Insights into gene tissue specificity and protein-protein interactions in the context of purifying selection in humans

Background: How much are natural selection and gene characteristics, such as the number of protein-protein interactions (PPIs), tissue specificity (𝞽), and expression level, connected? Methods: In order to investigate these relationships, we combined different metrics linked to genetic constraints and analyzed their distribution concerning PPIs, 𝞽 and expression levels. Results: We discovered a positive correlation between genetic constraints, PPIs, and expression levels in all tissues. On the other hand, we obtained a negative correlation between genetic constraints and 𝞽. Furthermore, the fraction of variance in PPI and 𝞽 explained by the constraints metrics is around 6% and 10%, respectively. Conclusions: We observed that the variance of expression of tissue-specific genes seems not related to their level of selection constraints, which is the opposite of what is found on non-tissue-specific genes. Overall these observations would help to elucidate the relationship between natural selection and gene features.