Differential effect of evolved and ancestral viruses on the overall pattern of host gene expression Next, we sought to unravel what component of the plant gene interaction networks and metabolic pathways have been targeted by the virus during its adaptation to A. thaliana Ler. Our goal is not to identify single genes but rather global transcriptomic changes. Long-oligonucleotide microarrays representing almost all genes in A. thaliana genome have been used to this end. Five replicates were analyzed per experimental treatment (control mock-inoculated plants, and plants infected with TEV and TEV-At17) using a global reference experimental design. After quality analysis, a total of 13,722 spots, corresponding to 12,180 genes, were considered as valid for further analyses (Table S1 ). Data were normalized to the median expression of non-infected plants, and thus they reflect biological differences in gene expression in each sample analyzed. Statistical analysis allowed identification of genes whose expression responded differentially upon infection with either TEV or TEV-At17 ( Figure 2 ). When comparing global patterns of gene expression in plants infected with ancestral and adapted viruses, 496 genes showed higher expression and 1,322 genes lower expression in TEV-At17 infections than in TEV infections ( Figure 2 and Tables S2 and S3); which represents 2.7 times more down-regulated than up-regulated genes (Binomial test, P,0.0001).