The gene families for miR-10, miR-196 and miR-615 are located in the regions of homeobox (HOX) clusters within the genome of vertebrates [26]. HOX genes encode homeodomain-containing transcription factors that are essential for embryonic development [27]. In many species, they are organized in tightly linked clusters along the chromosome. Activation and silencing of HOX genes requires preservation of their native order within each cluster, and the evolutionary patterns of both miR-10 and miR-196 closely resemble that of the HOX genes in vertebrates [28]. Three miR-196 genes have been found. The miR-196a-1 gene is located on chromosome 17 (17q21.32) at a site between HOXB9 and HOXB10 genes, and the miR-196a-2 gene is located at a region between HOXC10 and HOXC9 on chromosome 12 (12q13.13) (Fig. 1) [28]. The gene for miR-196b is located in a highly evolutionarily conserved region between HOXA9 and HOXA10 genes, on chromosome 7 (7p15.2) in human beings and chromosome 6 (6qB3) in mice (Table 1 and Fig. 1) [29]. miR-196a-1 and miR-196a-2 genes transcribe the same functional mature miRNA sequence (3′-GGGUUGUUGUACUUUGAUGGAU-5′), whereas miR-196b gene produces a small RNA (3′-GGGUUGUUGUCCUUUGAUGGAU-5′), which differs from the sequence of miR-196a by one nucleotide [28]. Many miRNAs are fairly well-conserved among vertebrates; in fact, they are as conserved as the most conservative phylogenetic footprints [30]. Although miRNAs are very small in size, they carry a strong phylogenetic signal [28, 31]. miR-196 homologues are detectable in a variety of vertebrates.