The fate of redundant genes resulting from genome duplication is poorly understood. Previous studies indicated that ribosomal RNA genes from one parental origin are epigenetically silenced during interspecific hybridization or polyploidization. Regulatory mechanisms for protein-coding genes in polyploid genomes are unknown, partly because of difficulty in studying expression patterns of homologous genes. Here we apply amplified fragment length polymorphism (AFLP)-cDNA display to perform a genome-wide screen for orthologous genes silenced in Arabidopsis suecica, an allotetraploid derived from Arabidopsis thaliana and Cardaminopsis arenosa. We identified ten genes that are silenced from either A. thaliana or C. arenosa origin in A. suecica and located in four of the five A. thaliana chromosomes. These genes represent a variety of RNA and predicted proteins including four transcription factors such as TCP3. The silenced genes in the vicinity of TCP3 are hypermethylated and reactivated by blocking DNA methylation, suggesting epigenetic regulation is involved in the expression of orthologous genes in polyploid genomes. Compared with classic genetic mutations, epigenetic regulation may be advantageous for selection and adaptation of polyploid species during evolution and development.genome duplication ͉ epigenetics ͉ gene silencing ͉ evolution P olyploidy results from duplication of a whole genome (autopolyploid) or from combining two or more distinct but related genomes (allopolyploid). It occurs in many organisms, but predominantly in vertebrates and plants (1, 2), and estimates indicate that over 70% of flowering plants had at least one event of polyploidization in their evolutionary lineage (1, 3-7). Many important crops, including banana, canola, coffee, cotton, maize, potato, oat, soybean, sugarcane, and wheat, are polyploid (8). The common occurrence of polyploids in nature probably reflects an evolutionary advantage of having redundant genes, freeing some gene copies from certain constraints of natural selection, to allow accumulation of new mutations that improve fitness. Consistent with this notion, polyploid plants are more widely distributed over more habitats than their diploid progenitors (1).The most common form of polyploids is allopolyploidy, in which two or more different but related (homoeologous) genomes are brought together in a single-cell nucleus. It is unclear how the expression of homologous genes is regulated in the hybrid cell. The vast majority of genes retain their function during evolution (7, 9-12), whereas some duplicate genes are mutated or silenced within a few million years (13). However, ''genomic shock'' as predicted by McClintock (14) occurs rapidly, resulting in sequence elimination and rearrangement (15, 16), demethylation of retroelements (17, 18), and relaxation of imprinting genes (19) in polyploid genomes. Furthermore, in interspecific hybrids or allopolyploids of vertebrates, invertebrates, and plants, one parental set of rRNA genes is subjected to silencing (20,21). The ge...