Genomes in Evolution – How Bats learned to fly
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 wings in bats. In a preliminary study, we generated a full chromosome genome of the short tailed fruit bat (Carollia perspicillata). Furthermore, we collected fore- and hindlimbs from bat embryos (Carollia perspicillata), covering limb development from the early limb bud to the later stages of skeletal growth. Using these tissues, we produced ChIP-seq and ATAC-seq data and generated a genome-wide map of enhancers. In addition, we generated single-cell RNA-seq (sc-RNA-seq) as well as sc-ATAC-seq data from these tissues. An equivalent data set was generated from mouse embryos. This unique dataset provides us with novel insights into limb development and how it can be modified to generate extreme differences in morphology. In an integrated data analysis we will identify regulated genes in Carollia limb development and changes in their corresponding regulatory landscapes. Identified regulatory regions consisting of enhancers, promoter and/or lncRNAs will be reconstituted in mice by genomic engineering. For this purpose we will synthetically produce large DNA sequences using a yeast assembly protocol and insert them into the mouse genome. Transgenic mice will be used to dissect how genomic changes translate into altered gene expression and phenotypes on cellular and regulatory level. Finally, we will create de novo designer regulatory landscapes that can be used as a testbed for experimental perturbations.
The possibility to re-engineer sequences in another species will provide us with an unprecedented insight how non-coding DNA regulates gene expression and how this translates into 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.