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Research

Peter Refsing Andersen - Laboratory on Genetic Innovation

Research

Fundamental processes in genome biology, such as genome stability, transcriptional regulation, and chromosome transmission are ancient and highly conserved processes. However, some genes that support these processes are remarkably young and rapidly evolving.

Our lab aims to understand the evolutionary mystery of how such highly conserved genome processes can be supported by young and often fast-evolving genes and to reveal the evolutionary drivers and consequences of this enigmatic genetic innovation. We do so by developing research projects within three connected areas that each address a key aspect of genetic innovation of genome regulation: molecular mechanisms, novel regulatory pathways, and molecular evolution.

1)       Molecular mechanisms of active heterochromatin

We recently uncovered the existence of a heterochromatin-dependent transcription mechanism underlying small RNA-mediated genome defense in the germline of the animal model system Drosophila melanogaster (Andersen et al., Nature 2017). This type of transcription differs substantially from our textbook understanding of how transcription normally works and it therefore both raises new mechanistic questions about the function of heterochromatin and provides a unique system to investigate this biology. We believe a deeper understanding of such unorthodox gene expression mechanisms will give important new insight into heterochromatin biology, into how textbook rules of gene expression are bent, and how those ‘rules’ are established in the first place.

2)      Novel genome regulatory pathways based on gene duplicates

Many genomes, including the human, harbors lots of gene duplications, but most of these are annotated as pseudogenes and are therefore often presumed to have no biological function. While this is likely true for most of the gene duplicates our recent findings of germline-expressed gene duplicates involved in genome defense (Andersen et al., Nature 2017; ElMaghraby & Andersen et al., Cell 2019) indicates that certain families of gene duplicates are likely to have obtained novel biologically important functions since the duplication event. To gain new insight into the foundation of germline genome regulation, we therefore aim to uncover the function of such young gene duplicates in this biological context.

3)      Molecular evolution of germline genome regulators

Several genes supporting germline genome regulation, including small RNA-mediated genome defense, show signatures of surprisingly rapid evolution. Such rapid evolution indicates a counter-intuitive evolutionary drive to innovate essential mechanisms. Such potential adaptive evolution could be driven either by changes in the external environment or by changes in the internal environment of the genome, such as genetic conflicts. Using Drosophila genetics and novel molecular screening technologies, we aim to uncover the drivers and functional consequences of rapid evolution in essential genome regulators.

Current projects

We are currently developing several projects within the main research areas. If you are interested in learning more, then simply get in contact to hear about the opportunities in the lab. New and independent project ideas that fit the overall lab profile are also warmly welcomed and can be further developed in collaboration.

Methods

Leveraging the powerful genetics of live fruit flies (Drosophila) we are able to connect molecular mechanisms to real biological phenotypes in germline development and fertility. We complement in vivo studies with experiments in cell culture systems to uncover further molecular mechanisms and enable reductionist approaches to our questions.

To characterize our genetic systems, we perform a range of molecular and biochemical techniques including a variety of high-throughput sequencing methods, protein interaction assays and molecular imaging techniques.

While we are currently expanding with new methods and approached, taking a look at these two recent publications (Andersen et al., Nature 2017; ElMaghraby & Andersen et al., Cell 2019) will give an idea of some key tools and approaches we apply to answer our research questions.