Diversification of TF Paralogs Figure 5. Expression of 95 pairs of TF paralogs in 23 non-redundant human tissues. (a) Columns correspond to the tissues and the rows correspond to the TF pairs. Rows are ordered in decreasing order of DNA binding similarity of TF pairs. The expression value for each TF is normalized in a tissue-specific way. The color of each cell represents the normalized expression level in each tissue for each TF in the pair. Grey cells indicate that the level of expression for this tissue was below our threshold for noise and hence, effectively zero. The thresholds are based on three equal splits of the range of expression values in a tissue-specific fashion. (b) Trend plot of the number of tissues where both TFs in a pair are highly expressed versus the DNA binding motif similarity score for the TF pair, using a cubic smoothing spline with 5 degrees of freedom. The (RXRB-RXRB) pair in fact corresponds to two distinct (partially overlapping) Ensembl genes. See Data file 2 for Ensembl gene ids. doi:10.1371/journal.pone.0002345.g005 the gene with the most similar DNA binding site motif. Therefore, a ratio of R = 1 would indicate that the highest expressed gene in a family for a given tissue has most diverged in expression from the gene with which it shares the most binding similarity. In order to reduce the chances of considering irrelevant tissues (where all family members are expressed at low level), we only considered the tissues in which the maximum expression among the family members was greater than the median expression of all TF genes in that tissue. We then compared the R values computed from our dataset with that for 10000 random groupings of the TF genes in PLoS ONE | www.plosone.org 6 June 2008 | Volume 3 | Issue 6 | e2345