Hox genes are master transcription factors that determine the “identity” of each region along the anterior-posterior (head-to-tail) axis of the body. They are remarkably conserved from fruit flies to mammals.
Basic Knowledge
Hox genes (homeotic genes): A group of transcription factors containing a homeodomain (a 60-amino-acid DNA-binding domain). They determine the morphology of each region along the body axis.
History of discovery: They were discovered through homeotic mutants of fruit flies, such as Antennapedia (legs grow in place of antennae) and Ultrabithorax (an extra pair of wings develops). It was found that these traits are controlled by Hox gene clusters.
Edward Lewis, Christiane Nüsslein-Volhard, and Eric Wieschaus received the 1995 Nobel Prize in Physiology or Medicine.
Principle of collinearity: The order of Hox genes on the genome corresponds to their expression regions along the body axis (spatial collinearity). Hox genes at the 5′ end of the genome are expressed toward the head, while those at the 3′ end are expressed toward the tail. This principle is conserved in fruit flies, mice, and humans.
Fruit flies have 8 Hox genes (one cluster), while vertebrates have 4 clusters × 13 genes = up to 39 Hox genes. Their number increased through genome duplication.
Answer: The principle of collinearity states that the order of Hox genes from the 5′ end to the 3′ end of the genome corresponds to their expression pattern from the head to the tail of the body axis. Its evolutionary significance is thought to be that the correspondence between genomic order and body-axis pattern enables efficient long-range chromatin regulation of Hox gene clusters. In an Antennapedia mutation, a Hox gene is expressed ectopically in the antennal region of the head, activating the developmental program for legs in cells that would normally form antennae. Hox genes function as master switches that instruct cells which organs to form.
- Hox genes = transcription factors that determine the morphology of each region along the body axis
- Principle of collinearity = genomic order corresponds to expression regions along the body axis
- Fruit flies have 8 genes; vertebrates have up to 39 genes in 4 clusters
- Antennapedia = ectopic Hox expression in the antennal region → legs grow
- Lewis, Nüsslein-Volhard, and Wieschaus = 1995 Nobel Prize
- Homeodomain = DNA-binding domain, highly conserved among Hox proteins
Practice
- Explain why Hox genes are called master transcription factors.
- State from an evolutionary viewpoint why vertebrates have more Hox gene clusters than fruit flies.
- Explain, with examples, how the phenotypes of loss-of-function and gain-of-function mutations in Hox genes differ.