Mutational pleiotropy and the strength of

20 Variational modules, sets of pleiotropically covarying traits, affect phenotypic evolution, and 21 therefore are predicted to reflect functional modules, such that traits within a variational 22 module also share a common function. Such an alignment of function and pleiotropy is 23 expected to facilitate adaptation by reducing the deleterious effects of mutations, and 24 allowing coordinated evolution of functionally related sets of traits. Here, we adopt a high25 dimensional quantitative genetic approach using a large number of gene expression traits in 26 Drosophila serrata to test whether functional grouping, defined by GO terms, predicts 27 variational modules. Mutational or standing genetic covariance was significantly greater 28 than among randomly grouped sets of genes for 38% of our functional groups, indicating 29 that GO terms can predict variational modularity to some extent. We estimated stabilizing 30 selection acting on mutational covariance to test the prediction that functional pleiotropy 31 would result in reduced deleterious effects of mutations within functional modules. 32 Stabilizing selection within functional modules was weaker than that acting on randomly 33 grouped sets of genes in only 23% of functional groups indicating that functional alignment 34 can reduce deleterious effects of pleiotropic mutation, but typically does not. Our analyses 35 also revealed the presence of variational modules that spanned multiple functions. 36