Jonathan Clarke wrote, in part:
>The problem is not intractable. Molecular genetics can give
>us phylogenies and mechanisms by which new body plans develop.
>
>[...]
>
>We know a lot more than we did 20 years
>ago, especially about how changes body plans happen at the level
>of developmental biology and genetics [...]
I wonder if you could say more, Jonathan, about how you see
molecular genetics having illuminated how new body plans develop,
or how they change viably.
Homeobox ?
Then, in 1984, biologists working with fruit flies found a bit of DNA they called the
homeobox. The homeobox got its name because it first surfaced as a leitmotif in homeotic
genes--those known to specify body-part formation. (One of them, if it mutates, plunks legs
on a fly's head where its antennae are supposed to be.) These homeotic genes were known
to be gathered together in clusters on a strand of DNA, arranged in a sequence that
uncannily mimics the order of the body parts in the finished fly. For example, the genes in
one cluster control the design and fabrication of the fly's head and upper thorax; the genes in
the next cluster down the line define the fly's lower thorax and abdomen. Researchers found
that in every one of these body-forming genes this one stretch of DNA--the
homeobox--was the same.
So what? you might ask. Some biologists were similarly unimpressed, until the homeobox
began turning up in development-related genes in all kinds of other creatures: worms,
African clawed frogs, mice-- and humans. Its recurrence in animals all the way from the
low-rent basement of evolution right up to the penthouse suggested that the homeobox was
no mere curio but something crucial to development in a vast array of living things. Indeed,
by 1990 it was clear that the homeobox was part of a basic genetic switch, turning on
(whenever it's appropriate) other genes in the cascade of events by which initially featureless
cells are trained for the thousands of different roles they'll eventually assume. William
McGinnis, a molecular biologist at Yale, found he could even transplant
homeobox-containing genes from a mouse or a human to a fruit fly and have the genes
work. So the study of worms and flies no longer seemed a blind alley, but rather a royal
road to the secrets of morphogenesis.
<...>
Genetic Redundancy of the Homeotic Complex
Permits Evolution of the Body Plan
With the exception of some of the more anterior genes in the complex,
mutations in many hox genes resulted in only minor phenotypes that did
not affect morphology greatly. Often, in mutations affecting vertebral
structure, only one side of the animal was affected, suggesting that there
is some plasticity in the response hox code. Hox genes have long
thought to play an important role in limb development. However, when
limb genes such as A11 or D11 were made, the phenotypes were
hardly detectable. On the other hand, once two mutations were put
together, the effects were dramatic. For example, the absence of both
A11 and D11 results in a severe and life threatening reduction in the
radius and ulna. What this result tells us is that the redundancy of the
Hox complex permits some flexibility in the response to mutational
change.
Redundancy permits a rich potential to allow for evolutionary
alterations of the body plan, through the following mutational changes:
variations in the number of homeotic genes, by deletion and or
duplication;
increases in the number of hox complexes through whole
complex duplication events;
mutations affecting the timing, position or level of homeotic gene
activation, which may bemost relevant to generate small adptive
changes;
aterations in the regulatory interactions between Hox proteins
and their targets, through muations of the coding sequenc of Hox
genes.
Recently, heterochronic mutations have been made within the hox gene
complex by changing the position of a given gene within the complex.
When hoxD11 is targeted into D13, a significant limb phenotype results
- not from the inactivation of hoxD13 itself but from the inappropriate
activation of D11 at the wrong time.