ences, but even this pursuit will benefit from the context of knowledge of the processes shared with other organisms. For example, unique mammalian processes, such as extra-embryonic tissue formation or more extensive forebrain development, are still expected to entail many of the same signal transduction pathways and genetic regulatory circuits as used elsewhere in development.

The Evolutionary Perspective

In light of the availability of base sequences for a variety of kinds of genes in a variety of organisms, the place of metazoa (the multicellular animals) among the kingdoms of living organisms has been recently re-evaluated. It now appears that animals share a common ancestor more closely with plants (especially fungi) than with protozoa such as ciliates or amoebae. These three multicellular kingdoms arose from a common eukaryotic ancestor (probably single celled) perhaps 1.2 billion years ago, whereas eukaryotic single cells go back 2.2 to 2.7 billion years and prokaryotic life goes back perhaps 3.5 billion years (Feng et al. 1997; Pace 1997). The conservation of basic biochemical, genetic, and cell biological functions has been surprisingly extensive in that long lineage. At least 3 billion years ago, ancient prokaryotes originated the processes of replication, transcription, translation, energy metabolism, and biosynthesis, and those processes have been carried forward to this day with little change in all life forms, including animals. The comparisons of the whole genomes of bacteria, yeast, and now the nematode, C. elegans, show clearly the conservation of the protein-coding sequences of genes. At least 2 billion years ago, single-celled eukaryotes originated the basic cell biological processes of mitosis, meiosis, a cdk-cyclin-based cell cycle, an actin-based cytoskeleton and myosin-based movements, a tubulin-based cytoskeleton and kinesin-dynein-based movements, membrane-trafficking, and membrane-bounded organelles. These processes and structures have been carried forward by the single-celled eukaryotes and animals with little change to this day.

In light of this conservation of ancient processes, what have metazoa added in the past 1.2 billion years? Their innovations include abundant cell-cell signaling, extracellular matrix, cell junctions, and a wide range of responses to intercellular signals based on complex genetic regulatory circuits and protein phosphorylation. The C. elegans genome shows that, compared with yeast, metazoa have greatly expanded the number of genes encoding proteins of signal transduction, the cytoskeleton, and transcriptional regulation and have greatly increased the size and complexity of the cis-regulatory regions of genes. Metazoa seem to have evolved in a regulatory or informational direction, that of determining the time, location, and circumstances within a multicellular population for activating and inhibiting the many conserved biochemical and cell biological processes brought forward from their single-celled ancestors. All these ancient processes have been made contingent on cell-cell signaling.



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