>>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 ?
>
[...]
>
>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 be most relevant to
>generate small adptive changes; alterations 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.
The unnamed authors of this passage write that "a significant limb
phenotype results...from the inappropriate activation of D11 at the
wrong time." Perhaps you can check the article again for us, Pim,
and describe the phenotype of the mutant. I'll bet that it's a
nonfunctional malformation.
Hardly a risky bet to make. Organisms do not like having their homeotic
genes tinkered with. Note that genetic redundancy is *redundancy for
an existing design* -- meaning that the organism has back-up systems
(alternative pathways) to buffer perturbations to its normal
developmental trajectory. This array of evolutionary "mechanisms"
>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 be most relevant to
>generate small adptive changes; alterations in the regulatory interactions
>between Hox proteins and their targets, through muations of the coding
>sequenc of Hox genes.
has not been demonstrated experimentally in animals to yield viable
phenotypes, which might provide a foundation for further morphological
change.
Rather, these "mechanisms" are post-hoc inferences resting on sequence
comparisons.
In short, the available experimental literature does not support the
claim that mutations to homeotic genes will yield novel functional
phenotypes, capable of competing with the wild type. Homeotic
mutants -- flies with legs where their antennae should be, or mice
with malformed jaws or inner ears -- are, adaptively speaking,
absolute dead-ends.
Paul Nelson