The Homeobox

Homeobox-containing, or "hox," genes are responsible for the big decisions of development rather than the details of engineering. Fruit flies with a particular mutation in one of their many hox genes, for example, will develop an anatomically normal leg - in the spot where an antenna should be.

The homeobox is a 180-basepair sequence of DNA that has been found in all homeotic genes (and also in many other regulatory genes).

Much of the embryonic development is controlled by the egg's own genes. They are divided into three functional groups

  • The gap-genes lay the foundations of a rough body plan along the head-to-tail axis
  • the pair rule-genes govern formation of every second body segment
  • the segment polarity-genes refine the head-to-tail polarity of each individual segment, meaning that the head-end and the tail-end of a segment look different.

Homoeotic genes are almost identical in very different species. We can study homeotic genes in the fruit fly to learn about the same genes the control development in a human or mouse. These groups of genes have remained relatively unchanged throughout evolutionary history.

Whether from flies, worms, mice, or humans, all homeotic genes contain a segment called a homeobox, made up of 180 base pairs of DNA, which codes for an important domain of a transcription factorÑa protein that regulates the activity of other genes. ÊÊÊ Similar genes, in the same order, control the development of the front and back part of the bodies of flies and mice.

These homeobox-containing genes lie on a single chromosome in the fly (top row of colored squares) and on four separate chromosomes in mammals (lower rows of squares). The genes are color coded to match the parts of the body in which they are expressed. ÊÊÊ

While flies have just one cluster of homeobox-containing genes that lies on a single chromosome, mammals have four similar clusters lying on four separate chromosomes. In each cluster, the genes located at one end direct the development of the anterior part of the body, while the genes at the other end control the formation of the posterior part.

Mutations in homeotic genes lead to profound changes in the anatomy of the organism

Mutation causes an extra thoracic segment, and an extra set of wings.

 

Mutation causes legs to grow from the wrong segment, in this case, where the antennae are supposed to be.

 

Similar abnormalities can be induced in mice by mutating homeotic genes

  • mice develop with missing leg bones
  • mice deveop missing vertebrae
  • mice develop missing their entire posterior ends

 

 

 

In humans, a homeotic gene is thought to play a role in the development of irises - the part of the eye that opens and closes the pupil dependent on the light intensity. In rare cases, humans are born without irises, a condition called aniridia.

 

 

Implications

The discovery of homeobox genes shows that small mutations in a base pair of DNA can result in profound physical changes - most of these are lethal.

The conservation of homeobox genes - species from human to worm - shows a link between these animals, evidence of common ancestry

Homeobox genes supports the Theory of Evolution and punctuated equilibrium, by showing that simple mutations can result in large changes of morphology.

Article - Genetic Alchemy - Turning Lobsters into Fruit Flies

Tutorials - http://www.nobel.se/medicine/laureates/1995/illpres/index.html (more on homebox genes)

Assignment - Homeobox Gene Coloring Worksheet

Video - Shown in class - fruit fly mutations

Web Assignment - Homeobox Genes