Response to Comment on “microRNAs in the Same Clusters Evolve to Coordinately Regulate Functionally Related Genes”

摘要

Metazoan miRNAs are significantly enriched in clusters. In a previous study (Wang, et al. 2016), we proposed a “functional co-adaptation” model to explain how clustering helps new miRNAs survive and develop functions during long-term evolution. Recently, Marco re-analyzed our data and came to a different conclusion. The major concern Marco raised is whether the observed number of genes targeted by at least two conserved miRNAs with different seeds from the same miRNA clusters is statistically higher than the number obtained under the assumption of randomness. Marco claimed that our approach of shuffling miRNA–target interactions would lead to spuriously low P values. Marco also argued our observation that clustered miRNAs have more common targets than expected is mostly contributed by seeds with similar sequences. However, we found his analyses were conducted in an inappropriate approach and do not refute our model. We also provide new evidences to reaffirm our model.