Prof. Scott V. Edwards, Harvard University

Title:
PhyloG2P: the new science of connecting genomes to phenotypes via phylogenies

Abstract:
‘PhyloG2P’ is a monicer for the paradigm in evolutionary genmics of linking genomic variation to phenotypes using phylogenetic trees. PhyloG2P methods capitalize on different genomic signatures – presence/absence of genes, loss of function of genes, insertions and deletions, and shifting evolutionary rates – to find the genomic drivers of phenotypic change on clades that are not amenable to classical genetic approaches.  In this talk I will present details of the PhyloAcc (‘Phylo-A-see-see’) family of Bayesian approaches to PhyloG2P and their application to diverse phenotypic traits in birds and mammals. PhyloAcc methods focus on associating changes in evolutionary rates of putative noncoding regulatory regions, such as conserved non-exonic elements (CNEEs), to changes in a binary or continuous trait. The basic PhyloAcc model finds CNEEs undergoing acceleration in concert with a change in a binary trait, such as convergent losses of flight in birds. We have used this approach on genome-wide CNEEs to find conserved enhancers that accelerated convergently in flightless birds (Paleognaths). We have further cataloged regions of open chromatin and applied massively parallel reporter assays (MPRAs) to demonstrate changes in function of enhancers undergiong acceleration. We have also recently produced additional variants of PhyloAcc that incorporate increased biological realism and analysis of continuous phenotypic traits, such as maximum longevity in mammals. PhyloG2P methods provide powerful insights into genome-phenome connections in otherwise genetically intractable lineages and help determine the relative contributions of protein and regulatory evolution to phenotypic diversification across the Tree of Life.