One of the primary hypotheses of Sean Carroll’s model of evo-devo is that cis-regulatory elements (CREs) are the primary drivers of morphological evolution (see here). This hypothesis is controversial in the evolutionary genetics community. Because it’s hard to examine the effect of CREs on phenotypes at a genome-wide scale, the problem must be reduced into smaller elements. One such element that has been the subject of previous studies is the role of cis and trans mutations in the evolution of gene expression. I have previously discussed some results that shed light on this issue. The basic conclusion from those results is that the data indicate that both cis and trans changes play an important role in the evolution of gene expression.
A previous study examined the proportion of expression differences between two Drosophila species that were due to cis changes, and the fraction due to trans changes. That study found that the cis changes play a larger role, but trans mutations are also important. A new paper reports the results of a similar experiment in yeast. The authors of this study found that trans changes play a larger role than cis changes in expression differences between two strains of yeast. They do, however, acknowledge that cis changes also play an important role.
That brings us to the title of this post: is Sean Carroll wrong? Keeping in mind that these studies examine gene expression rather than morphology, it appears that Carroll is at least partially wrong. While CREs are important in teh evolution of phenotypes, they are not as important as Carroll sells them to be. One caveat is that trans effects on expression differences may, ultimately, be due to changes in CREs of transcription factors. Changing the expression pattern of a transcription factor may, ultimately, affect the transcription of multiple other genes. While this will show up as a trans effect in the assays to distinguish cis and trans changes, it is actually due to a mutation in a CRE of a regulatory gene located upstream in some gene expression pathway.
Hoekstra HE, and Coyne JA. 2007 The locus of evolution: evo devo and the genetics of adaptation. Evolution 61:995-1016 doi:10.1111/j.1558-5646.2007.00105.x
Prud’homme B, Gompel N, and Carroll SB. 2007. Emerging principles of regulatory evolution. Proc Natl Acad Sci USA 104:8605-8612 doi:10.1073/pnas.0700488104
Wang D, Sung H-M, Wang T-Y, Huang C-J, Yang P, et al. 2007. Expression evolution in yeast genes of single-input modules is mainly due to changes in trans-acting factors. Genome Res 17:1161-1169 doi:10.1101/gr.6328907
Wittkopp PT, Haerum BK, and Clark AG. 2004. Evolutionary changes in cis and trans gene regulation. Nature 430:85-88 doi:10.1038/nature02698