378 CHAPTER 15Hox genes and the genetic toolkit
Long before DNA was identified as the basis of heredity, geneticists had described
what they called homeotic mutations in Drosophila and other species. These are
mutations that transform a structure into a different structure. For example, the
Antennapedia (Antp) mutation in Drosophila transforms antennae into legs (see
Fig ure 4.18), and the Ultrabithorax (Ubx) mutation turns halteres (balancers) into
wings (FIGURE 15.8).
To appreciate the significance of these mutations, we need to be acquainted
with a few details about arthropod segments. In arthropods such as crustaceans,
the body consists of multiple segments, almost all of which bear a pair of serially
homologous appendages with similar basic structure. Appendages on the most
anterior segments are modified as mouthparts, and those on the trunk serve for
locomotion. In insects, which are descended from crustaceans, three distinct seg-
ments make up the thorax, each with a pair of legs, and the posterior segments are
legless and compose the abdomen. In most insects, the second and third thoracic
segments (T2 and T3) each have a pair of wings. In the true flies (order Diptera),
such as Drosophila, the T3 wings are modified into small structures, the halteres,
that are used for balance rather than flight. The Diptera are one of the insect
orders in which the juvenile stage, the larva, has a radically different form than the
adult. The adult structures, such as legs, wings, and halteres, develop from special
masses of cells, the imaginal discs, within the body of the larva.
Starting in the 1970s, geneticists realized that some of the homeotic mutations
in Drosophila change the identity of a segment. For example, mutations in the Ubx
locus change the T3 segment into a second T2 segment, and therefore the halteres
into wings (see Figure 15.8). Deleting the gene has the same effect. Mutations of
other genes that affect characteristics of the wing affect the duplicated wing just
as they affect the normal wing on T2. Thus, it was suggested that the normal Ubx
gene regulates the transcription of the diverse genes that together produce a T3
segment; if mutation or deletion of the Ubx gene causes failure of regulation, the
segment develops into a “default” state, T2. Antp and Ubx are two of eight genes,
in two clusters, that control the anterior-posterior identity of body segments, in
the same order as the genes’ positions along the chromosome (FIGURE 15.9). T he
expression of each of these genes along the anterior-posterior axis of the develop-
ing fly corresponds to the segments whose identity the gene affects. These genes
encode transcription factors. The part of the genes’ sequence that encodes the
DNA-binding domain of the protein is now called the homeobox, and the genes
are called homeotic selector genes, or Hox genes.
The Hox genes are part of a gene regulatory network—a set of interacting regu-
latory genes and the genes they regulate—that controls the developmental pathway
that specifies the anterior-posterior body pattern (FIGURE 15.10). To greatly over-
simplify, mRNAs of two of the mother’s genes (bicoid, nanos) are deposited in the
egg. The mRNAs and the proteins they encode form in anterior-posterior concentra-
tion gradients. Depending on their concentration, several gap genes are transcribed
in different broad domains. Gap gene proteins activate pair-rule genes, such as fushi
tarazu (ftz), in seven transverse bands. Their protein products bind to and activate a
group of segment polarity genes that determine the boundaries of 14 segments in the
developing larva. The transcription factors produced by gap, pair-rule, and segment
polarity genes all act to initiate or repress transcription of the Hox genes (which also
repress each other). And as we have seen, the Hox genes that are expressed in each
segment directly or indirectly regulate transcription of many genes that determine
the segment’s form and features. The end points of the pathway are the synthesis of
the proteins that define the features of each cell in a particular tissue in a particular
part of a segment. Complex regulatory pathways of this kind are characteristic of
development of most of the morphological features of multicellular organisms.Futuyma Kirkpatrick Evolution, 4e
Sinauer Associates
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Evolution4e_15.08.ai Date 11-02-2016
(B)(A)HaltereFIGURE 15.8 A homeotic mutation.
(A) A wild-type Drosophila melanogaster
has a single pair of wings, borne on the
second thoracic segment, and a pair of
small winglike structures called halteres,
borne on the third thoracic segment.
(B) In a fly carrying mutations in the Ul-
trabithorax (Ubx) gene, the third thoracic
segment has been transformed into
another second thoracic segment, bear-
ing wings instead of halteres. (Photos
courtesy of E. B. Lewis.)15_EVOL4E_CH15.indd 378 3/22/17 1:30 PM