The body plan of most if not all animals is known to be influenced by the HOX genes, and individuals with mutant HOX genes are sometimes found with strange distorted bodies, perhaps with extra limbs or changes in the internal organs. My question is if drastic changes in the phenotype come from such small changes to the genes, why has the tetrapod body plan survived in so many forms without major changes to the skeleton. The only drastic change I can think of is the evolution of snakes from reptiles with legs, and to a lesser extent the evolution of dolphins and whales from land-mammals.

Why do we never see species of bird with extra wings, mammals with extra joints and bones in their limbs, or extra eyes for observing behind them etc?

That's a really good question.  I think the only logical reason is that such mutations are rarely advantageous.  Those you have mentioned are all linked with increasing fitness for a specific niche, but usually mutations in the HOX genes aren't.  When flies grow a second pair of wings, the wings are often deformed and make flying difficult.  Occasionally people and other vertebrates are born with extra limbs (e.g. http://arbroath.blogspot.com/2007/04/four-legged-stumpy-doing-well-update.html ) but when this happens, it causes problems, and the extra appendages aren't formed properly.

On top of the 'bad more often than good', even when a mutation may increase fitness of the individual, it may reduce the chances of attracting a mate and having offspring, thus making the overall fitness decrease.

Last edited by Peter Falkingham (27th May 2010 09:32:54)

I concur, an extra set of limbs is just too drastic a change.  However, once you leave the vertebrates, the situation can be a bit different.  For example, crustaceans have some sort of specialized appendage (feeding, swimming, etc) on just about every segment.  How many segments you have with one sort of appendage versus another - for example, how many pairs of more anterior feeding appendages before you transition to more posterior swimming appendages, is dependent on the extent of the expression of certain hox genes.  But it should be noted this example entails modifying a pre-existing structure that is already wired into the brain, rather than creating an entirely new one.

Hox genes are transcription factors - that means that they affect whether or not other genes get turned on in a certain time and place.  The genes that are affected by Hox genes are often involved in multiple facets of development.  So any changes in the Hox genes can change many aspects of development. 

Perhaps in very complex creatures with many body parts and hundreds of cell types like vertebrates, some aspects of development are "constrained" by the effect that these aspects have on other processes in development.  For example, changing the number of limbs doesn't only require a Hox gene to be expressed in a new place, but also requires many changes in bone, joint, muscle, skin, and nervous system development.  All of these changes have to happen together to work. 
So some things, like limb number (with snakes as a major exception) might be constrained.  However, there are some other interesting body plan changes in vertebrates, for example the evolution of wings from forelimbs in bats and birds, and the evolution of bipedality in primates and reptiles (as seen in birds and some dinosaurs).

By coincidence a paper published today in PNAS gives an example of divergence in a hox gene function between zebrafish and mouse. see:

http://www.pnas.org/content/early/2010/ … 7.abstract

I'll just add a couple of quick points to what others have said. For one thing, major changes in the tetrapod body plan are not THAT rare. Ichthyosaurs, for example, are extinct reptiles with superficially dolphin-like bodies. Caecilians are amphibians that have lost their limbs, and limb loss has also occurred multiple times in lizards (snakes, which evolved from within lizards, represent one such occurrence).

However, it's true that major changes normally happen gradually, not in one giant mutational leap. Why should this be the case, if single HOX mutations can cause huge alterations in body structure?

For one thing, new structures produced by such changes are typically not very well integrated with the rest of the animal's anatomy, as Peter and Ajna pointed out. From an engineering perspective, it would be difficult to just add an extra pair of limbs to any tetrapod and achieve a viable design, unless it was also possible to make a lot of other changes simultaneously.

From a more evolutionary perspective, it's unlikely that a large change would be advantageous even if it were biomechanically viable. Most animals are relatively well adapted to their environments already, and one classic analogy compares a well adapted species to a microscope that is almost in perfect focus. A small adjustment of the knob in the right direction would improve the focus further, but a large adjustment would overshoot and make matters worse. It's not a perfect analogy by any means, but I think it does capture an important point about the evolutionary process. Big, sudden changes are less likely to be helpful than small, incremental ones.