Evolution of Gene Expression

by

David Stern

• LAST REVIEWED: 27 October 2016
• LAST MODIFIED: 27 October 2016
• DOI: 10.1093/obo/9780199941728-0085

Introduction

Gene expression is the spatial and temporal pattern of a gene product, such as mRNA or protein. Since the early 1960s, multiple scientists have argued that biological diversity results mainly from changes in gene expression. With the advent of molecular techniques, many studies have demonstrated evolutionary changes in gene expression, and some of these studies have provided causal links between changes in gene expression and evolutionary differences in morphology and physiology. It is now widely believed that the evolution of gene expression is a major source of phenotypic diversity. DNA located mainly outside of protein-coding regions determines gene expression. Often, this regulatory DNA is organized in apparently modular regions called cis-regulatory elements or enhancers. Enhancers bind transcription factors that can either activate or repress gene expression. The expression pattern driven by modular enhancers reflects the combined activity of the activators and repressors. Because transcription factor binding sites are encoded as DNA sequences of approximately 6 to 12 bp, individual binding sites can evolve quickly through single-nucleotide changes and small insertions and deletions. Many enhancers evolve quickly through gain and loss of binding sites while retaining a conserved function. Against this background of extensive turnover, some mutations generate novel enhancer functions, which contribute to biological diversity. Methodological advances have underpinned most of the major discoveries in the study of the evolution of gene expression. These advances have included the following, in rough chronological order: the detection of allozyme variation, the use of protein and DNA sequencing, development of molecular biology techniques that have allowed increasingly sophisticated methods of in vitro gene splicing, development of in situ hybridization against mRNA and proteins, exploitation of cross-reactive antibodies, development of transgenic technologies, whole-genome sequencing and related genomics methods, and site-specific homologous recombination, most recently facilitated by TALENs and CRISPR. In the future, as a direct result of recent technology breakthroughs and the introduction of new techniques, increasingly rigorous and comprehensive studies of gene expression evolution in a wide variety of organisms may be done.

General Overviews

Many reviews and books discuss the evolution of gene expression. Most were written for a specialist audience, but some were written for a more general audience. Emphasized in this article are relatively recent reviews and books, many of which review the history of the field and include key earlier reviews. Important reviews include those by Carroll 1995 on the potential role of homeotic genes in evolution, Akam 1998 on the clarification of how Hox genes could evolve through small steps, Stern 2000 on how the pleiotropic effects of most mutations will favor cis-regulatory evolution, and Villar, et al. 2014 on genome-wide transcription factor occupancy studies. Important books include Gerhart and Kirschner 1997 with a review of evolution and development and a proposal that developmental systems may have evolved to be evolvable, Wilkins 2002 with a balanced and thorough review of the evolution of developmental networks, Davidson 2006 on the precise deconstruction of regulatory networks and how they evolve, and Stern 2010 in an attempt to merge developmental biology with a population genetics–based understanding of evolution.

• Akam, M. 1998. Hox genes, homeosis and the evolution of segment identity: No need for hopeless monsters. International Journal of Developmental Biology 42.3: 445–451.

  In this important review, Akam explored how the cis-regulatory architecture of Hox genes likely makes it possible for Hox genes to evolve through mutations of small effect. Thus, evolution of body plans through changes in Hox gene expression patterns is likely to be consistent with the contemporary understanding of evolutionary change.

• Carroll, S. B. 1995. Homeotic genes and the evolution of arthropods and chordates. Nature 376:479–485.

  DOI: 10.1038/376479a0

  Reviews evidence for the contribution of changes in homeotic gene function, copy number, and regulation in phenotypic evolution. Includes what may be the first explicit suggestion that specific regulatory mutations probably contribute disproportionately to phenotypic evolution because they limit pleiotropic consequences of mutational changes.

• Davidson, E. H. 2006. The regulatory genome: Gene regulatory networks in development and evolution. Burlington, MA: Academic Press.

  This book reviews in some detail the function of cis-regulatory regions in development and the way in which these regulatory regions contribute to developmental evolution.

• Gerhart, J., and M. Kirschner. 1997. Cells, embryos, and evolution. Malden, MA: Blackwell Science.

  This early review of evolution and development made the controversial argument that developmental systems have evolved to be evolvable.

• Stern, D. L. 2000. Perspective: Evolutionary developmental biology and the problem of variation. Evolution 54.4: 1079–1091.

  This review addressed how regulatory evolution makes developmental evolution compatible with classical insights from evolutionary biology and population genetics. In particular, the case is made that small changes in cis-regulatory regions are likely to make major contributions to evolution because they have limited pleiotropic effects.

• Stern, D. L. 2010. Evolution, development, & the predictable genome. Greenwood Village, CO: Roberts.

  This book synthesizes insights from evolutionary developmental biology and population genetics to explore why regulatory evolution is so common and how this explains the repeated evolution of the same genes causing phenotypic convergence.

• Villar, D., P. Flicek, and D. T.Odom. 2014. Evolution of transcription factor binding in metazoans—Mechanisms and functional implications. Nature Reviews Genetics 15:221–233.

  DOI: 10.1038/nrg3481

  An excellent review of genome-wide transcription factor occupancy data in various species and the evolutionary implications.

• Wilkins, A. S. 2002. The evolution of developmental pathways. Sunderland, MA: Sinauer.

  This erudite and historically grounded book examines the role of gene regulatory evolution within the larger context of evolving developmental pathways.