Non-coding, regulatory mutations play an important role in morphological evolution and contribute disproportionately to human disease phenotypes. But while important, the consequences of regulatory mutations can be difficult to predict on the basis of sequence information alone. One challenge is that regulatory DNA is highly degenerate. Equally important, however, is the fact that regulatory mutations occur within the context of complex regulatory interactions (e.g. between transcription factors and regulatory DNA) that can serve to either buffer or to enhance the impact of individual mutations.
The gene regulatory network (GRN) underlying the specification of the embryonic endomesoderm and the development of the larval skeleton in sea urchins remains one of the best annotated networks in any organism and will be used as the primary model system for a project that combines wet lab experiments (primarily single-cell sequencing) and computational analyses to understand regulatory evolution. In Berlin, the student will work with the Garfield lab to collect single-cell RNA-Seq and ATAC-Seq data from embryos generated by crossing divergent sea urchin species. The student will then work with our North Carolina based collaborators to analyze the data to address three core questions: 1) What is the relationship between changes in DNA sequence, regulatory site usage, and transcription in this developmental system? 2) Do we see evidence for tissue-specific effects in for the mutations that distinguish the two species? 3) Is there evidence for cis-regulatory changes affecting not only mean transcript abundance/chromatin accessibility, but also differences in variability or noise between species?