Genomes in evolution - How the hedgehog got its spines
Prof. Dr. Stefan Mundlos
Evolutionary processes have resulted in the most diverse adaptions to environmental challenges. How such adaptations evolve and how they are encoded in the genome remains one of the great mysteries in biology. Here, we follow the hypothesis that a high degree of the morphological diversity in the animal kingdom can be attributed to changes in the regulatory genome and that these changes can be identified using recent technological advances including the generation of high-resolution genomes, epigenetic mapping of regulatory sequences and single-cell sequencing. In a previous study we successfully applied this strategy to investigate the genomic origin of intersexuality in female moles (Real et al. 2020).
Here, we want to elucidate a fascinating phenomenon in evolution, the development of spines in hedgehogs, in particular the four-toed hedgehog (Atelerix albiventris). In a preliminary study, we generated a full chromosome genome of Atelerix using a combination of long-read PacBio sequencing and HiC for contig assembly. In our first aim we will compare these genome to that of mouse and human in order to identify breaks of synteny that disrupt chromatin domains. In a second step we will search for the presence of these breaks in other hedgehog genomes and related species (mole and shrew) in order to identify hedgehog-specific rearrangements. To identify changes in regulatory landscapes, we sampled embryonic skin from Atelerix and mouse from dorsal (spines in hedgehogs) and ventral (no spines) skin at stages corresponding to placode formation, the precursor of hair/spine formation. These samples will be subjected to ChIP-seq for histone marks and ATAC-seq in order to identify active enhancers/promoters. In the next step, we will generate an expression map of mouse and Atelerix embryonic skin using bulk and single-cell RNA-seq and compare dorsal vs. ventral skin and Atelerix vs. mouse. In integrated data analysis the results from will be merged to identify regulated genes in Atelerix dorsal skin that correspond to changes in enhancer activity and/or genomic rearrangements at synteny breaks resulting in altered regulatory landscapes. Identified genes will be tested for expression by WISH in Atelerix and mouse skin samples. Identified regulatory sequences will be tested in the mouse by comparing mouse vs. hedgehog in an in vivo enhancer assay. Finally, candidate sequences that might be involved in spine development in the hedgehog will be inserted into the mouse genome to investigate their effect on gene regulation and phenotype.
M Real F, et al. The mole genome reveals regulatory rearrangements associated with adaptive intersexuality. Science. 2020 Oct 9;370(6513):208-214.
For more information have a look at the website of the Development & Disease group.