Palsson A, Wesolowska N, Reynisdóttir S, Ludwig MZ, Kreitman M (2014) Naturally Occurring Deletions of Hunchback Binding Sites in the Even-Skipped Stripe 3+7 Enhancer. PLoS ONE 9(5): e91924. doi:10.1371/journal.pone.0091924
Transcription factors (TF) bind to specific DNA sequence to regulate expression of genes. Evolutionary studies of enhancers show that some TF binding sites are well conserved while others are less constrained. The regulatory elements of the even-skipped (eve) gene in Drosophila are a textbook example of regulatory function, as specific activating and repressing TFs bind to specific binding sites and control the spatio-temporal expression of the gene. These enhancers are also a textbook example of TF binding site “turn-over” and compensatory evolution within regulatory elements.
In this study we examine natural sequence polymorphism in characterized enhancers in Drosophila melanogaster, and find the TF binding sites to be preserved by selection. Curiously we find two exceptions, both in the same enhancer of eve (that forms stripes 3 and 7 in the embryo). Both mutations are large deletions (larger than 45 bp) and both remove conserved binding sites for the same transcription factor. Hunchback is an important developmental regulator that affects expression of eve in the embryo. Both deletions are at high frequency in fly populations, and thus do not seem to be harmful for the flies. By analogy one might say that a tree is struck twice by lighting, but doesnt catch fire.
The most puzzling result of this study is that both Hb binding sites are conserved and the two deletions removing them are at up to 35% frequency in the population.
Furthermore, one of the Hb sites was not noticed earlier, because the Drosophila reference genome is homozygous for the deletion allele.
We postulate that coevolution between Hb function and its target sequences best explains the data. In other words, this could reflect compensatory evolution of cis and trans factors, that is developmental system drift in the gene regulatory network controlling stripe formation in fruitfly embryos.