Maintenance of quantitative genetic variance in complex, multi-trait phenotypes: The contribution of rare, large effect variants in two Drosophila species

Abstract

The interaction of evolutionary processes to determine quantitative genetic variation has implications for contemporary and future phenotypic evolution, as well as for our ability to detect causal genetic variants. While theoretical studies have provided robust predictions to discriminate among competing models, empirical assessment of these has been limited. In particular, theory highlights the importance of pleiotropy in resolving observations of selection and mutation, but empirical investigations have typically been limited to few traits. Here, we applied high dimensional Bayesian Sparse Factor Genetic modelling to 3,385 gene expression traits from Drosophila melanogaster and from D. serrata to explore how genetic variance is distributed across high-dimensional phenotypic space. Surprisingly, most of the heritable trait covariation was due to few lines (genotypes) with extreme (>3 IQR from the median) values. This observation, in the two independently sampled species, suggests that the House of Cards (HoC) model might apply not only to individual expression traits, but also to emergent co-expression phenotypes. Intriguingly, while genotypes extreme for a multivariate factor also tended to have a higher proportion of individual traits that were extreme, we also observed genotypes that were outliers for multivariate factors but not for any individual traits. We observed other consistent differences between heritable multivariate factors with outlier lines versus those factors that conformed to a Gaussian distribution of genetic effects, including differences in gene functions. We use these observations to identify further data required to advance our understanding of the evolutionary dynamics and nature of standing genetic variation for quantitative traits.