Old Dog, New Tricks: How Evolution Transformed a Transcription Factor

A central challenge of biology is to explain how changes in the genome have supported the evolution of morphology and given rise to the biodiversity we have today. During embryonic development, the genetic sequence of an organism is “read out” to produce its anatomy. As part of this developmental process, networks of transcription factors play a key role in regulating gene expression and establishing cell fates. Hence, studying how transcription factors evolve will help us understand how new animal morphologies have arisen in nature.

It is widely accepted that evolution can act by changing when and where transcription factors are expressed in the embryo, but the role of changes in the structure of transcription factors themselves has been more controversial. This is because the latter could alter the ability of transcription factors to bind to hundreds of downstream targets throughout the genome and is likely to be detrimental to the organism.

Mutations in the structure of transcription factors might be buffered, however, in the event of gene duplication, which frees one copy of the gene from its usual constraints. In theory, the duplicated gene would be free to change its structure and produce a transcription factor with a novel function.

In recent work published by the Ettensohn lab, Jian Ming Khor and Charles Ettensohn show that an ancient gene duplication event had exactly this effect.  Their work focused on the embryonic development of echinoderms- spiny, marine animals that are a valuable experimental model for developmental and evolutionary studies. All echinoderms have a distinctive, biomineralized skeleton.

Previous work from the lab had shown that the transcription factor Alx1 plays a critically important role in skeletal development. In their new study, Khor and Ettensohn discovered that, following an ancient gene duplication event that gave rise to alx1, the structure of the gene changed. The effect of this genetic change was to add a small domain to the Alx1 protein that allowed it to acquire its new and important developmental function. Taken together, this study deepens our understanding of how transcription factors evolve and how such changes have led to new animal morphologies.

^{Khor JM, Ettensohn CA. Functional divergence of paralogous transcription factors supported the evolution of biomineralization in echinoderms. Elife. 2017 Nov 20;6. pii: e32728. doi: 10.7554/eLife.32728. PMID: 29154754}