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PubMed2006

Hierarchical clustering algorithm for comprehensive orthologous-domain classification in multiple genomes.

Ortholog identification is a crucial first step in comparative genomics. Here, we present a rapid method of ortholog grouping which is effective enough to allow the comparison of many genomes simultaneously. The method takes as input all-against-all similarity data and classifies genes based on the traditional hierarchical clustering algorithm UPGMA. In the course of clustering, the method detects domain fusion or fission events, and splits clusters into domains if required. The subsequent procedure splits the resulting trees such that intra-species paralogous genes are divided into different groups so as to create plausible orthologous groups. As a result, the procedure can split genes into the domains minimally required for ortholog grouping. The procedure, named DomClust, was tested using the COG database as a reference. When comparing several clustering algorithms combined with the conventional bidirectional best-hit (BBH) criterion, we found that our method generally showed better agreement with the COG classification. By comparing the clustering results generated from datasets of different releases, we also found that our method showed relatively good stability in comparison to the BBH-based methods.

Algorithms↗
PubMed2005

The sequence of rice chromosomes 11 and 12, rich in disease resistance genes and recent gene duplications.

BACKGROUND: Rice is an important staple food and, with the smallest cereal genome, serves as a reference species for studies on the evolution of cereals and other grasses. Therefore, decoding its entire genome will be a prerequisite for applied and basic research on this species and all other cereals. RESULTS: We have determined and analyzed the complete sequences of two of its chromosomes, 11 and 12, which total 55.9 Mb (14.3% of the entire genome length), based on a set of overlapping clones. A total of 5,993 non-transposable element related genes are present on these chromosomes. Among them are 289 disease resistance-like and 28 defense-response genes, a higher proportion of these categories than on any other rice chromosome. A three-Mb segment on both chromosomes resulted from a duplication 7.7 million years ago (mya), the most recent large-scale duplication in the rice genome. Paralogous gene copies within this segmental duplication can be aligned with genomic assemblies from sorghum and maize. Although these gene copies are preserved on both chromosomes, their expression patterns have diverged. When the gene order of rice chromosomes 11 and 12 was compared to wheat gene loci, significant synteny between these orthologous regions was detected, illustrating the presence of conserved genes alternating with recently evolved genes. CONCLUSION: Because the resistance and defense response genes, enriched on these chromosomes relative to the whole genome, also occur in clusters, they provide a preferred target for breeding durable disease resistance in rice and the isolation of their allelic variants. The recent duplication of a large chromosomal segment coupled with the high density of disease resistance gene clusters makes this the most recently evolved part of the rice genome. Based on syntenic alignments of these chromosomes, rice chromosome 11 and 12 do not appear to have resulted from a single whole-genome duplication event as previously suggested.

Chromosome Mapping↗
PubMed2005

Characterization of the LARGE family of putative glycosyltransferases associated with dystroglycanopathies.

The Large(myd) mouse has a loss-of-function mutation in the putative glycosyltransferase gene Large. Mutations in the human homolog (LARGE) have been described in a form of congenital muscular dystrophy (MDC1D). Other genes (POMT1, POMGnT1, fukutin, and FKRP) that encode known or putative glycosylation enzymes are also causally associated with human congenital muscular dystrophies. All these diseases are associated with hypoglycosylation of the membrane protein alpha-dystroglycan (alpha-DG) and consequent loss of extracellular ligand binding. Hence, they are termed dystroglycanopathies. A paralogous gene for LARGE (LARGE2 or GYLTL1B) may also have a role in DG glycosylation. Using database interrogation and reverse-transcriptase polymerase chain reaction (RT-PCR), we identified vertebrate orthologs of each of these LARGE genes in many vertebrates, including human, mouse, dog, chicken, zebrafish, and pufferfish. However, within invertebrate genomes, we were able to identify only single homologs. We suggest that vertebrate LARGE orthologs be referred to as LARGE1. RT-PCR, dot-blot, and northern analysis indicated that LARGE2 has a more restricted tissue-expression profile than LARGE1. Using epitope-tagged proteins, we show that both LARGE1 and LARGE2 localize to the Golgi apparatus. The high similarity between the LARGE paralogs suggests that LARGE2 may also act on DG. Overexpression of LARGE2 in mouse C2C12 myoblasts results in increased glycosylation of alpha-DG accompanied by an increase in laminin binding. Thus, there may be functional redundancy between LARGE1 and LARGE2. Consistent with this idea, we show that alpha-DG is still fully glycosylated in kidney (a tissue that expresses a high level of LARGE2 mRNA) of Large(myd) mutant mice.

