@article {Rohlfs004374, author = {Rori V. Rohlfs and Rasmus Nielsen}, title = {Phylogenetic ANOVA: The Expression Variance and Evolution (EVE) model for quantitative trait evolution}, elocation-id = {004374}, year = {2015}, doi = {10.1101/004374}, publisher = {Cold Spring Harbor Laboratory}, abstract = {A number of methods have been developed for modeling the evolution of a quantitative trait on a phylogeny. These methods have received renewed interest in the context of genome-wide studies of gene expression, in which the expression levels of many genes can be modeled as quantitative traits. We here develop a new method for joint analyses of quantitative traits within and between-species, the Expression Variance and Evolution (EVE) model. The model parameterizes the ratio of population to evolutionary expression variance, facilitating a wide variety of analyses, including a test for lineage-specific shifts in expression level, and a phylogenetic ANOVA that can detect genes with increased or decreased ratios of expression divergence to diversity, analogous to the famous HKA test used to detect selection at the DNA level. We use simulations to explore the properties of these tests under a variety of circumstances and show that the phylogenetic ANOVA is more accurate than the standard ANOVA (no accounting for phylogeny) sometimes used in transcriptomics. We then apply the EVE model to a mammalian phylogeny of 15 species typed for expression levels in liver tissue. We identify genes with high expression divergence between-species as candidates for expression level adaptation, and genes with high expression diversity within-species as candidates for expression level conservation and/or plasticity. Using the test for lineage-specific expression shifts, we identify several candidate genes for expression level adaptation on the catarrhine and human lineages, including genes putatively related to dietary changes in humans. We compare these results to those reported previously using a model which ignores expression variance within-species, uncovering important differences in performance. We demonstrate the necessity for a phylogenetic model in comparative expression studies and show the utility of the EVE model to detect expression divergence, diversity, and branch-specific shifts.}, URL = {https://www.biorxiv.org/content/early/2015/06/02/004374}, eprint = {https://www.biorxiv.org/content/early/2015/06/02/004374.full.pdf}, journal = {bioRxiv} }