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BMC Genomics
2010 Jan 15;11:37. doi: 10.1186/1471-2164-11-37.
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A manual collection of Syt, Esyt, Rph3a, Rph3al, Doc2, and Dblc2 genes from 46 metazoan genomes--an open access resource for neuroscience and evolutionary biology.
Craxton M
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BACKGROUND: Synaptotagmin proteins were first identified in nervous tissue, residing in synaptic vesicles. Synaptotagmins were subsequently found to form a large family, some members of which play important roles in calcium triggered exocytic events. These members have been investigated intensively, but other family members are not well understood, making it difficult to grasp the meaning of family membership in functional terms. Further difficulty arises as families are defined quite legitimately in different ways: by common descent or by common possession of distinguishing features. One definition does not necessarily imply the other. The evolutionary range of genome sequences now available, can shed more light on synaptotagmin gene phylogeny and clarify family relationships. The aim of compiling this open access collection of synaptotagmin and synaptotagmin-like sequences, is that its use may lead to greater understanding of the biological function of these proteins in an evolutionary context.
RESULTS: 46 metazoan genomes were examined and their complement of Syt, Esyt, Rph3a, Rph3al, Doc2 and Dblc2 genes identified. All of the sequences were compared, named, then examined in detail. Esyt genes were formerly named Fam62. The species in this collection are Trichoplax, Nematostella, Capitella, Helobdella, Lottia, Ciona, Strongylocentrotus, Branchiostoma, Ixodes, Daphnia, Acyrthosiphon, Tribolium, Nasonia, Apis, Anopheles, Drosophila, Caenorhabditis, Takifugu, Tetraodon, Gasterosteus, Oryzias, Danio, Xenopus, Anolis, Gallus, Taeniopygia,Ornithorhynchus, Monodelphis, Mus and Homo. All of the data described in this paper is available as additional files.
CONCLUSIONS: Only a subset of synaptotagmin proteins appear able to function as calcium triggers. Syt1, Syt7 and Syt9 are ancient conserved synaptotagmins of this type. Some animals carry extensive repertoires of synaptotagmin genes. Other animals of no less complexity, carry only a small repertoire. Current understanding does not explain why this is so. The biological roles of many synaptotagmins remain to be understood. This collection of genes offers prospects for fruitful speculation about the functional roles of the synaptotagmin repertoires of different animals and includes a great range of biological complexity. With reference to this gene collection, functional relationships among Syt, Esyt, Rph3a, Rph3al, Doc2 and Dblc2 genes, which encode similar proteins, can better be assessed in future.
Figure 1. Summary of the genes collected from marine invertebrate genomes. The website of the organisation which sequenced the genome is listed below the organism name. Underneath the Gene Name heading, gene symbols are listed. Red symbols indicate sequences containing all ten acidic amino acid positions required for function as a calcium trigger for exocytosis.
Figure 2. Summary of the genes collected from ecdysozoan genomes. The websites of the organisations which sequenced the genome or which provide access to multiple genomes within a single genus, are listed below the organism name. Underneath the Gene Name heading, gene symbols are listed. Red symbols indicate sequences containing all ten acidic amino acid positions required for function as a calcium trigger for exocytosis. Websites for the relevant nomenclature authorities are listed alongside the Gene Name heading. Gene symbols within brackets are currently officially approved, but in conflict with the nomenclature proposed here.
Figure 3. Summary of the genes collected from Vertebrate genomes. The websites of the organisations which sequenced the genome or which provide this information, are listed below the organism name. Underneath the Gene Name heading, gene symbols are listed. Red symbols indicate sequences containing all ten acidic amino acid positions required for function as a calcium trigger for exocytosis. Websites for the relevant nomenclature authorities are listed alongside the Gene Name heading. Gene symbols within brackets are currently officially approved, but in conflict with the nomenclature proposed here.
Figure 4. Syt orthologues and paralogues in M. musculus. Percent identity scores produced by the align facility at EBI, of pairwise comparisons of full length protein sequences, are listed. Top scores from mouse versus lizard comparisons are highlighted in blue, indicating an orthologous relationship between the mouse gene and the evolutionarily more ancient lizard gene. Top scores from comparisons between mouse and the much more evolutionarily ancient polychaete worm, Capitella, are highlighted in green, indicating that of these mouse genes, Syt1, Syt4, Syt9 and Syt16 are orthologous to genes in Capitella.
Figure 5. Pairwise comparisons of Syt1 paralogues in vertebrates. Percent identity scores produced by the align facility at EBI, of pairwise comparisons of full length protein sequences, are listed. Top scores are highlighted in blue, indicating an orthologous relationship between the compared genes.
Figure 6. Synteny of Syt1 paralogues in D. rerio, X. tropicalis and H. sapiens. Gene symbols for four groups of neighbouring genes in H. sapiens, are enclosed by a black box. Within the red box, the chromosomal locations of each gene in the current human genome reference sequence, are indicated along with a reference transcript sequence. The genomic locations and transcript sequences for the X. tropicalis gene relatives are within the green box and those for D. rerio are within the blue box.
Figure 7. Genomic sequence surrounding coding exons 4 and 5 in mouse Doc2g and the equivalent human region. Genomic sequence surrounding coding exons 4 and 5 of mouse Doc2g and the equivalent region in human, are shown. Exonic and intronic sequences are indicated. The reading frame is indicated by grey bars between codons. The single nucleotide deletion in the human exon 5 region is highlighted with a red exclamation mark. The deletion in human exon 5 disrupts the reading frame, leading to a premature termination codon which is boxed and highlighted with a red exclamation mark. An alternative splice acceptor dinucleotide which could restore the correct reading frame to human exon 5 is indicated by a blue arrow. Blue bars between the first few codons indicate the reading frame were the alternative splice acceptor to be functional. Human exon 5 has an alternative start codon, which is boxed and highlighted with a question mark. There is a possibility that this start codon could allow normally spliced transcripts to be translated into the N-terminal and C-terminal protein products listed in additional file 50.
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