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Mulitcellular Organisms

Homeobox Genes

Multicellular organism development involves many processes as illustrated in the simple case of slime moulds. These include chemical signal, chemical gradient, cellular adhesion, anterior-posterior polarity, pattern formation, cell movement, and cell differentiation. Multicellular organisms have all these functions achieved under the direction of the Homeobox (or Hox) genes3, which manifests itself at an early stage of embryonic development and determines the shape of the body. Humans, worms and flies don't look very similar and they do not go through the same developmental stages. Yet the Hox genes that control their body shape and organization are relan early stage of embryonic development and determines the shape of ated in sequence. The corresponding homeobox protein controls the activities of other genes. Mutation in Hox gene usually cause abnormal growth, e.g., a leg on the head.

A region of 180 nucleotide sequence coded for 60 amino acids4 in the homeobox protein is embedded in the Hox genes. The rest of the sequence may be very different, but this 60 amino acid piece called homeodomain is crucial for its function. Figure 10-07a depicts the Hox genes for the development of various regions (coded in different colours) in the fruit fly (Drosphila), mouse, and human. Different kinds of creatures have
Hox Genes HomeoDomain HoxEmbryo different numbers of Hox genes. The lowly anemone have 5 for specifying the front and back ends. Flies and other insects have 8. Mice and other mammals have 4 sets (labeled as HoxA, B, C, D) altogether through duplication totaling 38. The Hox genes are clustered in the chromosome in the exact order as shown. They are expressed in the same order of this spatial sequence, which is also the temporal order of expression.

Figure 10-07a Hox Genes[view large image]

Figure 10-07b Homeodomain
[view large image]

Figure 10-08 Early Development

Figure 10-07b presents a magnified view of the homeodo-main within the homeobox protein.
Each letter in the consensus string represents an amino acid. Deviations from that consensus are shown for some of the homeobox proteins in Drosphila (upper row) and mouse (lower row). Figure 10-08 shows the gradually diversified development of the embryo across species from fruit fly to fish, salamander, chicken, rabbit, and human. It reveals that despite the differences in the final appearance of the animals, they use closely related genes to specify parts of the body along the anterior-posterior (head-tail) axis in the very early stage. It is believed that the developments of limbs and other specialized parts are controlled by retinoic acid (a version of vitamin A) gradient as the substance diffuses from a source. The hox genes respond differently according to the concentration of the retinoic acid.

The importance of chemical gradient in embryonic development is supported by mathematical models generated from the Turing equation which describes the diffusion process involving activator molecules (to activate a cellular process) and inhibitors (that counter the effects of the activator). The mathematical models are able to reproduce realistically many complicated patterns in animals.

Phylotypic Stage As shown in Figure 10-08, the common feature of animals appeared quite early in development and that specialized features only appeared later. For unknown reason, it seems that in any group of related animals, such as vertebrates, there is a stage in development which is common to all members of the group. This stage is called the phylotypic stage (Figure 10-09a). For vertebrates, it immediately follows gastrulation (about 20 days after fertilization for human) when the main body axis with a very primitive head, and the first few segmented somites, can be seen. Before and after the phyloptypic stage the developmental pathway may be quite different. Thus, ontogeny (development of an individual to maturity) repeats some embryonic features of ancestors in their embryonic development; it does not represent the evolutionary history of an animal as claimed by the German biologist Ernst Haeckel's biogenetic law, which states that "an animal's embryonic development recapitulates its evolution".

Figure 10-09a Phylotypic Stage [view large image]

BTW, the somite is one of a series of paired blocks of cells that develop along the back of a vertebrate embryo giving rise to the vertebral column and most of the skeletal muscles.

Developmental Hourgalss Two papers in the December 9, 2010 issue of Nature have quantified the rather subjective definition of phylotypic stage relying on anatomical shapes. The diagram in the left of Figure 10-09b shows the minimum gene-expression divergence at period identical to the minimal anatomical divergence between species as shown by the orange band. The diagram in the middle of Figure 10-09b present the results from another research, which found the expression of ancient genes right on the phylotypic stage. These genes produce segmentation and pharyngula (producing features such as notochord, nerve cord, post-anal tail, etc.), i.e., the

Figure 10-09b Developmental Hourglass [view large image]

basic body plan is laid down at this stage. This kind of curve in the diagrams is sometimes referred to as developmental (or genomic) hourglass.

Syndactyly Evolutionary throwback (atavism or backward evolution) may occur if anything goes awry during embryonic development. Early embryos of many species develop ancestral features. Snake embryos, for example, sprout hind limb buds, as do whale and dolphin embryos, and human embryos have a tail bud. These features usually disappear in later development. But if anything goes wrong in the process, perhaps through a mutation, the ancestral feature may be retained such as the hind limb in the snake. There are many forms of atavism in human including large canines, extra breasts or nipples, polydactyly (extra fingers or toes), and syndactyly (webbed fingers or toes, Figure 10-09c).

Figure 10-09c Syndactyly
[view large image]

3A gene is defined to be a section of DNA that transcribes a protein. The gene expression (transcription) is initiateed by binding the transcription factor (such as the homeodomain) to the beginning section of the gene called the promoter.

4Protein is produced from DNA via the transcription/translation process. The base (nucleotide) Thymine (T) becomes Uracil (U) in the transcription from DNA to RNA. Three bases translate into one amino acid according to the genetic code. The amino acids link together to form a protein.

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