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BMC Evol Biol
2018 Dec 04;181:182. doi: 10.1186/s12862-018-1306-y.
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The evolution of ependymin-related proteins.
McDougall C
,
Hammond MJ
,
Dailey SC
,
Somorjai IML
,
Cummins SF
,
Degnan BM
.
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BACKGROUND: Ependymins were originally defined as fish-specific secreted glycoproteins involved in central nervous system plasticity and memory formation. Subsequent research revealed that these proteins represent a fish-specific lineage of a larger ependymin-related protein family (EPDRs). EPDRs have now been identified in a number of bilaterian animals and have been implicated in diverse non-neural functions. The recent discoveries of putative EPDRs in unicellular holozoans and an expanded EPDR family with potential roles in conspecific communication in crown-of-thorns starfish suggest that the distribution and diversity of EPDRs is significantly broader than currently understood.
RESULTS: We undertook a systematic survey to determine the distribution and evolution of EPDRs in eukaryotes. In addition to Bilateria, EPDR genes were identified in Cnidaria, Placozoa, Porifera, Choanoflagellatea, Filasterea, Apusozoa, Amoebozoa, Charophyta and Percolozoa, and tentatively in Cercozoa and the orphan group Malawimonadidae. EPDRs appear to be absent from prokaryotes and many eukaryote groups including ecdysozoans, fungi, stramenopiles, alveolates, haptistans and cryptistans. The EPDR family can be divided into two major clades and has undergone lineage-specific expansions in a number of metazoan lineages, including in poriferans, molluscs and cephalochordates. Variation in a core set of conserved residues in EPDRs reveals the presence of three distinct protein types; however, 3D modelling predicts overall protein structures to be similar.
CONCLUSIONS: Our results reveal an early eukaryotic origin of the EPDR gene family and a dynamic pattern of gene duplication and gene loss in animals. This research provides a phylogenetic framework for the analysis of the functional evolution of this gene family.
Fig. 1. Distribution of EPDR proteins in Eukaryota. The cladogram to the left indicates the currently accepted phylogenetic relationships among taxa [38, 64–70]. The presence of EPDR sequences in particular groups is indicated by blue boxes. The clade membership (according to phylogenetic analysis) and profile membership (based upon conserved cysteine residue patterns) of each group is indicated in the schematic on the right
Fig. 2. Alignment of representative EPDR protein sequences. Comparative alignments of representatives displaying each cysteine residue profile are shown. D. rerio 134034 is a fish ependymin and is included as a representative of profile 1. The signal peptide is indicated by a grey box, and conserved cysteine residues are highlighted in yellow and numbered at the top of the alignment. The sequence logos were calculated from the alignment of all detected EPDR proteins for each profile (see Additional file 4), and thus do not directly correspond to the representative sequences shown. The overall height of each column corresponds to the degree of conservation at that site, and the height of each letter corresponds to the overall frequency of that amino acid. The colouring of species names corresponds to the phylogenetic groups to which the species belong, and follows the scheme established in Fig. 1
Fig. 3. Summarised phylogenetic analysis of EPDR protein sequences. Colouring of the branches corresponds to the phylogenetic groups to which the species belong, and follows the scheme established in Fig. 1. Maximum likelihood tree, branches with high support from both analyses (maximum likelihood bootstrap values > 80 and Bayesian posterior probability values > 90) are indicated by a solid line, those with bootstrap values > 50 or posterior probability values > 70 are indicated by a dashed line, and those with lower support are indicated by a dotted line. The two major EPDR clades are indicated by the outer circle, the cysteine profile displayed by the sequences is indicated by the inner circle. Major clades identified by Suárez-Castillo and García-Arrarás [10] are also indicated (Brain, Tj, and MERPs), including those proposed to belong to the ‘basal’ clade (black dots). The scale bar indicates the number of substitutions per site. For a complete tree including support values and individual sequence names refer to Additional file 6
Fig. 4. Predicted 3D structure of representative EPDRs. a-c; three different views of Capsaspora owczarzaki 30864 (clade 1, profile 1, gold), Saccoglossus kowalevskii 291225509 (clade 2, profile 2, blue) and Naegleria gruberi EFC42264 (clade 2, profile 3, pink) EPDR sequences, superimposed. All three sequences are predicted to form a twisted beta-sheet structure that surrounds a central pocket (visible in C). d. Surface rendering of C, based on the S. kowalevskii sequence. The shading in the centre indicates the location of the pocket. Panels E-J present individual predicted 3D structures of C. owczarzaki 30864 (e), S. kowalevskii 291225509 (f), N. gruberi EFC42264 (g), Danio rerio 134034 (a fish brain ependymin; h), Chaetosphaeridium globosum HO349164 (i), and Aplysia californica (j), respectively, in a similar orientation. Highly conserved cysteine residues are indicated in green. The highly conserved proline (position 150 of alignment) is located at the bottom of the pocket and is indicated in yellow, except for D. rerio 134034 in which it is absent. Predicted glycosylation sites are indicated in red. All sequences display similar predicted structures, however there appears to be some divergence in the portion of the protein distal to the pocket (left of figure), particularly in profile 3 proteins
Fig. 5. Proposed evolution of the EPDR family. The presence of EPDR sequences in particular groups is indicated by blue boxes, and the evolutionary origin of major EPDR clades is depicted by solid bars. The unikont ancestor likely possessed both clade 1 and clade 2 EPDRs, however it is possible that clade 1 EPDRs arose later, in the opisthokont ancestor. Major expansion of EPDR genes occurred in lineages indicated by an asterisk
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