Abstract
Alx1 is a pivotal transcription factor in a gene regulatory network that controls skeletogenesis throughout the echinoderm phylum. We performed a structure-function analysis of sea urchin Alx1 using a rescue assay and identified a novel, conserved motif (Domain 2) essential for skeletogenic function. The paralogue of Alx1, Alx4, was not functionally interchangeable with Alx1, but insertion of Domain 2 conferred robust skeletogenic function on Alx4. We used cross-species expression experiments to show that Alx1 proteins from distantly related echinoderms are not interchangeable, although the sequence and function of Domain 2 are highly conserved. We also found that Domain 2 is subject to alternative splicing and provide evidence that this domain was originally gained through exonization. Our findings show that a gene duplication event permitted the functional specialization of a transcription factor through changes in exon-intron organization and thereby supported the evolution of a major morphological novelty.
Highlights
The evolution of animal form has occurred through evolutionary modifications to the developmental programs that give rise to anatomy
Because previous work has shown that the effects of Alx1 are dose-dependent (Ettensohn et al, 2007), we tested a range of concentrations of LvAlx1.WT.GFP mRNA (1–4 mg/mL) and found that higher concentrations (3–4 mg/mL) inhibited primary mesenchyme cells (PMCs) specification, consistent with previous findings
Our studies show that a short form of Alx1 containing only the homeodomain and Domains 1 and 2 is able to substantially rescue PMC specification and skeletal morphogenesis in sea urchin (L. variegatus) embryos
Summary
The evolution of animal form has occurred through evolutionary modifications to the developmental programs that give rise to anatomy. There is considerable evidence that evolutionary changes in transcriptional networks have played an important role in morphological evolution (McGregor et al, 2007). It is widely accepted that mutations in non-coding, cis-regulatory elements (CREs) have played a major role in the evolution of transcriptional networks (Rubinstein and de Souza, 2013; Wittkopp and Kalay, 2011). The role of protein-level changes in transcription factors, has been more controversial (Cheatle Jarvela and Hinman, 2015; Lynch and Wagner, 2008). Mutations in coding regions might be buffered, in the event of gene duplication, which frees one copy of the gene from selective pressure, thereby allowing it to evolve novel functions (Conant and Wolfe, 2008). Whether functional specialization of paralogous transcription factors has played a significant role in the evolution of novel structures remains an open question
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