As I wrote about for our last paper, I hate the way scientific publishing works today, especially the insane delays (average is about 9 months) between when a lab is ready to share its work and when the work is actually available. So, from now on we are going to post all of our papers online when we feel they’re ready to share – before they go to a journal. We’ll then solicit comments from our colleagues and use them to improve the work prior to formal publication.Physicists and mathematicians have been doing this for decades, as have increasing number of biologists. It’s time for this to become standard practice.
Ground rules: I will not filter comments except to remove obvious spam. You are welcome to post comments under your name or under a pseudonym – I will not reveal anyone’s identity – but I urge you to use your real name as I think we should have fully open peer review in science. The original paper and comments will remain available here as a record of the review process.
The paper is now available at arXiv. Please use the arXiv version for formal citations.
This paper is the result of several years of work from Mathilde Paris, a very talented postdoctoral fellow in my lab. Mathilde was interested in looking at the evolution of transcription factor binding in highly diverged Drosophila species and the effect of changes in transcription factor binding on gene expression. So she carried out a series of chromatin immunoprecipitation experiments using antibodies raised against four D. melanogaster proteins involved in early anterior-posterior (head -> tail) patterning. She carried out ChIP-seq experiments in D. melanogaster as well as D. pseudoobscura (diverged ~30mya) and D. virilis (diverged ~40mya). There were a lot of technical challenges in getting these experiments to work to our satisfaction (described in the methods section of the paper), but eventually Mathilde had a dataset in which we had sufficient confidence to analyze in detail.
The most striking observation about the ChIP data is just how different the binding patterns of these factors are in these different species, which, for all intents and purposes, undergo identical early developmental processes. We can identify two clear factors driving this divergence: the gain and loss of binding sites for these two factors (for background on binding site turnover see this 2008 paper from our lab), and the gain and loss of binding sites for the early embryonic master regulator Zelda (see this 2011 paper from our lab for more information about Zelda). However, these two effects did not completely explain the observed divergence, which may also be influenced by environmental factors (the species do not all develop at the same temperatures or same rates) and developmental, biochemical and experimental noise.
In contrast to the divergence of transcription factor binding, gene expression in stage-matched embryos is highly conserved. And one of the central issues discussed in the paper is why there is this discordance between transcription factor binding and gene expression divergence.
As always, we await your comments, and will respond as quickly as we can.