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Homeobox

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A homeobox is a segment of DNA about 180 base pairs long that is found within genes. It bonds with proteins in which it resides in a DNA-binding homeodomain about 60 amino acids long encoded by the homeobox. The protein is a major building block of an organisms genome. Homeobox genes, or genes containing a homeobox, are thus a viable model to interpret or predict, and in manipulation control embryogenesis and phenotype expression of homologous structures that constitute multicellular organisms. [1]

Contents

Discovery

In 1983 Walter Jakob Gehring and his colleagues at the University of Basel, Switzerland observed the homeotic genes in the common fruit fly, or Drosophila melanogaster. Before this unique discovery, it was not thought that the same genetic mechanism, namely homeobox genes, were at play for both invertebrates and vertebrates alike.

Matthew Scott and Amy Weiner were then working with Thomas Kaufman at Indiana University in Bloomington and can also be credited to an extent. Scott said quite succinctly that,

Instead of having to study genes and proteins and molecular events that are very specific to one tissue, or one developmental stage, or one organism, you can take advantage of the special attributes of whatever your experimental system is, and whatever you learn is likely to be very useful in understanding a great many other events in other tissues, stages, and creatures. [2]

Hox Genes

Body directions used by anatomists
Body directions used by anatomists

Hox genes are a subgroup or subset of homeobox genes. Within vertebrates they can be found in gene clusters on chromosomes. They regulate development of the anterior to posterior axis. It is important to note that only genes in the hox cluster should be considered hox genes and the gene name hox is restricted to only hox cluster genes in vertebrates, while the homeobox is the overarching encoder for the homeotic genes to begin with. [3]

Hox Cluster

A hox cluster is a grouping of homeotic genes, called hox genes in vertebrates. Clusters of genes turn on in sequence to determine the overall body pattern from the front to the back, and top to bottom. Genes cascade down like waves rushing ashore which then lay out increasingly localized structures. These structures which ultimately become segments of an organisms body are identified by the homeotic gene which ultimately controls the phenotype expression.

In other words the fate of a given segment is determined by the expression of specific homeotic genes for that segment. [4] [5]

Hox Genes and Evolution

The PNAS journal article entitled, Detection of homeobox genes in development and evolution [6], states the problems and assumptions that arise when the evolutionary path has to be followed. In a section called, Evolutionary Survey of Antp-Class Homeobox Sequences, it states;

The strict evolutionary conservation of homeobox sequences and their chromosomal organization suggests that the number and type of homeobox genes in a particular species, as well as the organization of those genes, may correlate with the level and complexity of their embryonic development. Such a correlation would make the homeobox gene system crucial to the understanding of evolutionary relationships among the metazoans. Genomic DNAs from selected metazoan species, whose presumed relationships are depicted in Fig. 3a (36), were surveyed by PCR with primers HoxA and HoxB. PCR products of the size expected from Antp-class homeobox sequences were observed in all species examined (Fig. 3b), including the hydrozoan Sarsia and the colonial hydroid Hydractinia symbiolongicarpus. To ensure that these products were not artifactual, several clones were characterized for Sarsia. Three sequences related to Antp were observed (Fig. 4). SAoxl and SAox2 are clearly related to the Antp class. SAoxl is most closely related to Hox-1.6 and lab sequences, while SAox2 is more closely related to Hox-2.8 and pb sequences. SAox3 is most likely an Antp-like homeobox sequence, but is relatively diverged and its relationship to known homeobox sequences is unclear. It shares 15 of 25 amino acids with Ubx but also shares 14 of 25 amino acids with several other types of Antp-class sequences (data not shown). We have also observed sequences similar to SAox2 and SAox3 in other cnidarians (41). In addition, the Sarsia sequences show a strong bias for A+T-rich codons, a characteristic observed for other cnidarian genes (H. Bode, personal communication). This bias may account for the previous inability to detect these sequences by more classical techniques (5, 6).

References

  1. The Homeobox Page by Thomas R. Bürglin for Department of Biosciences and Nutrition
  2. The Fruitful Fruit Fly: Discovering the Homeobox by Howard Hughes Medical Institute
  3. The Homeobox Page by Thomas R. Bürglin for Department of Biosciences and Nutrition
  4. The Fruitful Fruit Fly: Discovering the Homeobox by Howard Hughes Medical Institute
  5. The Homeobox Page by Thomas R. Bürglin for Department of Biosciences and Nutrition
  6. Detection of homeobox genes in development and evolution by Michael T. Murtha, James F. Leckman and Frank H. Ruddle. Proceedings of the National Academy of Sciences (PNAS) Vol. 88, pp. 10711-10715, December 1991, Developmental Biology

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