Talk title: Regulatory evolution of mammalian genomes
Time: Wed 24th October, 12:15-13:00
Tissues and cell types have largely conserved gene expression programs across mammals, enabling extrapolation from animal studies to human medical conditions. These gene expression patterns are controlled by collections of regulatory elements combining promoters and tissue-specific enhancers. However, it is now well-documented that regulatory elements have experienced extensive divergence and turn-over during mammalian evolution. How stable gene expression is maintained by rapidly evolving regulatory landscapes remains a fundamental question in evolutionary genetics, as well as a crucial prior to the use of animal models for human functional genetics.
We report here on an in-depth analysis of gene expression and regulation across mammalian evolution. Using liver as a representative organ, we profiled gene expression as well as histone marks typical of active promoters and enhancers in 20 different mammals. We used this data to quantify how promoters and enhancers evolve in mammals, and how this evolution affects gene expression downstream. This analysis revealed a complex relationship between gene expression and regulatory evolution. First, we show that promoters and enhancers are under significantly different evolutionary pressures: promoters remain largely active across mammals while enhancers are much more evolutionarily labile. Second, regulatory elements exhibit a broad range of evolutionary plasticity from those active across most mammals to those found in only one or a few species. We show how these degrees of conservation translate in terms of local gene functions, gene expression levels, and gene expression stability. Importantly, we report that highly expressed and stable genes are associated with complex arrays of promoters and enhancers, which can exhibit significant turnover across species as long as the overall landscape complexity is maintained. Our results underscore how functional redundancy in regulatory programs allows for resilience at the gene expression level in mammalian genomes.