Animal complexity defines the functionality of synonymous mutations through mediating microRNA regulations

Abstract

Most recently, Shen et al. revealed that most synonymous mutations (SMs) in yeast genes are strongly non-neutral, however, which was soon challenged by Kruglyak et al. who find no evidence for deleterious effect on fitness of SMs in yeast genes. We previously revealed that SMs in numerous human genes show functionality through changing miRNA regulations. Given that higher animals show higher complexity of miRNA regulations, here we present a hypothesis that SMs in lower animal genes show less functionality and vice versa. To confirm this, we comprehensively investigated the SMs changing miRNA regulations in yeast, C.elegans, Drosophila, mouse, and human. As expected, the result showed that the proportion of SMs affecting gene functionality through altering miRNA regulations is about 0%, 14%, 16%, 51%, and 60% in yeast, C. elegans, Drosophila, mouse, and human, respectively, suggesting that the complexity of animals indeed determines the functionality of SMs through mediating miRNA regulations. Finally, this study supports no evidence that most SMs in yeast genes are deleterious.