This Week's Citation Classic

Readers of this blog may notice that my choices for classic papers come mainly from the evolution, ecology and molecular biology literature. This is not to imply that findings in other fields are less important, but rather that my command of the literature in other fields such as phylogenetics, developmental biology and cellular biology is less apt. However, even a caveman such as myself is familiar with the Homeobox discovery.

McGinnis W, Levine MS, Hafen E, Kuroiwa A, Gehring WJ. 1984. A conserved DNA sequence in homoeotic genes of the Drosophila Antennapedia and bithorax complexes. Nature 308: 428-33.

Homeotic genes determine when, where and how animal body segments develop. In other words, they tell cells in the developing embryo what kind of structures to make, i.e. legs, head, arms etc. Mutations in homeotic genes can result in dramatic changes in animal body plans, such as the antennapedia in the fruit fly that causes legs to develop instead of antennae (see photo). These genes, as the Nobelist Edward B. Lewis discovered, usually are co-linear in space and time with their segments of activity.
Many homeotic genes contain a common motif, a region termed the homeobox. This 180bp sequence encodes a 60 amino acid transcription factor, a protein that switches on and off other genes by binding to the relevant regions of DNA. The awesome thing about the Homeobox is that they are evolutionarily highly conserved, as McGinnis et al. discovered. The homeobox of the fruit fly is nearly identical to that of a wide variety of animals including the mouse and even humans! This is extraordinarily strong proof of common descent. Next time you see a fly, think about how you and she share a very similar stretch of DNA, the Rosetta Stone of life.

The master himself, PZ Meyers, covers Homeobox here.

Top photo from NIH. Fruit fly head showing the effects of the Antennapedia gene. This fly has legs where its antennae should be. Embryo cartoon from NobelPrize.org.