In 1969, Roy J. Britten and Eric H. Davidson published Gene Regulation for Higher Cells: A Theory, in Science. A Theory proposes a minimal model of gene regulation, in which various types of genes interact to control the differentiation of cells through differential gene expression. Britten worked at the Carnegie Institute of Washington in Washington, D.C., while Davidson worked at the California Institute of Technology in Pasadena, California. Their paper was an early theoretical and mechanistic description of gene regulation in higher organisms.
Francois Jacob studied in bacteria and bacteriophages at the Institut Pasteur in Paris, France, in the second half of the twentieth century. In 1965, Jacob won the Nobel Prize in Physiology or Medicine with Andre M. Lwoff and Jacques L. Monod for their work on the genetic control of enzyme synthesis. Jacob studied how genes control and regulate metabolic enzymes in the bacterium Escherichia coli (E. coli) and in lysogenic bacterial systems. He contributed to theories of transcriptional gene regulation, the operon model, and the distinction between structural and regulatory genes. Jacob also introduced the concept of bricolage (tinkering) in evolutionary biology.
In his essay Evolution and Tinkering, published in Science in 1977, Francois Jacob argued that a common analogy between the process of evolution by natural selection and the methods of engineering is problematic. Instead, he proposed to describe the process of evolution with the concept of bricolage (tinkering). In this essay, Jacob did not deny the importance of the mechanism of natural selection in shaping complex adaptations. Instead, he maintained that the cumulative effects of history on the evolution of life, made evident by molecular data, provides an alternative account of the patterns depicting the history of life on earth. Jacob's essay contributed to genetic research in the late twentieth century that emphasized certain types of topics in evolutionary and developmental biology, such as genetic regulation, gene duplication events, and the genetic program of embryonic development. It also proposed why, in future research, biologists should expect to discover an underlying similarity in the molecular structure of genomes, and that they should expect to find many imperfections in evolutionary history despite the influence of natural selection.
L'Institut Pasteur (The Pasteur Institute) is a non-profit private research institution founded by Louis Pasteur on 4 June 1887 in Paris, France. The Institute's research focuses on the study of infectious diseases, micro-organisms, viruses, and vaccines. As of 2014, ten scientists have received Nobel Prizes in physiology or medicine for the research they have done at the Pasteur Institute. Contrary to the way genetics was studied in US research universities during the mid-twentieth century, the genetic research conducted at the Pasteur Institute at the same time did not rest on a conceptual separation between embryology and evolution. According to historian Michel Morange from the Ecole Normale Superieure in Paris, France, this difference enabled Pasteurian scientists to develop the concepts of regulatory genes and of developmental genes.
Lysogenic bacteria, or virus-infected bacteria, were the primary experimental models used by scientists working in the laboratories of the Pasteur Institute in Paris, France, during the 1950s and 1960s. Historians of science have noted that the use of lysogenic bacteria as a model in microbiological research influenced the scientific achievements of the Pasteur Institute's scientists. Francois Jacob and Jacques Monod used lysogenic bacteria to develop their operon model of gene regulation, to investigate the cellular regulatory mechanisms of the lysogenic life cycle, and to infer the process of cellular differentiation in the development of more complex eukaryotes.
Roy John Britten studied DNA sequences in the US in the second half of the twentieth century, and he helped discover repetitive elements in DNA sequences. Additionally, Britten helped propose models and concepts of gene regulatory networks. Britten studied the organization of repetitive elements and, analyzing data from the Human Genome Project, he found that the repetitive elements in DNA segments do not code for proteins, enzymes, or cellular parts. Britten hypothesized that repetitive elements helped cause cells to differentiate into more specific cell kinds among different organisms.
The hedgehog signaling pathway is a mechanism that regulates cell growth and differentiation during embryonic development, called embryogenesis, in animals. The hedgehog signaling pathway works both between cells and within individual cells.
Apoptosis, or programmed cell death, is a mechanism in embryonic development that occurs naturally in organisms. Apoptosis is a different process from cell necrosis, which is uncontrolled cell death usually after infection or specific trauma. As cells rapidly proliferate during development, some of them undergo apoptosis, which is necessary for many stages in development, including neural development, reduction in egg cells (oocytes) at birth, as well as the shaping of fingers and vestigial organs in humans and other animals. Sydney Brenner, H. Robert Horvitz, and John E. Sulston received the Nobel Prize in Physiology or Medicine in 2002 for their work on the genetic regulation of organ development and programmed cell death. Research on cell lineages before and after embryonic development may lead to new ways to reduce or promote cell death, which can be important in preventing diseases such as Alzheimer's or cancer.
In 2003, molecular biology and genetics researchers Coleen T. Murphy, Steven A. McCarroll, Cornelia I. Bargmann, Andrew Fraser, Ravi S. Kamath, Julie Ahringer, Hao Li, and Cynthia Kenyon conducted an experiment that investigated the cellular aging in, Caenorhabditis elegans (C. elegans) nematodes. The researchers investigated the interactions between the transcription factor DAF-16 and the genes that regulate the production of an insulin-like growth factor 1 (IGF-1-like) protein related to the development, reproduction, and aging in C. elegans. Transcription factors, like DAF-16, are proteins that regulate the transcription of deoxyribonucleic acid (DNA) into messenger ribonucleic acid (mRNA), which later determines which proteins the cell produces. The research team's experiment suggested that an increase in the activity of the DAF-16 protein decreases the transcription of the genes that regulate the production of IGF-1-like proteins, increasing lifespan in nematodes. The team published their results in the article 'Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans' in Nature in June 2003. By comparing the regulation of gene expression in C. elegans with similar genes and pathways in humans, Murphy's research team sought to better understand cellular function and aging in humans.
In 2002 Eric Davidson and his research team published 'A Genomic Regulatory Network for Development' in Science. The authors present the first experimental verification and systemic description of a gene regulatory network. This publication represents the culmination of greater than thirty years of work on gene regulation that began in 1969 with 'A Gene Regulatory Network for Development: A Theory' by Roy Britten and Davidson. The modeling of a large number of interactions in a gene network had not been achieved before. Furthermore, this model revealed behaviors of the gene networks that could only be observed at the levels of biological organization above that of the gene.