Genomic Characterization of Variable Surface Antigens Reveals a Telomere Position Effect as a Prerequisite for RNA Interference-Mediated Silencing in Paramecium tetraurelia

Abstract

Antigenic or phenotypic variation is a widespread phenomenon of expression of variable surface protein coats on eukaryotic microbes. To clarify the mechanism behind mutually exclusive gene expression, we characterized the genetic properties of the surface antigen multigene family in the ciliate Paramecium tetraurelia and the epigenetic factors controlling expression and silencing. Genome analysis indicated that the multigene family consists of intrachromosomal and subtelomeric genes; both classes apparently derive from different gene duplication events: whole-genome and intrachromosomal duplication. Expression analysis provides evidence for telomere position effects, because only subtelomeric genes follow mutually exclusive transcription. Microarray analysis of cultures deficient in Rdr3, an RNA-dependent RNA polymerase, in comparison to serotype-pure wild-type cultures, shows cotranscription of a subset of subtelomeric genes, indicating that the telomere position effect is due to a selective occurrence of Rdr3-mediated silencing in subtelomeric regions. We present a model of surface antigen evolution by intrachromosomal gene duplication involving the maintenance of positive selection of structurally relevant regions. Further analysis of chromosome heterogeneity shows that alternative telomere addition regions clearly affect transcription of closely related genes. Consequently, chromosome fragmentation appears to be of crucial importance for surface antigen expression and evolution. Our data suggest that RNAi-mediated control of this genetic network by trans-acting RNAs allows rapid epigenetic adaptation by phenotypic variation in combination with long-term genetic adaptation by Darwinian evolution of antigen genes.

Differential expression of multidrug resistance-related proteins in adriamycin-resistant (pumc-91/ADM) and parental (pumc-91) human bladder cancer cell lines

“…In the present study, differential expression of VEGF was detected between the protein and gene level. It may be hypothesized that methylation of cytosine induced the abnormal gene expression, whereas the DNA sequence and gene product remained normal (32). Besides methylation, acetylation may regulate gene transcription, leading to differential expression between the protein and gene (33).…”

Insights into transgenerational epigenetics from studies of ciliates

“…However, this is not the case. While the old macronucleus degrades and contributes no DNA to the new macronucleus, it does influence the development of the new macronucleus through epigenetic processes like RNA-guided genome scanning (Baranasic et al, 2014; Chalker et al, 2013; Chalker and Yao, 2011; Meyer and Duharcourt, 1996; Nowacki and Landweber, 2009). It is possible, however, that only a portion of the genome is scanned (Hamilton et al, 2016; Schoeberl et al, 2012).…”

“…Serotypes, determined by the kinds of surface proteins expressed and transported to the cell surface, are also epigenetically regulated in ciliates (Baranasic et al, 2014; Lepere et al, 2008; Simon and Schmidt, 2007). The phenotypic variation created by the various surface antigens enables recognition between cells, may protect ciliates from predators, or could be a defense mechanism against biotic and abiotic factors (Preer, 1986; Simon and Kusch, 2013; Sonneborn, 1970).…”

“…The phenotypic variation created by the various surface antigens enables recognition between cells, may protect ciliates from predators, or could be a defense mechanism against biotic and abiotic factors (Preer, 1986; Simon and Kusch, 2013; Sonneborn, 1970). Over the last 70 years, studies have shown that the inheritance of surface antigen genes follows Mendelian rules; however, the expression of the antigens is epigenetically regulated (Baranasic et al, 2014; Beale, 1957; Lepere et al, 2008; Sonneborn, 1943). …”

“…Additionally, Tetrahymena thermophila uses programmed DNA rearrangements in mating type determination through karyonidal inheritance (Cervantes et al, 2013). Both scnRNAs and small interfering RNAs (siRNAs) have been implicated as possible epigenetic mechanisms for the inheritance of surface antigens (Baranasic et al, 2014; Lepere et al, 2008). Hence, the epigenetic processes described here likely reflect modification of genome defense machinery that originally evolved to silence invading transposable elements.…”