Project description
How do 3D regulatory landscapes shape the evolution of sex determination?
All cells of a living organism inherit a complete genome, containing a full set of genes. However, cells will only use those genes that are relevant to reach their differentiated status and to form associated tissues. When, where and how much genes are expressed is controlled by 3D regulatory landscapes, resulting from an interplay between genes, regulatory elements and 3D chromatin organisation. To date, how 3D regulatory landscapes influence the evolution of developmental programs is still largely unexplored. Harnessing recent technological advances, the EU-funded project 3D-REVOLUTION will investigate this aspect, using gonadal sex determination in tetrapods as a model.
Objective
Vertebrate genomes are organized in 3D regulatory landscapes that control pleiotropic gene expression. Within them, transcription emerges from a precise interplay between genes, regulatory elements and 3D chromatin organization. We and others have shown how mutations in these regulatory layers can modulate phenotypes. However, how 3D regulatory landscapes shape the evolutionary history of developmental programs is still largely unexplored.
Our limited capability to read, interpret and modify genomes has constrained our knowledge on how gene regulation evolves. However, recent advances in long-range sequencing, single-cell, chromatin interaction and genome editing methods offer novel tools to link genomic variation and phenotypes. Here, I will combine these methods to investigate how changes in 3D regulatory landscapes contribute to refine the function of developmental programs. As a testbed, I will study gonadal sex determination, an essential process for species perpetuation but characterized by a remarkable evolutionary plasticity.
We will use single-cell transcriptomics across tetrapod clades to unravel the core and variable transcriptional network of sex determination. Single-cell epigenomics and novel chromatin interaction methods will reconstruct 3D regulatory landscapes and infer sources of regulatory variation. With phylogenomic comparative strategies, we will estimate the contribution of different types of mutations to different sex determination programmes, as well as the impact of whole genome duplications. Finally, we will develop innovative transgenic methods for inter-species replacement of 3D regulatory landscapes, using this technology to activate early estrogen synthesis in mouse.
3D-REVOLUTION will provide ground-breaking insights on the evolution of gene regulation. This will improve our understanding of the genomic sources and underlying mechanisms of phenotypical variation, which are relevant for developmental and evolutionary genetics.
Fields of science
Keywords
Programme(s)
- HORIZON.1.1 - European Research Council (ERC) Main Programme
Funding Scheme
HORIZON-ERC - HORIZON ERC GrantsHost institution
28006 Madrid
Spain