a The activity of a given target can be evaluated in the presence of a cognate miRNA. ‘Switch’ targets are essentially inactive following miRNA-mediated repression, whereas ‘tuning’ targets produce functional protein in the domain of miRNA activity. Both of these terms apply to evolutionarily conserved target relationships. Non-conserved but functional sites may mediate repression that is incidental or otherwise compensated for by other regulatory mechanisms; these are termed ‘neutral’ targets. Non-conserved sites may occasionally mediate beneficial, species-specific regulation. Not shown are ‘anti-targets’, transcripts for which miRNA-mediated repression is deterimental, such that the acquistion of target sites is avoided. b Another means of classification is to evaluate whether loss of function of a specific miRNA is associated with a phenotype, or whether the removal of target sites from a specific target causes a phenotype. For many conserved miRNAs and their conserved targets, the repression is likely to be beneficial enough to be selected during evolution but, overall, to be auxiliary to other means of gene regulation. Only a subset of miRNAs, with a small number of targets, mediate regulation with genetically defined consequences; we call these ‘miRNA genetic switches’, c One may consider the total number of targets whose repression by a miRNA in a given setting can be detected by quantitative means. Alternatively, a more stringent classification would be to consider only those targets whose repression by a miRNA is of detectable phenotypic consequence.