Until recently, large-scale population genomics studies of metazoan TFBSs were unthinkable because of the limited number of available genotypes and global TF binding profiles. However, advances in sequencing technology have paved the way for high-throughput efforts, such as the human 1000 Genomes project [21] and Drosophila Genetic Reference Panel (DGRP) [22], that are making available an increasing number of individual genomes originating from the same population. Combining these data with the binding maps of dozens of TFs in both species generated by the Encyclopedia of DNA Elements (ENCODE) for human [23], and modENCODE and other published sources in Drosophila [2,24-30] has provided an unprecedented resource for analyzing TFBS functional constraints.
