1104 THE STRUCTURE OF EVOLUTIONARY THEORY
autopods. There is therefore a correlation between the extreme 5' location of
the Hoxd- 13 gene within its complex, its last position in the temporal
sequence of activation and its involvement in the patterning of the last-
appearing structures. The Hoxd- 13 phenotype may thus be considered as
resulting from a block in a developmental sequence. This arrest occurs at the
end of the process and corresponds to the time at which this gene is supposed
to become active. Consequently, only those structures appearing at the end of
the process, or parts of those structures still developing at this stage, will be
altered.In a corresponding manner, gain-of-function mutations often yield the expected
effects of posteriorization. Kessel et al. (1990) induced overexpression of the mouse
Hoxa- 7 gene (previously called Hox-1.1) by inserting a promoter sequence of chicken
DNA. Two results indicate a forward movement of posterior structures: (i) the first
two vertebrae, the atlas and axis, became simplified, assuming a "structure
characteristic of more posterior vertebrae" (1990, p. 302); (ii) the last cervical
vertebra of one animal developed a pair of ribs and assumed the form of the next
posterior series of thoracic vertebrae.
Kessel and Gruss (1991) then induced overexpression by application of retinoic
acid. "Posterior transformations occurred along the complete body axis after RA
administration on day 7 of gestation and were accompanied by anterior shifts of Hox
gene expression domains in embryos" (1991, p. 89). In a particularly interesting
result, Lufkin et al. (1992) ectopically expressed Hoxd- 4 (previously Hox-4.2) in
regions of the developing head anterior to its usual boundary of expression in somites
of the cervical vertebrae. "This ectopic expression results in a homeotic
transformation of the occipital bones towards a more posterior phenotype into
structures that resemble cervical vertebrae" (p. 835). Phyletic inference is
treacherous, and absurd claims have been made in misanalogies between phyletic
history and developmental anomaly. But a transformation of skull bones towards the
identity of vertebrae does induce thoughts of a presumably more homonomous
ancestral vertebrate.
Interestingly, the A-P axis of the vertebrate limb also seems to follow the same
rules of colinearity. Morgan and Tabin (1994) demonstrated the importance of the
Hoxd series in differentiation of the chick limb bud. They observed expression of
successive 5' genes in progressively more posterior regions. Overexpression of Hoxd-
11 in regions anterior to its normal domain led to the growth of an additional phalanx
in digit 1 (which normally has one, while subsequent digits have 2, 3, and 4
respectively, excluding the terminal claw)—"leading to a morphology similar to that
of digit 2" (p. 183), a posteriorization anticipated in gain-of-function regimes. Ectopic
expression of Hoxd- 11 in anterior regions of the chick wing that normally grow no
skeletal elements at all induced the growth of a supernumerary digit (resembling digit
2 in morphology) at the wing's anterior edge.
Tickle (1992) noted the similarity of Hoxd expression in the chick wing to