Eukaryotic DNA and Development

DNA information - The life of the eukaryotic organism is carefully programmed in its DNA, but eukaryotic DNA is more than simply the recipes for proteins and special nucleic acids. Special signals hidden within the genes determine how transcripts will be cut and spliced, where gene products will go, and even how long they will last. In addition, a vast amount of information, usually coded in the sequences surrounding certain genes, specifies when, either in the course of development or in response to environmental stresses, certain genes are to be transcribed.

Elaborate programming - At a higher level, further genetic instructions coordinating these transcriptional instructions must exist, because the development of an organism requires the programmed differentiation of some cells, the proliferation of certain tissues, and the death of selected cells.

Developmental changes - Much of what is known about development comes from study of the fruit fly Drosophila melanogaster. As the larva of this insect develops, groups of cells are set apart as disklike structures called imaginal disks (Figure 28.45). These groups of cells will form specific parts of the adult fly. As the larva metamorphoses, larval cells are destroyed by autolysis, and each imaginal disk develops into a different portion of the adult.

Homeotic gene control - Geneticists working with Drosophila have long recognized classes of homeotic mutations-mutations that scramble the whole developmental pattern in defined ways. One, called the Antennapedia mutation, causes perfectly formed legs to grow in the places near the eye where antennae are normally formed. Another group, called bithorax mutations, leads to abnormal development of thoracic segments, producing, for example, extra pairs of wings. Large clusters of homeotic genes control these developmental processes and are the sites of homeotic mutations. A common sequence element, called the homeo box, has about 180 bp and is repeated many times in these gene clusters. The homeo box codes for a 60-residue polypeptide sequence called the homeo domain. Proteins containing this domain are nuclear, DNA-binding proteins of the helix--loop--helix class (see here). It seems likely that each acts as a regulator of transcription for a coordinated group of proteins.

Other Homeo Boxes - The homeo box is found in many other organisms, including amphibians and mammals, with sequences remarkably conserved over this phylogenetic range.