Molecular & Biochemical Parasitology 127 (2003) 179–191 The 3D7var5.2 (var COMMON ) type var gene family is commonly expressed in non-placental Plasmodium falciparum malaria  Gerhard Winter a,b , Qijun Chen a,b , Kirsten Flick a,b,1 , Peter Kremsner c,d , Victor Fernandez a,b , Mats Wahlgren a,b,∗ a Microbiology and Tumor Biology Center, Karolinska Institutet, P.O. Box 280, SE-171 77 Stockholm, Sweden b Swedish Institute for Infectious Disease Control, SE-171 82 Stockholm, Sweden c Department of Parasitology, Institute of Tropical Medicine, University of Tubingen, Wilhelmstrasse 27, 72074 Tubingen, Germany d Medical Research Unit, Albert Schweitzer Hospital, Lambarene, Gabon Received 16 September 2002; received in revised form 5 November 2002; accepted 18 November 2002 Abstract Relapse variants in chronic Plasmodium falciparum infections are antigenically distinct from the parental parasites. The variable antigen PfEMP1 expressed at the surface of the infected erythrocyte (IE) is encoded by the var gene family with ≈60 copies per haploid genome. Placental isolates commonly express DBL containing subtypes of var genes with homology to either 3D7var5.2 (var COMMON ) or FCR3var CSA . Here we report that var COMMON related genes are constitutively transcribed in ≈60% of malaria infected children in Gabon. var COMMON is conserved in field isolates over at least 2.1 kb. In 3D7 parasites var COMMON is present on chromosome 5 (var5.2) and constitutively transcribed in the opposite direction to most other var genes. It lacks a regulatory intron, an acidic terminal segment and ends in telomeric repeat sequences. var COMMON encodes a large, hypothetical PfEMP1 of a structure similar to previous placenta-binding PfEMP1s but it is not present at the IE-surface. IE of a 3D7 clone (3D7S8) transcribe var COMMON but express a PfEMP1 distinct from var COMMON at the surface and adhere to placental tissues through var COMMON independent novel mechanisms. Our report suggests that expression of var COMMON type genes is not restricted to placental malaria. © 2003 Published by Elsevier Science B.V. Keywords: Plasmodium falciparum; Surface antigens; var gene transcription; Placental malaria; Field isolates 1. Introduction The display of variable adhesion antigens at the surface of the Plasmodium falciparum infected erythrocyte (IE) is a characteristic feature of erythrocytes infected by mature blood stages and it is critical for the survival and trans- mission of the parasite. In persistent infections the parasite evades the mounting immune response by antigenic vari- ation leading to characteristic waves of parasitemia [1,2]. Abbreviations: DBL, duffy-binding like; PfEMP1, Plasmodium falci- parum erythrocyte membrane protein 1; IE, infected erythrocyte; RT-PCR, reverse transcriptase polymerase chain reaction  Note: Nucleotide sequence data are available in the GenBank TM , EMBL and DDBJ databases under accession numbers AF528110- AF528155 and AF528100-AF528109. ∗ Corresponding author. Tel.: +46-8-457-10; fax: +46-8-310-525. E-mail address: mats.wahlgren@smi.ki.se (M. Wahlgren). 1 Present address: Canadian Science Center for Human and Animal Health, Special Pathogens Program, 1015 Arlington Street, Winnipeg, Manitoba, Canada R3E3R2. P. falciparum erythrocyte membrane protein 1 (PfEMP1) is the most prominent of the variable antigens exported to the erythrocyte surface. It mediates the sequestration of IE in the micro-vasculature of the brain, the placenta and other organs by adhering to host receptors on the endothelium (cy- toadhesion) and on uninfected erythrocytes (rosetting). Sex- ual forms (gametocytes) also express PfEMP1 in the early, sequestering stages but not in the later circulating forms [3]. PfEMP1 proteins are encoded by a large and diverse family of var genes, which typically consist of a highly variable 5 ′ exon encoding the extracellular domain, a rel- atively conserved intron and a conserved 3 ′ exon encoding an internally located acidic terminal segment [4]. It has previously been suggested that each parasite contains ap- proximately 50 var genes per haploid genome [5–8,18], an estimate recently confirmed with the elucidation of the genome sequence of 3D7 parasites revealing 59 var genes each encoding a unique PfEMP1. Additionally, 3D7 para- sites contain several pseudo- and truncated var genes [9]. 0166-6851/03/$ – see front matter © 2003 Published by Elsevier Science B.V. doi:10.1016/S0166-6851(03)00004-5