Genomic Evolution of Hox Gene Clusters
The family of Hox genes, which number 4 to 48 per genome depending on the animal, control morphologies on the main body axis of nearly all metazoans. The conventional wisdom is that Hox genes are arranged in chromosomal clusters in colinear order with their expression patterns on the body axis. However, recent evidence has shown that Hox gene clusters are fragmented, reduced, or expanded in many animals-findings that correlate with interesting morphological changes in evolution. Hox gene
... on. Hox gene clusters also contain many noncoding RNAs, such as intergenic regulatory transcripts and evolutionarily conserved microRNAs, some of whose developmental functions have recently been explored. Hox genes encode a large family of closely related transcription factors with similar DNA binding preferences. They have not been found in sponges, protozoa, or plants but are present in multiple copies in cnidarians and all bilaterian animals. As a distinct branch of the homeobox gene superfamily, Hox genes have been a source of fascination since their discovery because of their powerful functions in diversifying morphology on the head-tail axis of animal embryos. This power is revealed by dramatic duplications of headtail axial body structures, called homeotic transformations, that can form when one or more of the Hox genes are activated in inappropriate axial positions in developing animals (1). The different HOX transcription factors are expressed in distinct, often overlapping, domains on the head-tail body axis of animal embryos (Fig. 1A) , and assign different regional fates to these axial domains. As development proceeds, "head" HOX proteins specify the cell arrangements and structures that result in (for example) chewing organs, "thoracic" HOX proteins specify (for example) locomotory organs, and "abdominal" HOX proteins specify (for example) genital and excretory organs. Not surprisingly, extreme homeotic transformations are lethal at early stages of development. Hox genes are also of great interest because there is abundant correlative evidence that changes in Hox expression patterns and protein functions contributed to a variety of small and large morphological changes during animal evolution (2).