Last year (September 2, 2010), I posted a Spec Tech column on “Monsters.” In that column I looked at the genetic basis for the Cyclops and the Werewolf. Here I’ll consider mutations that involve homeotic genes and the monstrous results that can arise. First we’ll look at how homeotic genes function in a flower, and from this example gain a clearer picture as to what a homeotic gene does. Then we will look at some of the crazy changes that can be wrought when homeotic genes are mis-expressed in an animal. From the point of view of evolutionists, and perhaps writers of science fiction, homeotic mutations suggest a mechanism by which new species can arise by sudden leaps.
Where Does a Flower Come From?
Evolutionarily speaking of course. Land plants have been around for over 400 million years, but flowering plants first appear in the fossil record about 140 million years ago. Darwin referred to the relatively sudden appearance of flowers as an “abominable mystery.” Since then the fossil record has improved and, moreover, we have the genetic information on how a flower is made. Which is all to say that the mystery of flowers isn’t quite so mysterious anymore.
To make a flower doesn’t look to be a simple task. Flowers have four major organs. Starting from the outside these are:
1. Sepals. These are usually green, enclose the bud and, after the flower opens, end up beneath the garish petals.
2. Petals. The part of the flower we usually notice first.
3. Stamens. The male organ that produces pollen.
4. Carpels. The female organ.
A flower looks to be fairly complex but genetic studies point to how mutations in only a few genes can have dramatic effects on the organ identity in a flower. For example, mutations that knock-out the function of a gene called AGAMOUS result in a loss of stamens and carpels. Instead the flower contains ONLY sepals and petals, with extra sets of these organs where the stamens and carpels used to be. Similarly, knockouts in other genes can result in the loss of sepals and petals. These are all homeotic genes and are responsible for establishing the developmental pathways that determine flower organ identity. Not surprisingly the homeotic genes encode transcription factors and as such regulate the expression of whole suites of genes.
If you’ve ever compared a domestic rose to a wild rose, you’ll have seen that the domestic rose has many more petals than its wild counterpart. This is because the domestic rose has a homeotic mutation that results in some of its potential stamens being converted to petals.
Now what happens if you have mutations in several of these floral homeotic genes, so that none of the flower organs can be made? You get something that looks structurally like a flower but instead of sepals, petals, stamens, and carpels you get…leaves. Concentric circles of leaves.
Which answers the original question of where does a flower come from. You start with the evolutionarily ancient program for making a leaf, but then add some new genetic programs that convert the leaf into the distinctive organs of the flower. And to initiate these developmental programs you have the master controllers we call homeotic genes.
(Department of Giving-Credit-Where-Credit-Is-Due: Much of the initial work in the area of flower homeotic mutations was performed in the laboratories of Enrico Coen and Elliot Meyerowitz)
Let’s Make a Monster
The previous section focused on what happens when you lose the function of a homeotic gene. But now what happens if you induce expression of a homeotic gene at a new location? The possibilities of this have been explored most thoroughly in fruit fly (Drosophila melanogaster). Eight homeotic genes regulate the identity of different regions within the fly. One of these genes is Antp, which specifies leg development. Antp is not normally expressed in the fly’s head (for reasons that if not obvious now soon will be), but under certain conditions can be expressed there. And when that happens one gets the antennapedia mutation, which produces exactly what its name suggests: legs growing where the antenna used to be. I’m sure you will have no trouble figuring out which is the normal fly head and which in the one with the antennapedia mutation below (hint: the one with the mutation is on the right).
There are other homeotic genes as well. For example, flies have a homeotic gene for the initiation of eye development (called EYELESS because if knocked out then the fly makes no eyes). If this gene gets expressed in other regions of the body, the fly develops little bumps of red eye tissue in those regions. But there’s more and in some ways this is even more amazing. Even though the eyes of insects and mammals are quite different, both have similar homeotic genes for the initiation of eye development. Mutations in the mouse Pax6 gene result in mice with small eyes. Mutations in the human aniridia gene result in eyes without an iris. To test the functional similarity of these genes throughout the animal kingdom, Walter Gehring and co-workers expressed the animal genes in the fly. What happens? Do you get a fly eye or a mouse eye? The image below, in which Pax6 is expressed in the fly’s leg, should answer these questions, the novel eyes being indicated by arrows. But that’s not the only location that eyes can be induced. Scientists have also expressed the mouse homeotic gene specifically in the fly’s jaw and produced a second set of eyes on the fly head located where the jaw used to be. The same approach is even successful in frogs, with expression of Pax6 able to induce the development of major components of the eye.
(Department of Truth-In-Advertising: Does the fly really have a million eyes? No, but as many as 16 have been reported for one fly. This is most assuredly closer to the truth than the monster in the original 1955 movie titled THE BEAST WITH A MILLION EYES, which had but a paltry pair to its name.)
1. “Snowball in Hell” by Brian Stableford. A look at human and animal evolution, and how we define what makes us human, as viewed through the lens of homeotic mutations. Originally published in Analog Dec. 2000, this received the Locus Poll Award for Best Novelette and is included in Stableford’s collection DESIGNER GENES: TALES OF THE BIOTECH REVOLUTION.
2. THE AMAZING SPIDERMAN, issue 100, Sept. 1971. The ultrabithorax homeotic mutation of Drosophila results in the fly growing an extra set of wings, not too far a remove from this issue in which Spidey grows two extra sets of arms. ‘Nuff said, true believer!