title: Controlling for Phylogenetic Relatedness and Evolutionary Rates Improves the Discovery of Associations Between Species' Phenotypic and Genomic Differences.
abstract: The growing number of sequenced genomes allows us now to address a key question in genetics and evolutionary biology: which genomic changes underlie particular phenotypic changes between species? Previously, we developed a computational framework called Forward Genomics that associates phenotypic to genomic differences by focusing on phenotypes that are independently lost in different lineages. However, our previous implementation had three main limitations. Here, we present two new Forward Genomics methods that overcome these limitations by (1) directly controlling for phylogenetic relatedness, (2) controlling for differences in evolutionary rates, and (3) computing a statistical significance. We demonstrate on large-scale simulated data and on real data that both new methods substantially improve the sensitivity to detect associations between phenotypic and genomic differences. We applied these new methods to detect genomic differences involved in the loss of vision in the blind mole rat and the cape golden mole, two independent subterranean mammals. Forward Genomics identified several genes that are enriched in functions related to eye development and the perception of light, as well as genes involved in the circadian rhythm. These new Forward Genomics methods represent a significant advance in our ability to discover the genomic basis underlying phenotypic differences between species. Source code: https://github.com/hillerlab/ForwardGenomics/.
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
authors.forename: Xavier
authors.initials: X
authors.lastname: Prudent
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
authors.forename: Genis
authors.initials: G
authors.lastname: Parra
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Schwede
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Max Planck Institute for the Physics of Complex Systems, Dresden, Germany.
authors.forename: Juliana G
authors.initials: JG
authors.lastname: Roscito
authors.affiliation: Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany Max Planck Institute for the Physics of Complex Systems, Dresden, Germany hiller@mpi-cbg.de.
authors.forename: Michael
authors.initials: M
authors.lastname: Hiller
mesh_terms: D000818:Animals; D001483:Base Sequence; D005075:Biological Evolution; D019295:Computational Biology / Q000379:methods*; D003198:Computer Simulation; D019143:Evolution, Molecular; D049810:Genetic Speciation; D023281:Genomics / Q000379:methods*; D005838:Genotype; D008957:Models, Genetic; D059645:Mutation Rate; D010641:Phenotype; D010802:Phylogeny
keywords: evolutionary and comparative genomics; gene loss.; phenotype–genotype associations