Historical Constraints and the Evolution of Development 1163
If we now turn our attention to these "conserved roles in arthropods and
chordates," at least three sources of evidence underscore the central conclusion of this
section: that the evolution of differentiated and specialized Bauplane from a
presumably homonomous common ancestor proceeds— paradoxically, and contrary
to the scenario of Lewis's (1978) original hypothesis about Hox genes—by reduction
and restriction, rather than by addition of genes or expansion of their domains of
activity.
- Specialization of anatomy sometimes correlates with deletion or unem-
ployment of Hox genes, or their redeployment to other functions. For example, Zen,
the insect ortholog (in both structure and position) to vertebrate Hox3, exhibits no
Hox function and is not expressed along the AP axis of the developing larva, but
plays some role instead in the formation of extra-embryonic membranes. In a paper
that wins, by acclamation, the Steinbeckian prize for title parodies ("Of mites and
Zen"), Telford and Thomas (1998) cloned the homolog of Drosophila Zen in the
orbatid mite Archegozetes. They found expression of this chelicerate homolog "in a
discrete antero-posterior region of the body with an anterior boundary coinciding
with that of the chelicerate homolog of the Drosophila Hox gene proboscipedia" (p.
591). This fascinating result suggests that zen may have lost its Hox function in
Drosophila as a consequence of functional redundancy due to overlap with another
Hox gene.
Taking the argument further, Telford and Thomas present evidence that the
Drosophila pair-rule gene fushi tarazu may also be "a divergent Hox gene that has
adopted a new role" (p. 594; see also Dawes et al., 1994, on a locust homolog of fushi
tarazu that shows no pair-rule function). These observations on the original roles of
Drosophila zen and fushi tarazu suggest "that the original complement of arthropod
Hox genes must be revised from eight to ten" (Telford and Thomas, 1998, p. 594),
thus emphasizing the role of gene loss in the specialization of body plans. - Stasis or slow change in Hox genes indicates their conserved role in
evolution. Akam et al. (1994), in a section of their paper entitled "Hox genes that got
away," contrast the conservation of Hox genes in insects (as documented by high
levels of sequence similarity among taxa) with much higher rates of divergence in
homeobox genes that do not now function within the Drosophila Hox series, but may
have belonged to the Hox cluster of an arthropod common ancestor: the maternally
expressed bicoid (encoding the morphogen that produces a crucial AP gradient in the
early syncytial embryo), the pair-rule gene fushi tarazu, and the two zen genes. The
putative orthologs of fushi tarazu in other insects "are almost unrecognizable outside
of their homeodomains, and have accumulated approximately 10 times as many
changes in their homeodomains as have homeotic [i.e., Hox] genes in the same
comparisons" (Akam et al., 1994, p. 209). The authors then generalize about these
non-Hox homeobox genes (p. 214): "We think that these genes may be derived...
from Hox genes which, in the lineage leading to Drosophila, have escaped from the
conservative selection that characterizes homeotic genes."