Gene Regulation and Speciation

Abstract

Understanding the genetic architecture of speciation is a major goal in evolutionary biology. Hybrid dysfunction is thought to arise most commonly through negative interactions between alleles at two or more loci. Divergence between interacting regulatory elements that affect gene expression (i.e., regulatory divergence) may be a common route for these negative interactions to arise. We review here how regulatory divergence between species can result in hybrid dysfunction, including recent theoretical support for this model. We then discuss the empirical evidence for regulatory divergence between species and evaluate evidence for misregulation as a source of hybrid dysfunction. Finally, we review unresolved questions in gene regulation as it pertains to speciation and point to areas that could benefit from future research.

Keywords: gene expression; gene regulation; hybrid inviability; hybrid sterility; speciation.

Figure 1

The Bateson–Dobzhansky–Muller Model of Hybrid Incompatibility. In the ancestral population, the genotype is AABB. After the two populations are isolated, new mutations arise independently on each lineage as indicated by the asterisks. In one population, A evolves into a, in the other population B evolves into b. In hybrids, negative interactions between the a and b alleles can result in sterility or inviability. The a and b alleles are found together for the first time in hybrids, explaining how this incompatibility could evolve without either lineage experiencing an intermediate state of reduced fitness.

Figure 2

Regulatory Divergence as a Source of Hybrid Incompatibilities. Panels (A) and (B) are schematics of a two-locus model for hybrid incompatibilities. Each hybrid incompatibility arises as a consequence of the molecular interactions between a cis-regulatory region and a trans-acting factor. Changes in binding between interacting regulatory elements affect the expression of a downstream gene. Asterisks represent mutations that become fixed along a lineage. (A) A change to a cis-regulatory region in one species and the interacting trans-acting factor in the other result in hybrid dysfunction. Divergence in this example may be the result of drift or selection. In hybrids, the binding configuration represented by (iii) results in misregulation, while (i), (ii), and (iv) produce normal transcriptional output. This model is a realization of the Bateson–Dobzhansky–Muller model. (B) Lineage specific co-evolution between cis- and trans-regulatory elements result in hybrid dysfunction. In this example, a change in cis is followed by a compensatory change in trans to mask the deleterious effect of the first mutation. In hybrids, the binding configuration represented by (iii) results in misregulation. The binding configuration represented by (ii) results in reduced expression compared to the parents, while the binding configurations represented by (i) and (iv) result in the same expression as in the parents.

Figure 3

Using Allele-Specific Expression To Infer Regulatory Divergence between Species. Differences in the expression of alleles in an F1 can be used to determine whether expression divergence between the parents is due to changes in cis or to changes in trans. (A) Species 1 carries the A allele while species 2 carries the a allele. In the parental species, the transcript abundance of A is 2 and the transcript abundance of a is 3. Differences in the expression of the A and a alleles in the F1 hybrid suggests cis-regulatory divergence between species 1 and 2 because these two alleles are in the same trans-acting environment in the F1. (B) A and a have equal transcript abundances in the F1 hybrid despite the difference in expression seen between the parents. This suggests that differences between the parents are due to changes in trans.