The Regulatory Genome: Gene Regulatory Networks in Development and Evolution
By Eric H. Davidson
All living organisms deploy similar evolutionarily conserved mechanisms to generate energy, replicate their genomes, use genetic information and synthesize basic building-blocks for their cells. Yet the myriad shapes and forms of both plants and animals are overwhelming in their variety and extremes. What is even more amazing is that most plants and animals start their life as a single diploid cell (a zygote) created by the union of a sperm and an egg. How these simple cells give rise to such complex creatures with diverse body shapes is a major preoccupation of developmental biologists.
Developmental biology mainly deals with the processes and regulatory mechanisms that guide the conversion of a unicellular zygote into a multicellular organism. The progression of body shapes and forms over evolutionary time is another fascinating topic that occupies students of development and evolution alike. As Eric Davidson convincingly argues in his book The Regulatory Genome, animal (and plant) development is driven by a “dynamic progression of regulatory states, defined by the presence and state of activity in the cell nuclei of particular sets of DNA recognizing regulatory proteins (transcription factors), which determine gene expression”. An equally important contributor to development is the “genomic apparatus that encodes the interpretation of these regulatory states”. Over evolutionary time, “the alteration of body plans is caused by changes in the organization of this core genomic code for developmental gene regulation”. The genomic code that dictates animal development and the genetic apparatus that implements it are the main topics of the book.
Initially a descriptive science, developmental biology has benefited hugely from the revolution in molecular biology of the past 30 years. Indeed, The Regulatory Genome is entirely different from Davidson's first book, Gene Activity in Early Development (Academic Press, 1968), which preceded molecular cloning and rapid DNA sequencing. However, even in the earlier book, which I remember reading as a graduate student, Davidson championed a quantitative, biochemical and mechanistic approach to the study of developmental biology. His latest book goes many steps beyond that, explaining the basic processes of development and evolution in terms of information processing and computational logic. The Regulatory Genome incorporates and integrates many recent advances in understanding gene regulation and genomic organization in a quest for a unified model to explain animal development and the evolution of body shapes and forms.
As a scientist interested in gene regulation and signal transduction, I think the most important and valuable message conveyed by the book is the central role of the DNA elements, the cis-regulatory elements and control units, in both development and evolution. Most molecular biologists are occupied as I am with the study of regulatory proteins, either transcription factors or signal transducers that eventually modulate transcription-factor activity. So it is a refreshing and sobering realization that the cis-regulatory elements — the genomic DNA units recognized by sequence-specific transcription factors — occupy a more central role in the design of the genetic circuits and networks that control developmental processes and mediate evolutionary diversification than the transcription factors themselves. This makes sense because, in most cases, sequence-specific transcription factors or the signalling proteins that modulate their activity are highly conserved among organisms with very different shapes and forms. Yet the constellations of cis-regulatory elements, which together make up the cis-regulatory control units that dictate the time, place and magnitude of gene expression, are more diverse and seem to evolve more rapidly than the transcription factors that recognize them. Furthermore, such control units also dictate the expression patterns of transcription factors and signalling proteins in time and space, and thereby determine the exact patterns and repertoires of developmental gene expression.
In general, Davidson does an excellent job of reducing the complexity of different developmental pathways and modes of embryonic development in diverse animal phyla to a set of simplified and logical concepts and principles. He provides excellent illustrations and experimental examples derived from several model organisms: nematode worms, fruitflies, sea urchins, tunicates and vertebrates of different sorts. What is especially attractive about the book are the regulatory networks drawn as simple wiring and computational diagrams. These go a long way towards explaining the basic regulatory logic and engineering principles of some of the most complex biological phenomena: animal development and the evolution of body forms.
This book should be read by all biologists who want to understand how development and evolution take place and what governs the workings of genomes. I also recommend it to computer scientists and engineers who are interested in the budding field of computational biology, as reading it does not require an extensive background in developmental biology.