Transgene silencing by the host genome defense: implications for the evolution of epigenetic control mechanisms in plants and vertebrates

Increasing evidence supports the idea that various transgene silencing phen omena reflect the activity of diverse host defense responses that act ordin arily on natural foreign or parasitic sequences such as transposable elemen ts, viroids, RNA and DNA viruses, and bacterial DNA. Transgenes or their tr anscripts can resemble these cellular invaders in a number of ways, thus ma king them targets of host protective reactions. At least two distinct host defense systems operate to silence transgenes. One acts at the genome level and is associated with de novo DNA methylation. A second line of defense o perates post-transcriptionally and involves sequence-specific RNA degradati on in the cytoplasm. Transgenes that are silenced as a consequence of the g enome defense are revealing that de novo methylation can be cued by DNA-DNA or RNA-DNA interactions. These methylation signals can be interpreted in t he context of transposable elements or their transcripts. During evolution, as transposable elements accumulated in plant and vertebrate genomes and a s they invaded flanking regions of genes, the genome defense was possibly r ecruited to establish global epigenetic mechanisms to regulate gene express ion. Transposons integrated into promoters of host genes could conceivably change expression patterns and attract methylation, thus imposing on endoge nous genes the type of epigenetic regulation associated with the genome def ense. This recruitment process might have been particularly effective in th e polyploid genomes of plants and early vertebrates. Duplication of the ent ire genome in polyploids buffers against insertional mutagenesis by transpo sable elements and permits their infiltration into individual copies of dup licated genes.