1100 THE STRUCTURE OF EVOLUTIONARY THEORY
historical constraint as an essential component of evolutionary theory and pattern.
Manak and Scott's (1994, p. 63) epitome of "hoxology" illustrates the centrality
of Lewis's original conceptions in a different guise:
Several rules governing homeotic gene function have been fairly well
conserved. (1) Genes are ordered along the chromosome in the same order as
their expression and function along the anterior-posterior axis of the animal.
(2) More genes are usually expressed in more posterior regions. (3) Loss of
gene function leads to loss of structures or to development of anterior
structures where more posterior structures should have formed. (4) Activation
of genes where they should be off, i.e. gain-of-function mutations, leads to
posterior structures developing where more anterior structures would normally
be found. To these generalizations we may add some molecular data. (5) Each
homeotic gene contains a single homeobox and encodes a sequence-specific
DNA-binding protein, which acts as a transcription factor. (6) Most of the
homeotic genes are transcribed in the same direction, with the 5' ends of
transcription units oriented toward the posterior end of the Hox cluster.The perfect colinearity of spatial order along the chromosome with the sequence
of morphological differentiation along the developing animal's anteroposterior axis
summarizes the most stunning conclusion of this research, and also generates most
other hoxological regularities. This central property of colinearity supplies a rationale
for Lewis's original concept of a gradient generated by tandem duplicates turning on
in spatial order along the chromosome. (The spatial sequence usually reflects a
temporal order as well, as morphologically anterior and genetically 3' units generally
operate first in ontogeny, with differentiation then proceeding temporally towards the
posterior. Some models of Hox evolution regard the temporal factor as primary (see
Duboule, 1992; Dolle et al., 1993; Deutsch and Le Guyader, 1998), and I shall
discuss this issue further in the last part of this section.)
The other morphological rules also follow from this central precept of
colinearity (Lewis could not have known about items 5 and 6 in the above list when
he devised his model). The rules for loss and gain-of-function mutations express this
key property in a particularly convincing manner. I have already discussed the classic
cases of four-winged and eight-legged flies as anteriorizations of posterior segments
caused by loss-of-function mutations. The ultimate loss, a fly developing with no Hox
gene function at all, leads to lethality, with the dead embryo as a grim and fascinating
manifestation of expected rules: a misfit bearing antennae on each of its segments
(Shubin et al., 1997, p. 644). (The antennae, or most anterior appendages, normally
develop with no Hox activity at all.) The famous Antennapedia mutant introduces
Hox activity into this anterior region and thus grows a leg in the antennal position.
Other gain-of-function mutations also cause posterior structures to move forward, as
expected. The first discovered gain mutation in the Hox genes, Contrabithorax (Cbx),
causes the second thoracic segment to differentiate