The End of Gene Control

As the 20th century draws to a close, biologists triumphantly announce the beginning of the end of the project to sequence the human genome. Metaphoric hyperbole runs rampant as we speak of "reading the book of life" and of "unraveling the essence of what it means to be human". But less noticed is the fact that developmental biologists who study the role of genes in development are busily dethroning the gene.

When I was a young embryologist I lectured about genes in development. Following the dogma of the time, I told my students that there were two groups of genes. First, there were housekeeping genes — those responsible for the mundane daily functions of the cell — the feminine duties of maintenance. These genes supposedly kept the machinery running smoothly — respiration and waste disposal went on quietly and demurely. But the really important genes were the development genes — those masculine entities that pioneered new territory and wrought new form from undifferentiated plasm. The goal of any self-respecting developmental geneticist was to find those special genes for development and thus unravel the mystery of how genes control the formation of new organisms.

The successes have been many and profound. Developmental biologists have uncovered myriad genes involved in embryo formation. They have found an amazing continuity of genetic structure and function across the phyla. We now understand in fabulous detail the function of many genes in development. But something funny happened on the way to the genetic forum. The distinction between housekeeping genes and development genes has become increasingly hard to maintain. Some development genes fall into the category of transcription regulators, as might be expected for genes that control genetic expression. But many turn out to be involved in cell communication and signaling. What is more these genes don't control development. In a real sense development controls the genes. The same genetic read-out can have a vastly different outcome depending upon when during development and in which cell the protein is produced. Indeed, most development genes seem to act at multiple times during development and in many tissue and cell types. The same gene can play a key role in quite a variety of developmental events.

The important story is that the search for genes that control development has shown us that our initial idea that genes control processes within an organism is wrong. Instead genes are one set of actors within a developmental system. The system itself contains all of the pre-existing contents of the cell, organ or organism. These include thousands of gene products, other chemicals such as ions, lipids, carbohydrates and more, all organized and compartmentalized in a highly-stru ctured physical setting (the cell and its substructures, the organ and its tissues, the organism and its organ systems). From before the turn of the century embryologists debated whether the cytoplasm controlled the nucleus or vice versa. What the last decade of research on genes in development reveals is that both things are simultaneously true — the system and its history control development. Genes are but one of many crucial components of the process.