13. Hox Genes and Arthropod Diversity
197
been documented in a wide range of species by William Bateson, who coined the
term "homeotic" for such transformations (Bateson 1894).
Drosophila contains two principal clusters of genes that give rise to such homeotic
mutant phenotypes (Mahaffey and Kaufman 1987; Lawrence and Morata 1994).
These genes derive from a single ancestral gene cluster that was split by a chromosome rearrangement relatively recently, during the radiation of the Drosophilids
(Von Allmen et at. 1996). The homologous genes of other insects still comprise a
single tightly linked cluster (Denell et at. 1996). Mutations in genes at one end of
this cluster affect the head of the animal, while genes at the other end are needed
for the normal development of the most posterior segments of the abdomen. The
plan of the body from front to back is reflected in the sequence of the genes on the
chromosome.
What these genes do became clear from genetic studies pioneered by E. B. Lewis
at the California Institute of Technology, for which he was awarded the Nobel prize
in 1995 (Lewis 1995). [Interestingly, some of Lewis' insights were informed by
earlier studies, in Japan, of the homologous "E complex" genes in the silk moth
during the 1940s and 50s, (Tazima 1964)]. Lewis showed that when the Hox genes
were mutated, the normal diversity of segments was lost (Lewis 1963, 1978). When
all genes in one half of the cluster were lost, all segments in the posterior thorax
and abdomen of the fly developed like the wing bearing segment. It has since been
shown in other insects that when the entire set of Hox genes are lost, each segment
develops structures characteristic of the normal antennal segment (Beeman et at.
1993). Thus the Hox genes are required, not primarily for making segments, but for
specifying the different pathways of development that each segment will follow.
We now know that the products of these genes are transcription factors - nuclear
proteins that turn other genes on and off (Affolter et at. 1990). All of the genes in
the Hox cluster encode related transcription factors with structurally similar, but
biologically distinct, DNA binding domains called homeodomains. (Homeodomains
have since been found in many other proteins, in addition to the Hox genes). Each
of the Hox proteins is expressed in a restricted subset of segments, so dividing the
body of the fly into a series of domains with different molecular labels (Akam
1987).
There are not enough Hox genes to give each segment a different label, though
it is clear that in Drosophila each segment does have a unique morphology. There
are several explanations for this (Lawrence and Morata 1994). Genes other than
the Hox family provided a component of the address, particularly in the most anterior and posterior parts of the animal; genes are used in combination in some segments, and a single Hox gene can be expressed in different spatial and temporal
patterns in different segments, affecting the type of segment that develops (CastelliGair and Akam 1995).
Genes of the Hox cluster are not unique to insects. Almost as soon as they were
first cloned from Drosophila, homologous sequences were identified in vertebrates.
These proved to encode closely related transcription factors of the same Hox family
(McGinnis et at. 1984; Gehring 1987; McGinnis and Krumlauf 1992). Not only are
197
been documented in a wide range of species by William Bateson, who coined the
term "homeotic" for such transformations (Bateson 1894).
Drosophila contains two principal clusters of genes that give rise to such homeotic
mutant phenotypes (Mahaffey and Kaufman 1987; Lawrence and Morata 1994).
These genes derive from a single ancestral gene cluster that was split by a chromosome rearrangement relatively recently, during the radiation of the Drosophilids
(Von Allmen et at. 1996). The homologous genes of other insects still comprise a
single tightly linked cluster (Denell et at. 1996). Mutations in genes at one end of
this cluster affect the head of the animal, while genes at the other end are needed
for the normal development of the most posterior segments of the abdomen. The
plan of the body from front to back is reflected in the sequence of the genes on the
chromosome.
What these genes do became clear from genetic studies pioneered by E. B. Lewis
at the California Institute of Technology, for which he was awarded the Nobel prize
in 1995 (Lewis 1995). [Interestingly, some of Lewis' insights were informed by
earlier studies, in Japan, of the homologous "E complex" genes in the silk moth
during the 1940s and 50s, (Tazima 1964)]. Lewis showed that when the Hox genes
were mutated, the normal diversity of segments was lost (Lewis 1963, 1978). When
all genes in one half of the cluster were lost, all segments in the posterior thorax
and abdomen of the fly developed like the wing bearing segment. It has since been
shown in other insects that when the entire set of Hox genes are lost, each segment
develops structures characteristic of the normal antennal segment (Beeman et at.
1993). Thus the Hox genes are required, not primarily for making segments, but for
specifying the different pathways of development that each segment will follow.
We now know that the products of these genes are transcription factors - nuclear
proteins that turn other genes on and off (Affolter et at. 1990). All of the genes in
the Hox cluster encode related transcription factors with structurally similar, but
biologically distinct, DNA binding domains called homeodomains. (Homeodomains
have since been found in many other proteins, in addition to the Hox genes). Each
of the Hox proteins is expressed in a restricted subset of segments, so dividing the
body of the fly into a series of domains with different molecular labels (Akam
1987).
There are not enough Hox genes to give each segment a different label, though
it is clear that in Drosophila each segment does have a unique morphology. There
are several explanations for this (Lawrence and Morata 1994). Genes other than
the Hox family provided a component of the address, particularly in the most anterior and posterior parts of the animal; genes are used in combination in some segments, and a single Hox gene can be expressed in different spatial and temporal
patterns in different segments, affecting the type of segment that develops (CastelliGair and Akam 1995).
Genes of the Hox cluster are not unique to insects. Almost as soon as they were
first cloned from Drosophila, homologous sequences were identified in vertebrates.
These proved to encode closely related transcription factors of the same Hox family
(McGinnis et at. 1984; Gehring 1987; McGinnis and Krumlauf 1992). Not only are