Predicting evolutionary targets and parameters of gene deletion from expression data

Gene deletion is traditionally thought of as a nonadaptive process that removes functional redundancy from genomes, such that it generally receives less attention than duplication in evolutionary turnover studies. Yet, mounting evidence suggests that deletion may promote adaptation via the "less-is-more" evolutionary hypothesis, as it often targets genes harboring unique sequences, expression profiles, and molecular functions. Hence, predicting the relative prevalence of redundant and unique functions among genes targeted by deletion, as well as the parameters underlying their evolution, can shed light on the role of gene deletion in adaptation.

Here, we present CLOUDe, a suite of machine learning methods for predicting evolutionary targets of gene deletion events from expression data. Specifically, CLOUDe models expression evolution as an Ornstein-Uhlenbeck process, and uses multi-layer neural network, extreme gradient boosting, random forest, and support vector machine architectures to predict whether deleted genes are "redundant" or "unique", as well as several parameters underlying their evolution. We show that CLOUDe boasts high power and accuracy in differentiating between classes, and high accuracy and precision in estimating evolutionary parameters, with optimal performance achieved by its neural network architecture. Application of CLOUDe to empirical data from Drosophila suggests that deletion primarily targets genes with unique functions, with further analysis showing these functions to be enriched for protein deubiquitination. Thus, CLOUDe represents a key advance in learning about the role of gene deletion in functional evolution and adaptation.

CLOUDe is freely available on GitHub (https://github.com/anddssan/CLOUDe).