Sequence changes in structural genes (those that encode functional proteins) are responsible for most phenotypic evolution in multicellular organisms. In other words, conventional thought was that protein evolution was at the heart of organismal evolution. Although genetic mechanisms for the regulation of protein-coding genes in bacteria had been identified by Francois Jacob and Jacques Monod in 1961 (a feat for which they later shared a Nobel Prize), the notion that gene regulation might be broadly important in the evolution of multicellular life had not yet percolated widely in the scientific literature for eukaryotes.
gene regulation; molecular genetic model
Sequence changes in structural genes (those that encode functional proteins) are responsible for most phenotypic evolution in multicellular organisms. In other words, conventional thought was that protein evolution was at the heart of organismal evolution. Although genetic mechanisms for the regulation of protein-coding genes in bacteria had been identified by Francois Jacob and Jacques Monod in 1961 (a feat for which they later shared a Nobel Prize), the notion that gene regulation might be broadly important in the evolution of multicellular life had not yet percolated widely in the scientific literature for eukaryotes.
Gene regulation instead plays the major role in phenotypic evolution. Both with respect to the ontogenetic differentiation of body parts within an individual and the phylogenetic differentiation of body plans across diverse forms of life, changes in genetic regulation (how structural genes are switched on or off, or rheostated) assume paramount importance during the evolutionary process.
In 1969, geneticists Roy Britten and Eric Davidson proposed a remarkable molecular model for how such gene regulation might transpire in eukaryotes. In their conceptual construct, the authors envisioned batteries of producer loci (protein-coding or other housekeeping genes) being coordinately regulated by activator RNA molecules synthesized by integrator genes whose effect was to induce or repress joint transcription from multiple producer genes in response to environmental stimuli (such as hormones) acting on particular sensor genes. The model remains worthy of study today, not because it has proved to be correct in all its details (it has not), but because it offers a prime example of avant-garde thinking in evolutionary genomics. Today, the study of gene regulation remains one of the hottest topics in evolutionary biology (ENCODE Project Consortium, 2012), with diverse regulatory mechanisms routinely illuminated at transcriptional, translational, and post-translational levels (see Chapter 63).
This is an example of a paradigm shift that was gradual in the making. During the 1950s and 1960s, evidence slowly accumulated from a wide variety of sources suggesting the many ways in which gene expression might be regulated, both during ontogeny and across the course of evolutionary time. However, Britten and Davidson’s landmark paper in 1969 helped to crystallize many of these emerging ideas. Their classic paper highlighted the potential significance of gene regulation, and also formulated an innovative hypothesis for how such processes might transpire in a mechanistic sense. Their molecular genetic model, which incorporated recent discoveries on the ubiquity of repetitive DNA in eukaryotic genomes (see Chapter 39), was conceptually far ahead of its time. This paradigm shift also gets a high score because nearly all evolutionary geneticists now fully accept the idea that changes in the regulatory apparatus of eukaryotic genomes are central to much of adaptive evolution.
1. Jacob F, Monod J. Genetic regulatory mechanisms in the synthesis of proteins. J Mol Biol. 1961;3:318–356.
2. Britten RJ, Davidson EH. Gene regulation for higher cells: a theory. Science. 1969;165:349–357.
3. Raff RA, Kaufman TC. Embryos, Genes, and Evolution: The Developmental Genetic Basis of Evolutionary Change New York, NY: Macmillan; 1983.
4. Carroll SB, Grenier JK, Weatherbee SD. From DNA to Diversity: Molecular Genetics and the Evolution of Animal Design London, UK: Blackwell; 2001.
5. ENCODE Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57–74.