Alternative Splicing↗
PubMed2006

Evolutionary history of the Asr gene family.

The Asr gene family is widespread in higher plants. Most Asr genes are up-regulated under different environmental stress conditions and during fruit ripening. ASR proteins are localized in the nucleus and their likely function is transcriptional regulation. In cultivated tomato, we identified a novel fourth family member, named Asr4, which maps close to its sibling genes Asr1-Asr2-Asr3 and displays an unshared region coding for a domain containing a 13-amino acid repeat. In this work we were able to expand our previous analysis for Asr2 and investigated the coding regions of the four known Asr paralogous genes in seven tomato species from different geographic locations. In addition, we performed a phylogenetic analysis on ASR proteins. The first conclusion drawn from this work is that tomato ASR proteins cluster together in the tree. This observation can be explained by a scenario of concerted evolution or birth and death of genes. Secondly, our study showed that Asr1 is highly conserved at both replacement and synonymous sites within the genus Lycopersicon. ASR1 protein sequence conservation might be associated with its multiple functions in different tissues while the low rate of synonymous substitutions suggests that silent variation in Asr1 is selectively constrained, which is probably related to its high expression levels. Finally, we found that Asr1 activation under water stress is not conserved between Lycopersicon species.

Amino Acid Sequence↗
PubMed2004

A gene cluster for secondary metabolism in oat: implications for the evolution of metabolic diversity in plants.

The evolution of the ability to synthesize specialized metabolites is likely to have been key for survival and diversification of different plant species. Oats (Avena spp.) produce antimicrobial triterpenoids (avenacins) that protect against disease. The oat beta-amyrin synthase gene AsbAS1, which encodes the first committed enzyme in the avenacin biosynthetic pathway, is clearly distinct from other plant beta-amyrin synthases. Here we show that AsbAS1 has arisen by duplication and divergence of a cycloartenol synthase-like gene, and that its properties have been refined since the divergence of oats and wheat. Strikingly, we have also found that AsbAS1 is clustered with other genes required for distinct steps in avenacin biosynthesis in a region of the genome that is not conserved in other cereals. Because the components of this gene cluster are required for at least four clearly distinct enzymatic processes (2,3-oxidosqualene cyclization, beta-amyrin oxidation, glycosylation, and acylation), it is unlikely that the cluster has arisen as a consequence of duplication of a common ancestor. Although clusters of paralogous genes are common in plants (e.g., gene clusters for rRNA and specific disease resistance), reports of clusters of genes that do not share sequence relatedness and whose products contribute to a single selectable function are rare [Gierl, A. & Frey, M. (2001) Planta 213, 493-498]. Taken together, our evidence has important implications for the generation of metabolic diversity in plants.

Acylation↗
PubMed2003

Purification of the Arabidopsis 26 S proteasome: biochemical and molecular analyses revealed the presence of multiple isoforms.

