Evolutionarily conserved regions in non-coding sequences represent a potentially rich source for the discovery of gene regulatory regions. While functional elements are subject to stabilizing selection, the adjacent non-functional DNA evolves much faster. Therefore, blocks of conservation, so-called phylogenetic footprints, can be detected in orthologous non-coding sequences with low overall similarity by comparative genomics [39]. Alignment algorithms, including DIALIGN, were advocated for this task. As the example in the previous section shows, however, anchoring the alignments becomes a necessity in applications to large genomic regions and clusters of paralogous genes. While interspersed repeats are normally removed ("masked") using e.g. RepeatMasker, they need to be taken into account in the context of phylogenetic footprinting: if a sequence motif is conserved hundreds of millions of years it may well have become a regulatory region even if it is (similar to) a repetitive sequence in some of the organisms under consideration [40].