Genome evolution driven by transposable elements across the Tree of Life

Genome sequences for all species are transforming biology. Comparative analysis reveals function, and understanding how genomes work is intimately entangled with understanding how they evolved. Here we will develop new methods to inform the origins and function of the human genome, combining computational software that operates at the scale of data to come, together with experimental investigation of how structural genome variation arises and is used in evolution. Although most individual mutations are single-base, more sequence is changed through structural variation, driven in large part by transposable elements (TEs), more often inducing functional consequences. We will develop novel genome alignment methods based on new fast algorithms that explicitly model TE insertions and non-allelic homologous recombination. Experiments in Drosophila will help develop the methods and provide innovative large-scale experimental evolution studies of TE dynamics and host genome response. Then we will apply these methods across all available vertebrate data, integrating with human pangenomes, with further experimental studies in two vertebrate systems where high TE activity and structural variation couple with rapid evolution and remarkable adaptations to phenotype and lifestyle. Together these will empower human biomedical genetics to gain maximally from the era of genome sequencing across the tree of life.