Plasmodium falciparum have been hampered by a complex life cycle which alternates between vertebrate and invertebrate hosts. Consequently, only a few genetic crosses have been performed so far. In addition, molecular genetics has provided only limited access to the genes of this pathogen, a consequence of an unusually high A + T content. To overcome these limitations we have constructed an ordered telomere-to-telomere contig map of P. falciparum chromosome 2 by isolating overlapping yeast artificial chromosome clones. This approach was used to examine the strain-dependent polymorphisms commonly observed for P. falciparum chromosomes. Our analysis reveals that polymorphisms of chromosome 2 are restricted to regions at either end, representing 20% of the chromosome. Transcription mapping of the entire chromosome suggests a compartmentalization of chromosome 2 into a transcribed central domain and silent polymorphic ends.