198
M.Akam
the sequences conserved, but also three key characteristics of these genes. First, the
Hox genes are clustered in vertebrates, as they are in insects. Second, they are
expressed in restricted domains along the head/tail axis of the body. Third, when
the function of these genes is disrupted, homeotic transformations are produced
analogous to those seen in flies. For example, when the Hox gene A9 of the mouse
is "knocked out", the most anterior of the lumbar vertebrae transforms into a thoracic vertebra (Fromental-Ramain et al. 1996).
These conserved characteristics suggest that the last common ancestor of insects and vertebrates possessed clustered Hox genes that were differentially expressed along the antero-posterior axis of the body, and were used to control the
specific differentiation of different regions of the body, which mayor may not already have been segmented (Akam 1989). Flies and humans use the same machinery to build their head-tail axis!
3 The Origins and Evolution of Hox Genes
Vertebrates and insects are representatives of two ancient lineages within the metazoa
- the deuterostomes and the protostomes respectively. These lineages split near
the base of the radiation of the metazoan phyla. How old then are the Hox gene
clusters? The answer seems to be that the Hox clusters are a shared derived characteristic of the metazoa. They are by no means the only such characteristic, and here
I disagree with the suggestion that these genes alone, as the Zootype, can be used to
define the metazoa (Slack et al. 1993).
Hox genes belong to a larger family of transcription factors, the homeobox genes,
which all encode transcription factors containing homeodomains. This protein domain is older than the metazoa - homeobox genes are known from plants and
fungi as well as animals. Interestingly, in yeast and several other fungi the homeobox
genes are specifically involved in controlling the choice between different cell fates,
e.g. the mating types. The same seems to be true for the many classes of homeobox
genes in animals. More than twenty classes of homeobox genes arc recognised in
animals, deriving from perhaps 4 or 5 prototypes that existed in the last common
ancestor with plants and fungi (Biirglin 1995). This homeobox gene family appears
to have radiated particularly dramatically in the animal kingdom, some time after
the split of the first animals from the plants and fungi, but before the separation of
the protostomes from the deuterostomes.
The precise sequence of gene duplications, and gene cluster duplications, that
gave rise to the Hox gene family is not yet clear. At least one duplication of a protoHox cluster occurred, to give rise to Hox and para-Hox genes (Brooke et al. 1998).
though whether this happened before or after the divergence of the cniadarians
from the triploblasts is uncertain.
We can now say with some certainty that a cluster of at least 7 distinct Hox
genes predated the radiation of the triploblast phyla. Hox genes have been sampled
in nemerteans (non-segmented worms), annelids (segmented worms) and molluscs
M.Akam
the sequences conserved, but also three key characteristics of these genes. First, the
Hox genes are clustered in vertebrates, as they are in insects. Second, they are
expressed in restricted domains along the head/tail axis of the body. Third, when
the function of these genes is disrupted, homeotic transformations are produced
analogous to those seen in flies. For example, when the Hox gene A9 of the mouse
is "knocked out", the most anterior of the lumbar vertebrae transforms into a thoracic vertebra (Fromental-Ramain et al. 1996).
These conserved characteristics suggest that the last common ancestor of insects and vertebrates possessed clustered Hox genes that were differentially expressed along the antero-posterior axis of the body, and were used to control the
specific differentiation of different regions of the body, which mayor may not already have been segmented (Akam 1989). Flies and humans use the same machinery to build their head-tail axis!
3 The Origins and Evolution of Hox Genes
Vertebrates and insects are representatives of two ancient lineages within the metazoa
- the deuterostomes and the protostomes respectively. These lineages split near
the base of the radiation of the metazoan phyla. How old then are the Hox gene
clusters? The answer seems to be that the Hox clusters are a shared derived characteristic of the metazoa. They are by no means the only such characteristic, and here
I disagree with the suggestion that these genes alone, as the Zootype, can be used to
define the metazoa (Slack et al. 1993).
Hox genes belong to a larger family of transcription factors, the homeobox genes,
which all encode transcription factors containing homeodomains. This protein domain is older than the metazoa - homeobox genes are known from plants and
fungi as well as animals. Interestingly, in yeast and several other fungi the homeobox
genes are specifically involved in controlling the choice between different cell fates,
e.g. the mating types. The same seems to be true for the many classes of homeobox
genes in animals. More than twenty classes of homeobox genes arc recognised in
animals, deriving from perhaps 4 or 5 prototypes that existed in the last common
ancestor with plants and fungi (Biirglin 1995). This homeobox gene family appears
to have radiated particularly dramatically in the animal kingdom, some time after
the split of the first animals from the plants and fungi, but before the separation of
the protostomes from the deuterostomes.
The precise sequence of gene duplications, and gene cluster duplications, that
gave rise to the Hox gene family is not yet clear. At least one duplication of a protoHox cluster occurred, to give rise to Hox and para-Hox genes (Brooke et al. 1998).
though whether this happened before or after the divergence of the cniadarians
from the triploblasts is uncertain.
We can now say with some certainty that a cluster of at least 7 distinct Hox
genes predated the radiation of the triploblast phyla. Hox genes have been sampled
in nemerteans (non-segmented worms), annelids (segmented worms) and molluscs