Mycoplasma hyorhinis vlp gene transcription: Critical role in phase variation and expression of surface lipoproteins

Mycoplasma hyorhinis contains clustered vip genes encoding variable lipoproteins (Vlps), the major coat proteins and surface antigens of this wall-less prokaryotic pathogen. vip genes are subject to discrete, high frequency mutations independently affecting the size or the expression of variant vip products. Change in vip size occurs by mutations altering the number of tandem intragenic repeats at the 3' end of each single-copy vip gene. In this report, phase-variant vip expression is shown to result from altered vip gene transcription. vlpA, vlpB and vlpC transcripts were monitored in a clonal lineage selected to display various vip phenotypes. Each vip gene was expressed as a distinct transcript, which was subject to drastic ON/OFF switches associated with random insertion/deletion mutations in a homopolymeric tract of adenine residues in the promoter region of all vip genes. Unexpectedly, the level of vip transcripts appeared to depend on the length of the corresponding genes in the ON configuration. Higher proportional levels of shorter vip transcripts were shown to reflect a greater abundance of short vip lipoproteins present in L-[S-35]-cysteine-labelled membrane protein preparations. The vip cluster provides a heritable, and highly mutable, locus for the generation of surface diversity through random promoter mutations affecting the expression of genes, whose products also vary in length and abundance, by virtue of separate mutations in structural regions of the genes.