Duplicate Divergence in three Dimensions

Changes to the genetic make-up of species over time, known as evolution, is the fundamental process that have created the fascinating adaptations and diverse life forms populating our planet. One particularly spectacular type of genetic change, genome duplication, can arise from errors during cell division, and results in organisms with a double set of genetic material. Having such genetic redundancy increases the long-term potential for biological innovations and the emergence of new life forms. This redundancy allows nature to ‘test out’ new genetic variations while keeping a ‘backup copy’ of the original gene function. However, as doubling the genetic material often results in faulty cellular functions, genome duplications also come with short-term costs that must be overcome for survival and success. Intriguinging recent research have suggested that adaptations to overcome these challenges with having a duplicated genome could be linked to changes in the cells three-dimensional organization of DNA molecules within the nucleus. In the ThreeD project, we thus aim to explore this emerging hypothesis by tracing the changes in three dimentional genome organization and gene expression over 100 million years of evolution following a genome duplication in the ancestor of all salmonid fish.

Whole genome duplication (WGD) through autopolyploidization has played a central role in the evolution of vertebrates. In the long-term, such events increase the potential for evolutionary innovations. However, WGDs also brings significant short term evolutionary costs. In line with this, our research and that of other’s have demonstrated that WGD spark strong selection pressure on the function and regulation of many genes and pathways. How these gene regulatory adaptations are realized mechanistically is yet a standing knowledge gap, but recent studies, including preliminary data from our lab, propose that evolution at the level of 3D genome organization could be important. In the ThreeD project we therefore aim to use salmonid fish as a model to explore the emerging hypothesis that selection on 3D genome organization drives gene regulatory evolution following WGD. We will first characterize the evolution of the 3D genome structure following 100 million years of evolution after the WGD in the family of salmonid fish in three tissues and across single cell types (objective 1). We will do this by generating Hi-C data from three tissues across 6 species and characterize shared and lineage specific changes in 3D genome organization using a phylogenetic comparative approach. In addition, we will generate single-cell Hi-C from gills of Atlantic salmon to uncover cell-type specific evolution of 3D organization following WGD. Secondly, we will study the role of CTCF binding site evolution in shaping the evolution of 3D genome organization following WGD (objective 2). This is done generating CTCF ChIP-seq and analyse conservation and divergence of CTCF binding sites using a phylogenetic comparative framework like the Hi-C data. Finally, we will test if gene expression evolution, including signatures of adaptive gene duplicate divergence, is associated with evolution of 3D genome organization after WGD at both tissue and single cell type levels (objective 3).