The human malaria parasite, Plasmodium falciparum, maintains a persistent infection altering the proteins expressed on the surface of the infected red blood cells, thus avoiding the host immune response. The primary surface antigen, a protein called PfEMP1, is encoded by a multicopy gene family called var. Each individual parasite only expresses a single var gene at a time, maintaining all other members of the family in a transcriptionally silent state. Previous work using reporter genes in transiently transfected plasmid constructs implicated a conserved intron found in all var genes in the silencing process. Here we have utilized episomal recombination within stably transformed parasites to generate different var promoter and intron arrangements and show that loss of the intron results in var promoter activation. Further, in multicopy plasmid concatamers, each intron could only silence a single promoter, suggesting a one-to-one pairing requirement for silencing. Transcriptionally active, "unpaired" promoters remained active after integration into a chromosome; however, they were not recognized by the pathway that maintains mutually exclusive var gene expression. The data indicate that intron/promoter pairing is responsible for silencing each individual var gene and that disruption of silencing of one gene does not affect the transcriptional activity of neighboring var promoters. This suggests that silencing is regulated at the level of individual genes rather than by assembly of silent chromatin throughout a chromosomal region, thus providing a possible explanation of how a var gene can be maintained in a silent state while the immediately adjacent var gene is transcriptionally active.

The human malaria parasite Plasmodium falciparum utilizes a mechanism of antigenic variation to avoid the antibody response of its human host and thereby generates a long-term, persistent infection. This process predominantly results from systematic changes in expression of the primary erythrocyte surface antigen, a parasite-produced protein called PfEMP1 that is encoded by a repertoire of over 60 var genes in the P. falciparum genome. var genes exhibit extensive sequence diversity, both within a single parasite's genome as well as between different parasite isolates, and thus provide a large repertoire of antigenic determinants to be alternately displayed over the course of an infection. While significant work has recently been published documenting the extreme level of diversity displayed by var genes found in natural parasite populations, little work has been done regarding the mechanisms that lead to sequence diversification and heterogeneity within var genes. In the course of producing transgenic lines from the original NF54 parasite isolate, we cloned and characterized a parasite line, termed E5, which is closely related to but distinct from 3D7, the parasite used for the P. falciparum genome nucleotide sequencing project. Analysis of the E5 var gene repertoire, as well as that of the surrounding rif and stevor multi-copy gene families, identified examples of frequent recombination events within these gene families including an example of a duplicative transposition indicating recombination events play a significant role in the generation of diversity within the antigen encoding genes of P. falciparum.

The Meran-Mauls nappe stack is part of the Austroalpine unit in South Tyrol (Italy). There it holds a special position directly in front of the Southalpine Dolomites indenter and west of the Tauern Window. It is situated in the hanging wall of the Southalpine unit, above a NW dipping segment of the Periadriatic fault system, namely the Meran-Mauls fault. Also all other sides are defined by Oligocene-Miocene strike-slip and normal faults. Based on recent mapping the Meran-Mauls nappe stack consists of three nappes separated by NW to NNW dipping shear zones. The lowermost nappe in the southwest is represented by the Schenna (Scena) unit. It is overlain along the Masul shear zone by a nappe consisting of the Hirzer (Punta Cervina) unit and the Pens (Pennes) unit including Triassic (meta)sediments. Separated by the Fartleis fault the St. Leonhard (San Leonardo) unit forms the uppermost nappe. The aim of this study is to describe the individual units and the separating structural elements more properly, based on new structural, petrological, geothermobarometric and geochronological data and to compare these units to other Austroalpine elements in the vicinity. Sillimanite-bearing paragneiss, minor amphibolite and quartzite as well as a distinct marble layer close to its base characterise the Schenna unit. Further, it contains pegmatite dikes, presumably Permian in age. Amphibolite-facies P-T conditions of c. 0.55 ± 0.15 GPa and 600 ± 100°C are thus correlated with a Permian metamorphic imprint. The Masul shear zone mostly consists of mylonitic paragneiss of the Hirzer unit. It is pre-Alpine in age and probably formed during the Jurassic. For the paragneiss of the Hirzer unit upper greenschist- to amphibolite-facies metamorphic conditions of 0.4-0.50 ± 0.15 GPa and 550 ± 70°C are attributed to the Variscan tectonometamorphic imprint. The whole Pens unit represents a shear zone. Due to the occurrence of Permotriassic (meta)-sediments within this shear zone, it is an Alpine structure, as well as the bordering Fartleis fault. Rb/Sr biotite ages yield sometimes partly reset pre-Alpine age values in the whole Meran-Mauls nappe stack, indicating a pervasive anchizonal to lowermost greenschist-facies metamorphic overprint during the Eoalpine tectonometamorphic event. Tectonostratigraphically the Meran-Mauls nappe stack can be attributed to the Drauzug-Gurktal nappe system. The latter forms the uppermost structural element of the Austroalpine nappe stack and thus only shows a weak Eoalpine metamorphic overprint. With respect to its special lithologic composition the Schenna unit can be correlated with the Tonale unit in the southwest and the Strieden-Komplex in the east.