Functional evolution of cardiac microRNAs in heart development and functions.

MicroRNAs (miRNAs) are a class of endogenous small noncoding RNAs that regulate gene expression either by degrading target mRNAs or by suppressing protein translation. miRNAs have been found to be involved in many biological processes, such as development, differentiation, and growth. However, the evolution of miRNA regulatory functions and networks has not been well studied. In this study, we conducted a cross-species analysis to study the evolution of cardiac miRNAs and their regulatory functions and networks. We found that conserved cardiac miRNA target genes have maintained highly conserved cardiac functions. Additionally, most of cardiac miRNA target genes in human with annotations of cardiac functions evolved from the corresponding homologous targets, which are also involved in heart development-related functions. On the basis of these results, we investigated the functional evolution of cardiac miRNAs and presented a functional evolutionary map. From this map, we identified the evolutionary time at which the cardiac miRNAs became involved in heart development or function and found that the biological processes of heart development evolved earlier than those of heart functions, for example, heart contraction/relaxation or cardiac hypertrophy. Our study of the evolution of the cardiac miRNA regulatory networks revealed the emergence of new regulatory functional branches during evolution. Furthermore, we discovered that early evolved cardiac miRNA target genes tend to participate in the early stages of heart development. This study sheds light on the evolution of developmental features of genes regulated by cardiac miRNAs.