Illustration of the difference between a sequence homology map and a functional homology map. (a) An ancestral promoter sequence with five functional sites. (b) Three unaligned descendent sequences derived from the ancestral promoter sequence. In the first descendent sequence, the old site a was functionally replaced by the new site a' because of evolutionary sequence changes. Similar replacement turnovers occurred at site b in the second and site c in the third descendent sequence, respectively. The three TFBS pairs a-a', b-b', and c-c' are homologous at the functional level but not at the sequence level. (c) Alignment of the three descendent sequences based on sequence base-pair homology. (d) Alignment of the three descendent sequences based on their homology at the functional level. The figure illustrates cases in which it is easier to identify functional elements a(a'), b(b'), and c(c') and to predict gene functions from the homology map at the functional level rather than at the sequence level.
Huang et al. Genome Biology 2007 8:R225 doi:10.1186/gb-2007-8-10-r225