Our recent paper on deletion polymorphism in the eve stripe 3+7 enhancer was covered by the Global medical discovery website.

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.

The charr group had one paper accepted in BMC EvoDevo last week. The title is:

Ehsan P Ahi, Kalina H Kapralova, Arnar Palsson, Valerie H Maier, Johannes Gudbrandsson, Sigurdur S Snorrason, Zophonias O Jonsson and Sigridur R Franzdottir Transcriptional dynamics of a conserved gene expression network associated with benthic-limnetic craniofacial divergence in Arctic charr. Abstract to follow.

A review article in Icelandic about the interface of development and evolution, published in the Icelandic Naturalist (Natturufraedingurinn).

Book review about, the translation of Chance and necessity by Jacques Monod, published in the Icelandic Naturalist (Natturufraedingurinn).

Our manuscript on deletion variations in regulatory elements was published in Plos One.

Naturally occurring deletions of Hunchback binding sites in the even-skipped stripe 3+7 enhancer

Arnar Palsson, Natalia Wesolowska, Sigrún Reynisdóttir, Michael Z. Ludwig and Martin Kreitman

Faculty of Life and Environmental Sciences, University of Iceland, Reykjavik, Iceland.

Institute of Biology, University of Iceland, Reykjavik, Iceland

Department of Ecology and Evolution, University of Chicago, Chicago, IL, USA.

Changes in regulatory DNA contribute to phenotypic differences within and between taxa. Comparative studies show that many transcription factor binding sites (TFBS) are conserved between species and functional studies reveal that some mutations segregating within species alter TFBS function. Single base and insertions/deletion polymorphism are rare in characterized regulatory elements in Drosophila melanogaster. Experimentally defined TFBS are nearly devoid of segregating mutations and evolutionarily conserved. For instance, 8 of 11 Hunchback binding sites in the stripe 3+7 enhancer of even-skipped are conserved between D. melanogaster and Drosophila virilis. Oddly, we found a 72 bp deletion that removes one of those binding sites (Hb8), segregating within D. melanogaster. Furthermore, a 45 bp deletion polymorphism in the spacer between the stripe 3+7 and stripe 2 enhancers, removes another predicted Hunchback site. These two deletions are separated by ~250 bp, sit on distinct haplotypes, and segregate at appreciable frequency. The Hb8del is at 5 to 35% frequency in the new world, but also has cosmopolitan distribution. There is depletion of sequence variation on the Hb8del carrying haplotype. Quantitative genetic tests indicate that Hb8del affects developmental time, but not viability of offspring. The Eve expression pattern differs between inbred lines, but the stripe 3 and 7 boundaries are seemingly not affected by the Hb8del. The deletions of those two Hb binding sites in the eve regulatory elements do not appear to be deleterious to D. melanogaster. The data reveal segregating variation for a characterized TFBS, which may reflect evolutionary turnover due to drift or co-evolution.

Figure 1 of the manuscript illustrates the main findings.