Evolution of a genomic regulatory domain: The role of gene co-option and gene duplication in the Enhancer of split complex

Abstract

The Drosophila Enhancer of split complex [E(spl)-C] is a remarkable complex of genes many of which are effectors or modulators of Notch signaling. The complex contains different classes of genes including four bearded genes and seven basic helix-loop-helix (bHLH) genes. We examined the evolution of this unusual complex by identifying bearded and bHLH genes in the genome sequences of Arthropods. We find that a four-gene E(spl)-C, containing three bHLH genes and one bearded gene, is an ancient component of the genomes of Crustacea and Insects. The complex is well conserved in insects but is highly modified in Drosophila, where two of the ancestral genes of the complex are missing, and the remaining two have been duplicated multiple times. Through examining the expression of E(spl)-C genes in honeybees, aphids, and Drosophila, we determined that the complex ancestrally had a role in Notch signaling. The expression patterns of genes found inserted into the complex in some insects, or that of ancestral E(spl)-C genes that have moved out of the complex, imply that the E(spl)-C is a genomic domain regulated as a whole by Notch signaling. We hypothesize that the E(spl)-C is a Notch-regulated genomic domain conserved in Arthropod genomes for around 420 million years. We discuss the consequence of this conserved domain for the recruitment of novel genes into the Notch signaling cascade.

Comparative and Evolutionary Analysis of the HES/HEY Gene Family Reveal Exon/Intron Loss and Teleost Specific Duplication Events

“…Fruit fly contained 13 HES/HEY (1 HEY1/2/L, 11 HES, and one resembled DEC1/2). These fruit fly HES/HEY genes in our results were also studied and clustered with genes of other Arthropods in a previous study, which focused on the evolution of the Enhancer of split complex including several HES/HEY genes and other genes [58]. Lumbricus rubellus (Lophotrochozoa) had 5 HES/HEY (2 HEY1/2/L, 3 short sequences which may be incomplete sequences).…”

Ancestral and conserved cis-regulatory architectures in developmental control genes

“…Both the bHLH repressor and Brd family genes shown in Fig. 3 typically occupy the same positions in the respective Enhancer of split gene complexes [E(spl)-Cs] of these species; moreover, Bayesian phylogenetic analysis fully supports the orthology of the Hes genes (Duncan and Dearden, 2010). We emphasize that, because of their low complexity, we cannot argue strongly for or against the conservation of the P and E sites that we have indicated as part of the shared architectures (see, however, Fig.…”

“…A: Diagrams of orthologous Hes -class bHLH repressor genes located in the E(spl)-C of various insect species; these belong to the “E(spl)-C bHLH-1” clade described by Duncan and Dearden (Duncan and Dearden, 2010), and are labeled here as “bHLHR-1” for clarity. B: Diagrams of orthologous Brd family genes located in the E(spl)-C of various arthropod species.…”

Essential Roles of Da Transactivation Domains in Neurogenesis and in E(spl)-Mediated Repression

“…E(spl) proteins constitute a seven-member protein family of bHLH-O repressors that have arisen from recent gene duplication events in drosophilids (20,62) and show partially redundant activities, with the most notable being the suppression of neural commitment, where they antagonize proneural proteins (44,51,66). We showed here that Da AD1 is an interaction surface for E(spl) proteins.…”