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Comparative studies of gene expression and the evolution of gene regulation

Nature Reviews Genetics volume 13, pages 505–516 (2012)Cite this article

Subjects

Key Points

  • The hypothesis that differences in gene regulation have an important role in speciation and adaptation is more than 40 years old.

  • RNA sequencing (RNA-seq) allows measurement and comparison of gene expression levels across practically any combination of species at an unprecedented resolution.

  • Comparative studies of gene expression levels in all species studied to date provide compelling evidence that most gene regulatory patterns evolve under evolutionary constraint.

  • It is more difficult to infer the action of positive (directional) selection on gene regulation than the action of stabilizing selection, especially in non-model species such as humans and non-human apes, where environmental and genetic effects might be confounded.

  • Inter-species differences in epigenetic markers can probably explain a substantial fraction of gene expression differences between species.

  • Because a broad range of experimental manipulations are possible in model organisms, studies that focus on model species can move beyond simple comparisons of gene expression and offer deep insights into the causal relationship between regulatory changes and phenotypic evolution.

  • Functional studies in model systems can often shed light on the adaptive phenotypes that were affected by regulatory changes between humans and other primates. Some phenotypes, however (for example, the development of language), are inherently difficult to study using model species.

  • It might be possible to use induced pluripotent stem cells derived differentiated cells from humans and non-human primates to test functionally for the outcomes of inter-species differences in gene regulation.

Abstract

The hypothesis that differences in gene regulation have an important role in speciation and adaptation is more than 40 years old. With the advent of new sequencing technologies, we are able to characterize and study gene expression levels and associated regulatory mechanisms in a large number of individuals and species at an unprecedented resolution and scale. We have thus gained new insights into the evolutionary pressures that shape gene expression levels and have developed an appreciation for the relative importance of evolutionary changes in different regulatory genetic and epigenetic mechanisms. The current challenge is to link gene regulatory changes to adaptive evolution of complex phenotypes. Here we mainly focus on comparative studies in primates and how they are complemented by studies in model organisms.

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Figure 1: Regulatory mechanisms that can be investigated using comparative genomic approaches.
Figure 2: Inter-species differences in transcription factor binding.

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Acknowledgements

We thank M. Nobrega and N. Sakab for helping to generate Fig. 1, M. Ward and D. Odom for generating Fig. 2 on the basis of their comparative data and G. Perry for help with the figures in Boxes 2 and 3. We thank J. Pritchard, Z. Gauhar and the three anonymous reviewers for their comments on the manuscript. This work was supported by US National Science Foundation grant IOS-0843504 and US National Institutes of Health (NIH) grant P50 GM081892 to I.R., and NIH grants GM077959 and GM084996 to Y.G. I.G.R. is a Sir Henry Wellcome Postdoctoral Fellow.

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  1. Department of Human Genetics, University of Chicago,

    Irene Gallego Romero & Yoav Gilad

  2. Department of Ecology and Evolution, University of Chicago, Chicago, 60637, Illinois, USA

    Ilya Ruvinsky

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  1. Irene Gallego Romero
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  2. Ilya Ruvinsky
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Correspondence to Yoav Gilad.

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Romero, I., Ruvinsky, I. & Gilad, Y. Comparative studies of gene expression and the evolution of gene regulation. Nat Rev Genet 13, 505–516 (2012). https://doi.org/10.1038/nrg3229

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