Diversification of TF Paralogs Figure 6. Functional coherence versus binding site motif similarity between TF paralogs. (a) The 95 paralogous TF pairs are sorted in decreasing order of DNA binding site motif similarity. Resulting values are normalized by subtracting the median value and dividing by the median absolute deviation. The normalized number of shared GO categories and the total number of GO categories are color coded. The corresponding figure legend indicates the normalized values. (b) The trend of normalized shared GO categories of paralogous TF pairs using a cubic smoothing spline with 4 degrees of freedom. Paralogs with high binding similarity tend to have more functions in common Kendall tau Correlation = 0.165, p- value = 0.02. doi:10.1371/journal.pone.0002345.g006 families, matched for family size of the actual dataset. Using the Mann-Whitney one-sided test we compared the R values of the foreground set with the random set given the hypothesis that the R values in the foreground set are less than or equal to the R values in the random set. For the families constructed using clustering methods, the hypothesis was rejected with a p- value = 6.84e-10. In the case of the families constructed using KOG data, the hypothesis was not rejected when all families were used. However some of the families are very large (up to 16 members) and exclusion of large families yields significant results. For instance, when we only include families of size 3 and 4, the hypothesis is rejected with a p-value = 1.3e-9. This result PLoS ONE | www.plosone.org 7 June 2008 | Volume 3 | Issue 6 | e2345