An unusual choanoflagellate protein released by Hedgehog autocatalytic processing

Abstract

Hedgehog proteins are important cell-cell signalling proteins utilized during the development of multicellular animals. Members of the hedgehog gene family have not been detected outside the Metazoa, raising unanswered questions about their evolutionary origin. Here we report a highly unusual hedgehog-related gene from a choanoflagellate, a close unicellular relative of the animals. The deduced C-terminal domain, Hoglet-C, is homologous to the autocatalytic domain of Hedgehog proteins and is predicted to function in autocatalytic cleavage of the precursor peptide. In contrast, the N-terminal Hoglet-N peptide has no similarity to the signalling peptide of Hedgehog (Hh-N). Instead, Hoglet-N is deduced to be a secreted protein with an enormous threonine-rich domain of unprecedented size and purity (over 200 threonine residues) and two polysaccharide-binding domains. Structural modelling reveals that these domains have a novel combination of features found in cellulose-binding domains (CBD) of types IIa and IIb, and are expected to bind cellulose. We propose that the two CBD domains enable Hoglet-N to bind to plant matter, tethering an amorphous nucleophilic anchor, facilitating transient adhesion of the choanoflagellate cell. Since Hh-C and Hoglet-C are homologous, but Hh-N and Hoglet-N are not, we argue that metazoan hedgehog genes evolved by fusion of two distinct genes.

The genome of the choanoflagellate Monosiga brevicollis and the origin of metazoans

“…The identification of a hedgehog-like gene in a choanoflagellate is not without precedent. A distinct Hint-domain-containing protein, named Hoglet, was identified in the distantly related Monosiga ovata 12 , supporting the idea that isolated signalling components were present in the last common ancestor of choanoflagellates and metazoans.…”

“…Over the past decade or so, evidence supporting this relationship has accumulated from phylogenetic analyses of nuclear and mitochondrial genes [3][4][5][6] , comparative genomics between the mitochondrial genomes of choanoflagellates, sponges and other metazoans 7,8 , and the finding that choanoflagellates express homologues of metazoan signalling and adhesion genes [9][10][11][12] . Furthermore, species-rich phylogenetic analyses demonstrate that choanoflagellates are not derived from metazoans, but instead represent a distinct lineage that evolved before the origin and diversification of metazoans (Fig.…”

A family of diatom-like silicon transporters in the siliceous loricate choanoflagellates

“…These SIT domains are not present in any of the sequenced non-siliceous choanoflagellate species [15,17,38,39], implying a correlation between their presence and lorica biomineralization.…”

Degenerate evolution of the hedgehog gene in a hemichordate lineage

“…18 and 19). The GCF motif is ancient and is deduced to have been present in the gene ancestral to hh because the Hoglet gene of a choanof lagellate also contains GCF (20). The reported sequence of the hh gene in Saccoglossus, however, has a replacement of serine (S) for glycine (G), therefore having SCF instead of GCF ( Fig.…”