standing an organism’s development and to identifying components of developmental processes.

Synergy with Research Advances in Other Areas

Meanwhile, other researchers worldwide made advances in biochemistry, molecular biology, cell biology, and genetics. They learned an enormous amount about the function of proteins in replication, transcription, translation, secretion, uptake, membrane trafficking, cell motility, cell division, the cell cycle, cell adhesion, and apoptosis (programmed cell death), to mention but a few of the cellular processes. Researchers improved the methods to isolate genes, sequence them, manipulate sequences, make transcripts in vitro, detect messenger (m)RNAs in cells by in situ hybridization, translate RNAs to proteins in vitro, and make antibodies to proteins. In situ hybridization, which graphically revealed the time and place of expression of specific genes in the embryo, was to prove particularly important for connecting the new molecular analysis to the older developmental anatomy. Much of the work was initially done with single-celled organisms: bacteria, yeast, or animal cells in culture. Some insights and techniques came from the study of cancer cells in the search for oncogenes.

In the course of that work, many of the processes, protein functions, and protein sequences were found to be strongly conserved among organisms as diverse as yeast and humans or even bacteria and humans. Various proteins of different organisms, and also within the same organism, shared “sequence motifs” by which the protein could be recognized as a member of a protein family with a particular function and descended from a common sequence ancestor. Newly discovered proteins could be assigned a function from just their possession of a particular motif. As more motifs were found, it will be easier to categorize newly discovered proteins. For example, receptor tyrosine kinases were recognizable by their transmembrane hydrophobic motifs and adenosine triphosphate (ATP)-binding domains. G-protein-linked receptors could be distinguished by a seven-pass (serpentine) transmembrane motif. Transcription factors could be recognized by the sequence motifs of their deoxyribnucleic acid (DNA) binding domains (e.g., zinc finger, basic helix-loop-helix, homeodomain, or leucine zipper domains). Of the recently sequenced genomes of yeast and C. elegans, for example, about 40% of the open reading frames (ORFs) are recognizable by known motifs (Chervitz et al. 1998). Function can be assigned, at least preliminarily, to the products of those genes. Plans are afoot to define the function of the missing ORFs of yeast and make the functions of all proteins assignable from sequence. At the same time, there are plans to identify a large number of protein-binding sequences in the regulatory regions of genes to be able to predict better the conditions of expression of genes. These plans are among the aims of “functional genomics,” as described in Chapter 5. All the information on sequences, motifs, and function is stored in databases available



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