Click
here to close Hello! We notice that
you are using Internet Explorer, which is not supported by Echinobase
and may cause the site to display incorrectly. We suggest using a
current version of Chrome,
FireFox,
or Safari.
Front Neurosci
2019 Mar 15;13:109. doi: 10.3389/fnins.2019.00109.
Show Gene links
Show Anatomy links
The Natural History of Teneurins: A Billion Years of Evolution in Three Key Steps.
Wides R
.
???displayArticle.abstract???
The entire evolutionary history of the animal gene family, Teneurin, can be summed up in three key steps, plus three salient footnotes. In a shared ancestor of all bilaterians, the first step began with gene fusions that created a protein with an amino-terminal intracellular domain bridged via a single transmembrane helix to extracellular EGF-like domains. This first step was completed with a further gene fusion: an additional carboxy-terminal stretch of about 2000 amino acids (aa) was adopted, as-a-whole, from bacteria. The 2000 aa structure in Teneurin was recently solved in three dimensions. The 2000 aa region appears in a number of bacteria, yet was co-opted solely into Teneurin, and into no other eukaryotic proteins. Outside of bilaterian animals, no Teneurins exist, with a "Monosiga brevicollis caveat" brought below, as 'the third footnote." Subsequent to the "urTeneurin's" genesis-by-fusions, all bilaterians bore a single Teneurin gene, always encoding an extraordinarily conserved Type II transmembrane protein with invariant domain content and order. The second key step was a duplication that led to an exception to singleton Teneurin genomes. A pair of Teneurin paralogs, Ten-a and Ten-m, are found in representatives of all four Arthropod sub-phyla, in: insects, crustaceans, myriapods, and chelicerates. In contrast, in every other protostome species' genome, including those of all non-Arthropod ecdysozoan phyla, only a single Teneurin gene occurs. The closest, sister, phylum of arthropods, the Onychophorans (velvet worms), bear a singleton Teneurin. Ten-a and Ten-m therefore arose from a duplication in an urArthropod only after Arthropods split from Onychophorans, but before the splits that led to the four Arthropod sub-phyla. The third key step was a quadruplication of Teneurins at the root of vertebrate radiation. Four Teneurin paralogs (Teneurins 1 through 4) arose first by a duplication of a single chordate gene likely leading to one 1/4-type gene, and one 2/3-type gene: the two copies found in extant jawless vertebrates. Relatively soon thereafter, a second duplication round yielded the -1, -2, -3, and -4 paralog types now found in all jawed vertebrates, from sharks to humans. It is possible to assert that these duplication events correlate well to the Ohno hypothesized 2R (two round) vertebrate whole genome duplication (WGD), as refined in more recent treatments. The quadruplication can therefore be placed at approximately 400 Myr ago. Echinoderms, hemichordates, cephalochordates, and urochordates have only a single copy of Teneurin in their genomes. These deuterostomes and non-vertebrate chordates provide the anchor showing that the quadruplication happened at the root of vertebrates. A first footnote must be brought concerning some of the 'invertebrate' relatives of vertebrates, among Deuterostomes. A family of genes that encode 7000 aa proteins was derived from, but is distinct from, the Teneurin family. This distinct family arose early in deuterostomes, yet persists today only in hemichordate and cephalochordate genomes. They are named here TRIPs (Teneurin-related immense proteins). As a second of three 'footnotes': a limited number of species exist with additional Teneurin gene copies. However, these further duplications of Teneurins occur for paralog types (a, m, or 1-4) only in specific lineages within Arthropods or Vertebrates. All examples are paralog duplications that evidently arose in association with lineage specific WGDs. The increased Teneurin paralog numbers correlate with WGDs known and published in bony fish, Xenopus, plus select Chelicerates lineages and Crustaceans. The third footnote, alluded to above, is that a Teneurin occurs in one unicellular species: Monosiga brevicollis. Teneurins are solely a metazoan, bilaterian-specific family, to the exclusion of the Kingdoms of prokaryotes, plants, fungi, and protists. The single exception occurs among the unicellular, opisthokont, closest relatives of metazoans, the choanoflagellates. There is a Teneurin in Monosiga brevicollis, one species of the two fully sequenced choanoflagellate species. In contrast, outside of triploblast-bilaterians, there are no Teneurins in any diploblast genomes, including even sponges - those metazoans closest to choanoflagellates. Perhaps the 'birth' of the original Teneurin occurred in a shared ancestor of M. brevicollis and metazoans, then was lost in M. brevicollis' sister species, and was serially and repeatedly lost in all diploblast metazoans. Alternatively, and as favored above, it first arose in the 'urBilaterian,' then was subsequently acquired from some bilaterian via horizontal transfer by a single choanoflagellate clade. The functional partnership of Teneurins and Latrophilins was discovered in rodents through the LPH1-TENM2 interaction. Recent work extends this to further members of each family. Surveying when the interacting domains of Teneurins and Latrophilins co-exist within different organisms can give an indication of how widespread their functional cooperation might be, across bilaterians. Paralog number for the two families is relatively correlated among bilaterians, and paralog numbers underwent co-increase in the WGDs mentioned above. With co-increasing paralog numbers, the possible combinatorial pairs grow factorially. This should have a significant impact for increasing nervous system complexity. The 3 key events in the 'natural history' of the Teneurins and their Latrophilin partners coincide with the ascendance of particularly successful metazoan clades: bilaterians; arthropods; and vertebrates. Perhaps we can attribute some of this success to the unique Teneurin family, and to its partnership with Latrophilins.
