Gene expression in early Drosophila embryos is highly conserved despite extensive divergence of transcription factor binding
Mathilde Paris, Tommy Kaplan, Xiao Yong Li, Jacqueline E. Villalta, Susan E. Lott, Michael B. Eisen
(Submitted on 1 Mar 2013)

To better characterize how variation in regulatory sequences drives divergence in gene expression, we undertook a systematic study of transcription factor binding and gene expression in the blastoderm embryos of four species that sample much of the diversity in the 60 million-year old genus Drosophila: D. melanogaster, D. yakuba, D. pseudoobscura and D. virilis. We compared gene expression, as measured by mRNA-seq to the genome-wide binding of four transcription factors involved in early development, as measured by ChIP-seq (Bicoid, Giant, Hunchback and Kr\”uppel). Surprisingly, we found that mRNA levels are much better conserved than individual binding events. We looked at binding characteristics that may explain such evolutionary disparity. As expected, we found that binding divergence increases with phylogenetic distance. Interestingly, binding events in non-coding regions that were bound strongly by single factors, or bound by multiple factors, were more likely to be conserved. As this class of sites are most likely to be involved in gene regulation, the divergence of other bound regions may simply reflect their lack of function. We used a model of quantitative trait evolution to compare the changes of gene expression with nearby regulatory TF binding. We found that changes in gene expression were poorly explained by changes in associated TF binding. These results suggest that some of the differences in sequence and binding have limited effect on gene expression or act in a compensatory manner to maintain the overall expression levels of regulated genes.