Despite the now known importance of miRNAs in the control of gene expression [67],[132], only four miRNA loci have been identified in intense genetic screens in C. elegans and Drosophila, and none in mammals. This may be partly due to the fact that C. elegans is hermaphroditic and naturally driven to homozygosity in individual isolates, without the need for laborious back-crossing, and flies are routinely bred to homozygosity in mutational screens, making screening of recessive mutations far more efficient than in mice. There was also an element of serendipity, in that the first identified miRNA locus, lin-4, expressed a small RNA whose complementary sequence was present in multiple copies in the 3′ UTR of its target gene, lin-14, and thus was relatively easy to pinpoint [133],[134], which also applied in the subsequent case of let-7 [135].
