2) Hox Genes and Evo-Devo (by Rey J. Rosa Morales)

Biologists dating back to Geoffroy Saint-Hilaire (1772-1844), Karl Ernst von Baer (1792- 1876), and Darwin himself were fascinated by the patterns of similarity and divergence in development among species. However until quite recently, the fields of evolutionary biology and developmental biology preceded along mostly separate parts, with seemingly distinct research programs and methodologies. In the past three decades, however, burgeoning information about the genetic mechanisms of morphogenesis in model organisms, as well as the molecular genetic techniques developed to obtain that information, have been integrated with many strands of evolutionary research to form the highly interdisciplinary field now known as Evolutionary Developmental Biology EDB.

Figure 1. A) Wild-type D. melanoganster 

with a single pair of wings and a pair of 

winglike structure, halteres. B) A mutant 

fly was experimentally produce by combining 

several mutations in the regulatory region

of the Ultrabithorax (Ubx) gene. The third

thoracic segment has been transfonned, 

bearing wings instead of  haltares. 

(Photo by E.B. Lewis).  

The discovery and characterization of the Hox cluster of homeobox genes in animals in the 1970 and 1980 marks the dawn of modern EDB. The Hox genes are the best known class of homeotic selector genes, which control the patterning of specific body structures. Hox genes control the identity of segments along the anterior-posterior body axis of all metazoans. Mutations in the Hox genes often cause transformations of one type of segment into another. In Drosophila melanoganster for example, a mutation of the Ultrabithorax (Ubx) gene transforms the third thoracic segment (T3), which normally bears the tiny halteres (the Drosophila homologue of the hindwing of four-winged insects), into a second thoracic segment (T2), which bears  wings (Figure 1 a, b). A  mutation in another Hox gene, Antennapedia (Antp), causes the misexpression of Antp protein in the cells that normally give rise to the antennae, resulting in the replacement of antennae with legs  (Figure 2). Antp is normally expressed only in the second thoracic segment (TI), where it controls the development of T2-specific body structures, including legs.

Figure 2. A) Frontal view of the head of a wild-type Drosophila melanogaster, showing normal
antennae and mouthparts. B) Head  of a fly carrying Antennapedia mutation, which converts antennae into legs. (Photo by F.R. Turner).

     In  Drosophila, the Hox genes occur in two complexes (clusters) of genes on chromosome 3, termed the Antennapedia complex and the bithorax complex. The pioneering genetic work on the bithorax complex was done between the 1940s and the 1970s by E. B. Lewis, and that on the Antennapedia complex in the 1970s and 1980s by Thomas Kaufman and his colleagues. These investigators found that the genes in both complexes control the anterior-posterior identity of segments corresponding to their order on the chromosome  (Figure 3).  They also discovered that the eight Drosophila Hox genes are members of a single gene family, and that the proteins they encode share a particular amino acid sequence that binds DNA, subsequently named the homeobox (in the gene) or the homeodamain (in the protein). This finding supported Lewis's idea, proposed in the 1960s, that the Hox genes regulate the transcription of other genes. Other researchers were stunned to discover that all other animal phyla also possess a set of Hox genes. These genes have homeodomain sequences similar to those of their homologues in Drosophila and have the same gene order and orientation as in Drosophila (except that they form a single gene complex in most animals). Mammals have four Hox gene complexes (denoted Hoxn, Hoxb, Hoxc, and Hoxd) in different parts of the genome, and a total of 13 different Hox genes (as opposed to only 8 in Drosophila), although not all of the complexes have all 13 members (Figure 4).

             Figure 3                                        Figure 4

Figure 3. Hox gene expression in Drosophila. In the center is a map of the genes of the Antennapedia and bithorax complexes, with their functional domains shown in color (© 2008 Sinauer Associates Sadava, D. et al. Life: The Science of Biology, 8th ed.)
 

Figure 4. (right panel) Probable evolution of the metazoan Hox gene complex. Vertical white lines delineate currently  accepted groups of orthologous Hox genes. Important gene duplication events are indicated by the labeled tick marks (Image from the book, Evolution 2009).



References:

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