The 26 S proteasome is a multisubunit protease complex responsible for degrading a wide range of intracellular proteins in eukaryotes, especially those modified with polyubiquitin chains. It is composed of a self-compartmentalized core protease (CP) that houses the peptidase active sites appended on either or both ends by a regulatory particle (RP) that identifies appropriate substrates and translocates them into the lumen of the CP for breakdown. Here, we describe the molecular and biochemical properties of the 26 S proteasome from the plant Arabidopsis thaliana. Like the CP and the ATPase ring of the RP, the RP non-ATPase subunits are often encoded by two transcriptionally active genes with some pairs displaying sufficient sequence divergence to suggest functional differences. Most RPN subunits could functionally replace their yeast counterparts, implying that they have retained their positions and activities within the complex. A method was developed to purify the 26 S proteasome intact from whole Arabidopsis seedlings. These preparations are biochemically indistinguishable from those from yeast and mammals, including the need for ATP to maintain integrity and a strong sensitivity to the inhibitors MG115, MG132, lactacystin, and epoxomicin. Mass spectrometric analysis of the complex detected the presence of almost all CP and RP subunits. In many cases, both products of paralogous genes were detected, demonstrating that each isoform assembles into the mature particle. As with the yeast and animal 26 S proteasomes, attenuation of individual RP genes induces a coordinated up-regulation of many of the other 26 S proteasome genes, suggesting that plants contain a negative feedback mechanism to regulate the 26 S proteasome levels. The incorporation of paralogous subunits into the Arabidopsis holoprotease raises the intriguing possibility that plants synthesize multiple 26 S proteasome types with unique properties and/or target specificities.

Adenosine Triphosphatases↗
PubMed1997

Canalization: a molecular genetic perspective.

The phenomenon of canalization--the genetic capacity to buffer developmental pathways against mutational or environmental perturbations--was first characterized in the late 1930s and early 1940s. Despite enormous subsequent progress in understanding the nature of the genetic material and the molecular basis of gene expression, there have been few attempts to interpret the classical work on canalization in molecular genetic terms. Some recent findings, however, bear on one form of canalization, 'genetic canalization', the stabilization of development against mutational effects. These data indicate that co-expressed paralogous genes can function as mutual 'back-up' elements in developmental processes. Paralogues, however, are far from the only basis of canalization: other genetic sources can be readily envisaged and some of these are described here. The evolutionary questions about genetic canalization and the mechanistic questions about developmental instability that still need to be addressed are also briefly discussed.

Animals↗
PubMed2006

BodyMap-Xs: anatomical breakdown of 17 million animal ESTs for cross-species comparison of gene expression.

BodyMap-Xs (http://bodymap.jp) is a database for cross-species gene expression comparison. It was created by the anatomical breakdown of 17 million animal expressed sequence tag (EST) records in DDBJ using a sorting program tailored for this purpose. In BodyMap-Xs, users are allowed to compare the expression patterns of orthologous and paralogous genes in a coherent manner. This will provide valuable insights for the evolutionary study of gene expression and identification of a responsive motif for a particular expression pattern. In addition, starting from a concise overview of the taxonomical and anatomical breakdown of all animal ESTs, users can navigate to obtain gene expression ranking of a particular tissue in a particular animal. This method may lead to the understanding of the similarities and differences between the homologous tissues across animal species. BodyMap-Xs will be automatically updated in synchronization with the major update in DDBJ, which occurs periodically.

Animal Structures↗
PubMed2006

MAP-ping genomic organization and organ-specific expression profiles of poplar MAP kinases and MAP kinase kinases.

BACKGROUND: As in other eukaryotes, plant mitogen-activated protein kinase (MAPK) cascades are composed of three classes of hierarchically organized protein kinases, namely MAPKKKs, MAPKKs, and MAPKs. These modules rapidly amplify and transduce extracellular signals into various appropriate intracellular responses. While extensive work has been conducted on the post-translational regulation of specific MAPKKs and MAPKs in various plant species, there has been no systematic investigation of the genomic organization and transcriptional regulation of these genes. RESULTS: Ten putative poplar MAPKK genes (PtMKKs) and 21 putative poplar MAPK genes (PtMPKs) have been identified and located within the poplar (Populus trichocarpa) genome. Analysis of exon-intron junctions and of intron phase inside the predicted coding region of each candidate gene has revealed high levels of conservation within and between phylogenetic groups. Expression profiles of all members of these two gene families were also analyzed in 17 different poplar organs, using gene-specific primers directed at the 3'-untranslated region of each candidate gene and real-time quantitative PCR. Most PtMKKs and PtMPKs were differentially expressed across this developmental series. CONCLUSION: This analysis provides a complete survey of MAPKK and MAPK gene expression profiles in poplar, a large woody perennial plant, and thus complements the extensive expression profiling data available for the herbaceous annual Arabidopsis thaliana. The poplar genome is marked by extensive segmental and chromosomal duplications, and within both kinase families, some recently duplicated paralogous gene pairs often display markedly different patterns of expression, consistent with the rapid evolution of specialized protein functions in this highly adaptive species.

