1102 THE STRUCTURE OF EVOLUTIONARY THEORY
in 15 years (and will no doubt extend, thereby rendering these pages obsolete, in just
a few additional years).
Not only do Hox genes exist in vertebrates, but also homologs for all Drosophila
Hox genes have been found, arranged in the same linear order on chromosomes, and
acting with the same colinearity in development along the A-P axis of the vertebrate
body. Moreover, vertebrate Hox genes have undergone fourfold replication and exist
as four paralogous sequences on four different chromosomes. (The vertebrate sister
taxon, amphioxus, has but a single Hox cluster, so we can make good inferences
about the timing of amplification in our lineage. The agnathan lamprey probably has
only three Hox sequences. Interestingly, and uniquely among deuterostomes, or any
other animal, the single Hox cluster of amphioxus has an "extra" or 14th Hox gene at
the 5' end—see Ferrier et al., 2000.) The vertebrate Hox genes can be arranged into
13 paralogy groups. (No vertebrate genome includes all 13 genes in any single
cluster. The mouse, for example, has 39 of the 52 possible genes—Ferrier et al.,
- The single sequence of amphioxus, however, does include a copy of each Hox
gene. The increase in potential number within each group occurred largely by
duplications of the posteriormost (5') homologs of Drosophila Hox genes.)
Lewis (1992, p. 1529) captured the excitement of this work in a single opening
adverb: "Astonishingly, mice and humans not only have cognates of the BX-C and
ANT-C genes in a single HOM-C, but the complexes occur in four sets, each in a
different chromosome." Slack et al. (1997, p. 867) echoes a consensus in designating
this discovery of deep homology as "the most spectacular achievement of molecular
developmental biology." Yet initial expectations certainly did not forecast emerging
realities. In a 1990 review, De Robertis described the decision to undertake an
experiment leading to the discovery of the first vertebrate homeobox gene in Xenopus
laevis (Carrasco, McGinnis, Gehring, and De Robertis, 1984—a good Orwellian
year). I was a bit saddened (but mostly amused) by the closing observation on the
counter-intuitively negative correlation that often emerges (or gets imposed by the
realities of laboratory culture) between youth and willingness to think the
unthinkable. To any graduate student reading this book, I can only say: Verbum
sapientiae... "We decided to try what seemed, at the time, a crazy experiment: to
isolate a gene similar to Antennapedia from frog DNA with McGinnis and Gehring's
fruit fly homeobox probes. There was little reason to believe that the frog DNA
contained such a gene or that the genes of such unrelated species would be
significantly similar. Still, we felt it was worth the attempt. Some of our colleagues
were skeptical that such an experiment could ever work, and two of our students
declined to help on those grounds."
The initial discovery of homology in genetic structure for arthropod and
vertebrate Hox did not seal the case for evolutionary meaning, since no one yet knew
how vertebrate Hox genes operated. Carrasco et al. (1984, p. 409) wrote of their
original discovery: "If the frog gene cloned here eventually turns out to have
functions similar to those of the fruit fly genes, it would represent the first
development-controlling gene identified in vertebrates." Evidence