The Hox genes are a set of transcription factors that exhibit an unusual property: they provide a glimpse of one way that gene expression is translated into metazoan morphology. For the most part, the genome seems to be a welter of various genes scattered about almost randomly, with no order present in their arrangement on a chromosome — the order only becomes apparent in their expression through the process of development. The Hox genes, on the other hand, seem like an island of comprehensible structure. These are all genes that specify segment identity — whether a segment of the embryo should form part of the head, thorax, or abdomen, for instance — and they’re all clustered together in one (usually) tidy spot.

Within that cluster, we see further evidence of order. Look at just the Drosophila part of the diagram below: there are 8 Hox genes in a row, and their order within that row reflects the order of expression in the fly body. On the left or 3′ end of the DNA strand, lab (labial) is expressed in the head, while Abd-B (Abdominal-B) is expressed at the end of the abdomen.

Schematic of relationship between Drosophila and mouse Hox genes. Hox genes are shown as colored boxes in their order on the chromosome. Orthologous genes between Drosophila and mouse, and paralogous mouse genes are shown color-coded.

Knocking out individual Hox genes in the fly causes homeotic transformations — one body part develops into another. These genes are early actors in the cascade of interactions that enable the development of morphologically distinct regions in a segmented animal — the activation of a Hox gene from the 3′ end is one of the earliest triggers that leads the segment to develop into part of the head.

Now look at the mouse part of the diagram above. We vertebrates have Hox genes that are homologous to the fly Hox genes, and they’re also clustered in discrete locations with 3’→5′ order reflecting anterior→posterior order of expression. There are differences — the two most obvious that we have more Hox genes on the 5′ side (these correspond to expression in the tail—flies do not have anything homologous to the chordate tail), and vertebrates also have four banks of Hox genes, HoxA, HoxB, HoxC, and HoxD. This complicates matters. Vertebrates have these parallel, overlapping sets of Hox genes, which suggests that morphology could be a product of a combinatorial expression of the genes in the four Hox clusters: there could be a Hox code, where identity can be defined with more gradations by mixing up the bounds of expression of each of the genes.

[Read more…]