Figure 1. A model for “assembly-by-fusions” of the first Teneurin, or urTeneurin. (A) The emergence of Teneurin structure is modeled as a series of fusions of at least four genes. Protein domains encoded by these genes are diagrammed as four well recognized, discrete, Teneurin regions. “IC” is the intracellular domain, “TMb” is the transmembrane spanning region, and “EGFs” represents the seven or eight EGF-like repeats plus small associated domains. The “2000 amino acid ‘super-fold’ from bacteria” is a region recently recognized to share homology with dozens of proteins found in select prokaryotes. The ‘additions’ shown in the (A) diagram are not meant to imply a chronological order from left to right. (B) The four region names from panel A are reused above a linear representation of Teneurin. The extracellular region of Teneurin 2, as solved by Jackson et al. (2018) (chicken), and Li et al. (2018) (human), along with Teneurin 3 of mouse (Jackson et al., 2018), also had domain names assigned within the super-fold, as shown beneath the linear representation. TTR, transthyretin; FN, fibronectin; NHL, NCL/HT2A/Lin41 domain; YD, a repeat motif; ABD, antibiotic binding domain; and beta-propeller and barrel protein folds. (C) Five best homologies of Teneurin to prokaryotic proteins. Each have nearly 2000 aa acids of homology at more than a 27% amino acid identity level. The alignments start just after the Teneurin EGF-like repeats, and continue almost to the Teneurin carboxy terminus. In (A), note that the shape of the cartoon “2000 aa ‘super-fold”’ is based on the extraordinarily highly concurring pictures of the structure from the Jackson paper and the Li paper, and therefore on the shape that evolution has delivered.
Figure 2. Teneurins from selected representatives of metazoans. An unrooted phylogram of Teneurin protein sequences shows the relatedness of examples from several phyla. Starting with Deuterostomes, on the left side of the figure, the Teneurins that appear are as follows: that of the Echinoderm Strongylocentrotus purpuratus (Sea Urchin); those of the Tunicates Ciona intestinalis and Ciona savignyi; and the four Teneurin paralogs of Homo sapiens (Human 1–Human 4). Continuing clockwise, Teneurins appear for the Nematode Caenorhabditis elegans (C. elegans Ten-1), for the flatworm Platyhelminthes Schistosoma mansoni and Schmidtea mediterranea, for the Molluscs Lottia gigantea and Aplysia californica, and for the roundworm Annelid Capitella telata (Capitella). The two paralogs Ten-a and Ten-m each appear in every Arthropod: for the tick Ixodes scapularis (Tick), the millipede Strigamia maritima (Strigamia), the fruit fly Drosophila melanogaster (Fly), and the water flea Crustacean Daphnia pulex (Daphnia).
Figure 3. Arthropods have two Teneurin paralogs, Ten-a and Ten-m, while all other protostome genomes have one ‘singleton’ Teneurin. (A) A representation of Ecdysozoan phyla, as ordered in a graphical abstract of Borner et al. (2014) in Molecular Phylogenetics and Evolution. Deuterostomes, and some non-Ecdysozoan phyla, including Annelids, Platyhelminthes, and Molluscs, also appear. The insects and crustacean sub-phyla are represented together as “Pancrustacea.” On the right side of the panel, the numbers of Teneurin paralog types found for protostome species are listed. Except for Arthropods, all protostome genomes bear one ‘singleton’ Teneurin. (B) Protostome Teneurin protein sequences were compared using Clustal Omega. Teneurins from the following species were used: Schistosoma mansoni from Platyhelminthes, Caenorhabditis elegans from Nematodes, Hypsibius dujardini (a Tardigrade), Euperipatoides rowelli (an Onychophoran), Priapulus caudatus, Lottia gigantea from molluscs; and Capitella telata from Annelids. For Arthropods, Ten-a and Ten-m were used from Ixodes scapularis (Ixodes Tick), the millipede Strigamia maritima (Strig-mar), the fruit fly Drosophila melanogaster (Fly), and the water flea Daphnia pulex (Daphnia-pul). Arthropod Ten-a and Ten-m appear on a colored background. Note that even the ‘sister phylum’ of Arthropoda, Onychophora, has a singleton Teneurin.
