What are Hox genes and what do they have to do with linking a fruit fly to you?

Question

What are Hox genes and what do they have to do with linking a fruit fly to you? How did experiments with mice contribute to our understanding of animal development?

some links :

http://www.nature.com/scitable/topicpage/hox-genes-in-development-the-hox-code-41402

Gregor Mendel and the Principles of Inheritance – Miko (Nature Ed)

http://www.nature.com/scitable/topicpage/gregor-mendel-and-the-principles-of-inheritance-593

Mendelian Genetics: Patterns of Inheritance and Single-Gene Disorders – Chial (Nature Ed)

http://www.nature.com/scitable/topicpage/mendelian-genetics-patterns-of-inheritance-and-single-966

Phenotypic Range of Gene Expression: Environmental Influence – Lobo & Shaw (Nature Ed

Explanation / Answer

Hox Genes

Hox proteins are a group of homeodomain-containing transcription factors that are renowned for their roles in patterning animal body plans and for their remarkably deep evolutionary conservation. Homeodomain proteins are defined by the presence of a highly conserved DNA-binding region known as the homeodomain and are encoded by Homeobox genes. In general, homeobox genes are a large family of similar genes and can be divided into 11 different gene classes in animals, and the Hox genes belong to the ANTP class. This class of genes also includes the closely related ParaHox genes, NK genes, and various others.

Hox genes were originally discovered in Drosophila and functional studies in the fly showed that these genes play a critical role in establishing segmental identity along the antero-posterior axis.

Homeobox (Hox) genes were discovered following the observation of two striking mutations in the fruit fly, Drosophila melanogaster. In the antennapedia mutation the antennae are changed into legs, whereas in the bithorax mutation, the haltere (a balancing organ on the third thoracic segment) is transformed into part of a wing. These changes were described as homeotic transformations from the Greek word homeosis, signifying a change of a complete body structure into another.

Homeobox genes are present in the genomes of all animals which have so far been mapped as well as in the genomes of plants and fungi, indicating that the origins are ancient and precede the divergence of these kingdoms. Plants, fungi and unicellular animals do not, however, have clustered homeobox genes.

HOX genes are evolutionarily highly conserved. The HOX proteins which they encode are master regulators of embryonic development and continue to be expressed throughout postnatal life.

Contribution of mice to our understanding of biology

Mouse genetics probably has its roots in China, with what began as a fascination with albinos, coat colour varieties and waltzing mice, eventually leading to the enthusiastic breeding of fancy mice in Victorian Europe. Modern day laboratory mice, in fact, are thought to be direct descendants of only a few of these original fancy stocks. C. C. Little went on to show, for the first time, the genetic basis of the resistance to the growth of transplanted tumors in inbred mice, since some were resistant to the transplantation (Paigen, 2003). This heralded the beginning of mouse genetics.

For decades, these inbred mice have been an invaluable genetic tool in cancer research and immunology. In fact, it was George Snell who developed the concept of congenic mice, where a single locus can be manipulated between strains to reduce complexity, which enabled him to elucidate the function of the H2 histocompatibility loci. The underlying principle for tumour rejection in Little’s transplants was finally revealed to have an immunological basis. This later led to the discovery of the major histocompatibility complex (MHC) in humans and eventually won Snell the Nobel Prize. To date, hundreds of lines of inbred mice have been established and hundreds of spontaneous mutations have been isolated. The collection represents a rich resource of natural genetic diversity and alterations that have provided insights into mammalian biology and human disease. For example, work in mice enabled the discovery of the obese (ob) and diabetic (db) gene products as the satiety hormone leptin and its receptor, respectively.

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