Fig. 8.

Comparison of the functional impact of human miRNAs in evolutionarily related families and singleton miRNAs. Human miRNAs in families of evolutionarily related miRNAs have a greater functional impact—as measured by breadth of expression, number of gene targets, and disease associations—than singleton miRNAs; however, this is largely due to their greater age. (a) Compared to human miRNA singletons, miRNAs in families of evolutionarily related miRNAs are expressed in more tissues (P = 1.8e–03; Mann-Whitney U test). (b) Human miRNAs in families target significantly more genes than singleton miRNAs (P = 3.8e–15). (c) Human miRNAs in families are associated with significantly more diseases than singleton miRNAs (P = 2.1e–28). (d-f) The differences between family and singleton miRNA are attenuated and less consistent when miRNAs are stratified by age (P = 0.067, 7.4e–05, and 1.5e–04, respectively; stratified Mann-Whitney U test). This suggests that differences in the age distribution of family vs. singleton miRNA likely contribute to their different functional impact