Figure 4. Deuterostome history of Teneurins, displaying the rise of the TRIP family in protochordates, and the quadruplication of Teneurins in vertebrates. (A) A diagram summarizing the Deuterostome history of Teneurins and TRIPs (Teneurin related immense proteins) use the Teneurin shaped icon “assembled” in Figure 1A. A black icon represents the Deuterostome ancestral Teneurin singleton and all singleton Teneurins on the tree. The larger TRIP icon is green, and represents the larger, 7000 aa TRIP protein. Teneurin paralogs in jawless and jawed vertebrates are products of duplications, and appear in color. Phylum names appear with bold letters, and sub-phylum and class names are not bold. Larger groupings (proto-chordates and Ambulacraria) also appear. (B) A Clustal Omega alignment of four TRIP proteins in their entirety. They each have a greater than 6500 aa length, and align from end to end with high homology. One TRIP is from the hemichordate acorn worm Saccoglossus kowalevskii (S. kow), one is from the cephalochordate lancelet Branchiostoma floridae, and two are from the lancelet Branchiostoma belcheri. The S. kowalevskii protein annotation had to be constructed ‘manually’ to overcome a large assembly inversion error in its host genomic scaffold. One of the two B. belcheri protein annotations had to be constructed ‘manually’ from adjacent contigs in the genome assembly. The three hemichordate TRIP proteins from the hemichordate acorn worm Ptychodera flava are not included in this alignment, but are fully homologous, and are much closer to the S. kowalevskii sequence. The cephalochordate Asymmetron lucayanum TRIP is not shown, but is more homologous to the other lancelets’ TRIPs. (C) Deuterostome Teneurins are aligned together with TRIP proteins. Only the N-terminal 2700 aa of the TRIPs are used for the alignment. TRIPs’ sequences that overlap Teneurins strongly partition away from Teneurins. The species used include those in (B), plus the sea star Acanthaster planci, the sea urchin Stronglyocentrotus purpulatus, the tunicate Ciona intestinalis, and the four mouse Teneurins. (D) A Clustal Omega alignment of Teneurins from agnathans (jawless vertebrates), sharks, and fish. The species used were Rhincodon typus (elephant shark), Rhincodon typus (whale shark), Danio rerio (zebrafish), Eptatretus burgeri (agnathan, hagfish), and Petromyzon marinus (agnathan, lamprey). Two Teneurin homologs exist in the two agnathans, and were called “TenmA and TenmB.” The TenmB protein of lamprey was too incomplete to use effectively, so it was not included in the alignment. The two Teneurins aligned from hagfish, and the one aligned from lamprey are incomplete protein annotations.
Figure 5. Additional Teneurin paralog copies have arisen in association with Whole Genome Duplications (WGDs) in specific vertebrates and arthropods. (A) A list of Teneurin genes in the diploid frog Xenopus tropicalis and in the allotetraploid Xenopus laevis. They are all shown with their chromosomal locations. X. laevis has duplicates of every Teneurin, and each one is located in syntenically conserved positions, relative to X. tropicalis. (B) A Clustal Omega alignment showing the duplication of Teneurins in the Chelicerate horseshoe crab Limulus polyphemus, that has two Ten-a and two Ten-m genes. It is compared to Onychophoran Teneurin, and to Teneurins of fly, tick, and water flea. As in Figure 3, the species used are Ixodes scapularis (Ixodes Tick), the fruit fly Drosophila melanogaster (Fly), and the water flea Daphnia pulex (Daphnia-pul).
Adams,
The evolution of tenascins and fibronectin.
2015, Pubmed
Adams,
The evolution of tenascins and fibronectin.
2015,
Pubmed
Baumgartner,
Tena, a Drosophila gene related to tenascin, shows selective transcript localization.
1993,
Pubmed
Berthelot,
The rainbow trout genome provides novel insights into evolution after whole-genome duplication in vertebrates.
2014,
Pubmed
Blair,
Molecular phylogeny and divergence times of deuterostome animals.
2005,
Pubmed
Borner,
A transcriptome approach to ecdysozoan phylogeny.
2014,
Pubmed
Boucard,
Latrophilins function as heterophilic cell-adhesion molecules by binding to teneurins: regulation by alternative splicing.
2014,
Pubmed
Caputo Barucchi,
Genome duplication in early vertebrates: insights from agnathan cytogenetics.
2013,
Pubmed
Chipman,
The first myriapod genome sequence reveals conservative arthropod gene content and genome organisation in the centipede Strigamia maritima.
2014,
Pubmed
Dehal,
Two rounds of whole genome duplication in the ancestral vertebrate.
