AbstractWhen a dispensable gene is duplicated (ancestral dispensability), genetic buffering and duplicate compensation together maintain the gene dispensability, whereas duplicate compensation is the only mechanism when an essential gene is duplicated (ancestral essentiality). To explore the distinct pattern of genetic robustness between these evolutionary scenarios, we formulated a probabilistic model with some biologically reasonable assumptions for analyzing a set of duplicate pairs with three possible states: double-dispensable (DD), semi-dispensable (one dispensable one essential, DE) or double-essential (EE). A computational pipeline is then developed to predict the distribution of three states (DD, DE and EE) conditional of ancestral dispensability or essentiality, respectively. This model was applied to yeast duplicate pairs from a whole-genome duplication, revealing that the process of essentiality of those duplicated from essential genes could be significantly higher than that of those duplicated from dispensable genes. We thus proposed a hypothesis that the process of sub-functionalization may be faster than neo-functionalization. Our analysis may provide some new insights about the role of duplicate compensation on genetic robustness.