Evolution of developmental regulation in the vertebrate FgfD subfamily

Abstract

Fibroblast growth factors (Fgfs) encode small signaling proteins that help regulate embryo patterning. Fgfs fall into seven families, including FgfD. Non-vertebrate chordates have a single FgfD gene; mammals have three (Fgf8, Fgf17, and Fgf18); and teleosts have six (fgf8a, fgf8b, fgf17, fgf18a, fgf18b, and fgf24). What are the evolutionary processes that led to the structural duplication and functional diversification of FgfD genes during vertebrate phylogeny? To study this question, we investigated conserved syntenies, patterns of gene expression, and the distribution of conserved non-coding elements in FgfD genes of stickleback and zebrafish, and compared them to data from cephalochordates, urochordates, and mammals. Genomic analysis suggests that Fgf8, Fgf17, Fgf18 and Fgf24 arose in two rounds of whole genome duplication at the base of the vertebrate radiation; that fgf8 and fgf18 duplications occurred at the base of the teleost radiation, and that Fgf24 is an ohnolog that was lost in the mammalian lineage. Expression analysis suggests that ancestral subfunctions partitioned between gene duplicates and points to the evolution of novel expression domains. Analysis of conserved non-coding elements (CNEs), at least some of which are candidate regulatory elements, suggests that ancestral CNEs partitioned between gene duplicates. These results help explain the evolutionary pathways by which the developmentally important family of FgfD molecules arose and the deduced principles that guided FgfD evolution are likely applicable to the evolution of developmental regulation in many vertebrate multigene families.

Vgll2a is required for neural crest cell survival during zebrafish craniofacial development

“…Thus, we believe Fgf3 could represent an FGF source capable of regulating vgll2a expression. It is likely, however, that Fgf3 could act redundantly with one or more additional Fgf ligands such as Fgf8-related Fgf24, which is also expressed in the pharyngeal pouches (Jovelin et al, 2009; Mercader et al, 2006). …”

Conservation of gene linkage in dispersed vertebrate NK homeobox clusters

“…3 and 4; see also Wotton et al 2008b;Jovelin et al 2009). However, Lbx2 does not currently exist in the X. tropicalis genome or in medaka; Tlx2 has not been identified in the chicken genome or in medaka; and Tlx1 has not been identified in the Tetraodon genome (Figs.…”

“…3 and 4). The intergenic region of the teleosts also contains three genes as opposed to the one gene found in the mammalian region (see also Wotton et al 2008b;Jovelin et al 2009). In addition, with the exception of duplicated Hmx4 and Msx1 genes in fugu, a duplicate Hmx1 gene in Tetraodon and duplicate Hmx1 and Hmx4 genes in medaka and stickleback, no additional copies of these dispersed group III genes are found in teleosts, suggesting that they were probably lost soon after the teleost-specific genome duplication event (Fig.…”

Pleiotropic Constraints, Expression Level, and the Evolution of miRNA Sequences

“…Lineage-specific duplications and losses of developmental regulatory genes contribute to their functional diversification (Canestro et al 2009; Jovelin et al 2010), and can generate genetic incompatibilities leading to speciation (Lynch and Force 2000). The redeployment of this shared toolkit within regulatory networks, through the evolution of transcription factor binding sites, in various tissues during development is thought to have played a major role in the evolution of animal form (Carroll 2008).…”