2005,
Pubmed
Ferralli,
The teneurin C-terminal domain possesses nuclease activity and is apoptogenic.
2018,
Pubmed
Hamann,
International Union of Basic and Clinical Pharmacology. XCIV. Adhesion G protein-coupled receptors.
2015,
Pubmed
Hoffmeyer,
Choanoflagellate models - Monosiga brevicollis and Salpingoeca rosetta.
2016,
Pubmed
Howe,
The zebrafish reference genome sequence and its relationship to the human genome.
2013,
Pubmed
Jackson,
Structures of Teneurin adhesion receptors reveal an ancient fold for cell-cell interaction.
2018,
Pubmed
Kenny,
Ancestral whole-genome duplication in the marine chelicerate horseshoe crabs.
2016,
Pubmed
Krishnan,
The origin of GPCRs: identification of mammalian like Rhodopsin, Adhesion, Glutamate and Frizzled GPCRs in fungi.
2012,
Pubmed
Krishnan,
Remarkable similarities between the hemichordate (Saccoglossus kowalevskii) and vertebrate GPCR repertoire.
2013,
Pubmed
Krishnan,
The GPCR repertoire in the demosponge Amphimedon queenslandica: insights into the GPCR system at the early divergence of animals.
2014,
Pubmed
Krishnan,
Evolutionary hierarchy of vertebrate-like heterotrimeric G protein families.
2015,
Pubmed
Leamey,
The teneurins: new players in the generation of visual topography.
2014,
Pubmed
Lelianova,
Alpha-latrotoxin receptor, latrophilin, is a novel member of the secretin family of G protein-coupled receptors.
1997,
Pubmed
Li,
Structural Basis for Teneurin Function in Circuit-Wiring: A Toxin Motif at the Synapse.
2018,
Pubmed
McLysaght,
Extensive genomic duplication during early chordate evolution.
2002,
Pubmed
Minet,
Phylogenetic analysis of teneurin genes and comparison to the rearrangement hot spot elements of E. coli.
2000,
Pubmed
Misof,
Phylogenomics resolves the timing and pattern of insect evolution.
2014,
Pubmed
Mosca,
On the Teneurin track: a new synaptic organization molecule emerges.
2015,
Pubmed
Nei,
Estimation of divergence times from multiprotein sequences for a few mammalian species and several distantly related organisms.
2001,
Pubmed
Nordström,
Independent HHsearch, Needleman--Wunsch-based, and motif analyses reveal the overall hierarchy for most of the G protein-coupled receptor families.
2011,
Pubmed
,
Echinobase
Nossa,
Joint assembly and genetic mapping of the Atlantic horseshoe crab genome reveals ancient whole genome duplication.
2014,
Pubmed
Pasquier,
Gene evolution and gene expression after whole genome duplication in fish: the PhyloFish database.
2016,
Pubmed
Riadi,
Towards the bridging of molecular genetics data across Xenopus species.
2016,
Pubmed
Richter,
Gene family innovation, conservation and loss on the animal stem lineage.
2018,
Pubmed
Schiöth,
The adhesion GPCRs; gene repertoire, phylogeny and evolution.
2010,
Pubmed
Scholz,
The adhesion GPCR latrophilin/CIRL shapes mechanosensation.
2015,
Pubmed
Scholz,
Mechano-dependent signaling by Latrophilin/CIRL quenches cAMP in proprioceptive neurons.
2017,
Pubmed
Schwager,
The house spider genome reveals an ancient whole-genome duplication during arachnid evolution.
2017,
Pubmed
Silva,
Latrophilin 1 and its endogenous ligand Lasso/teneurin-2 form a high-affinity transsynaptic receptor pair with signaling capabilities.
2011,
Pubmed
Snell,
Rotifers as experimental tools for investigating aging.
2015,
Pubmed
Tucker,
Phylogenetic analysis of the teneurins: conserved features and premetazoan ancestry.
2012,
Pubmed
Tucker,
Evidence for the evolution of tenascin and fibronectin early in the chordate lineage.
2009,
Pubmed
Voskoboynik,
The genome sequence of the colonial chordate, Botryllus schlosseri.
2013,
Pubmed
Woelfle,
Teneurins, TCAP, and latrophilins: roles in the etiology of mood disorders.
2016,
Pubmed
Wouters,
Evolution of distinct EGF domains with specific functions.
2005,
Pubmed
Yue,
Conserved Noncoding Elements in the Most Distant Genera of Cephalochordates: The Goldilocks Principle.
2016,
Pubmed
Ziegler,
Teneurin protein family: an emerging role in human tumorigenesis and drug resistance.
2012,
Pubmed
i5K Consortium,
The i5K Initiative: advancing arthropod genomics for knowledge, human health, agriculture, and the environment.
2013,
Pubmed