3' Untranslated Regions↗
PubMed2006

The hmuQ and hmuD genes from Bradyrhizobium japonicum encode heme-degrading enzymes.

Utilization of heme by bacteria as a nutritional iron source involves the transport of exogenous heme, followed by cleavage of the heme macrocycle to release iron. Bradyrhizobium japonicum can use heme as an iron source, but no heme-degrading oxygenase has been described. Here, bioinformatics analyses of the B. japonicum genome identified two paralogous genes renamed hmuQ (bll7075) and hmuD (bll7423) that encode proteins with weak similarity to the heme-degrading monooxygenase IsdG from Staphylococcus aureus. The hmuQ gene is clustered with known heme transport genes in the genome. Recombinant HmuQ bound heme with a K(d) value of 0.8 microM and showed spectral properties consistent with a heme oxygenase. In the presence of a reductant, HmuQ catalyzed the degradation of heme and the formation of biliverdin. The hmuQ and hmuD genes complemented a Corynebacterium ulcerans heme oxygenase mutant in trans for utilization of heme as the sole iron source for growth. Furthermore, homologs of hmuQ and hmuD were identified in many bacterial genera, and the recombinant homolog from Brucella melitensis bound heme and catalyzed its degradation. The findings show that hmuQ and hmuD encode heme oxygenases and indicate that the IsdG family of heme-degrading monooxygenases is not restricted to gram-positive pathogenic bacteria.

Amino Acid Sequence↗
PubMed2004

Identification of 24 genes and two pseudogenes coding for olfactory receptors in Japanese loach, classified into four subfamilies: a putative evolutionary process for fish olfactory receptor genes by comprehensive phylogenetic analysis.

Twenty-four olfactory receptor (OR) genes and two pseudogenes have been identified in the genome of Japanese loach (Misgurnus anguillicaudatus). The genes were classified into four subfamilies according to the similarity of the amino acid sequences. In each subfamily, members showed high sequence similarity not only to each other but also to orthologues of other fish species. The number of members in each OR subfamily was roughly estimated to be from 3 to 10 by genomic Southern blot analysis. The genes of all four OR subfamilies were shown to express on olfactory neurons of the olfactory epithelium by in situ hybridization analysis. Two major features of fish OR genes were found by comprehensive and comparative analyses on OR genes of Japanese loach and other fish species including catfish, zebrafish and pufferfish. First, the phylogenetic tree comprising of representative subfamily members suggests the existence of several prototype genes common to the genomes of many fish species. Second, when all members of orthologous subfamilies identified in each clade of the tree are integrated, the members of a single species comprise a monophyletic group. This means that 'intraspecies' sequence homology, that is, homology among paralogous genes of the same subfamily in a species, is higher than 'interspecies' homology, that is, homology between orthologous genes of different species. This suggests that the subfamily members of a species have evolved recently. Taken together, fish OR genes have evolved from a limited number of prototype genes common to most fish species, and several genes in a subfamily have diversely evolved in each species from each prototype.

Amino Acid Sequence↗
PubMed2006

A dual-genome microarray for the pea aphid, Acyrthosiphon pisum, and its obligate bacterial symbiont, Buchnera aphidicola.

BACKGROUND: The best studied insect-symbiont system is that of aphids and their primary bacterial endosymbiont Buchnera aphidicola. Buchnera inhabits specialized host cells called bacteriocytes, provides nutrients to the aphid and has co-speciated with its aphid hosts for the past 150 million years. We have used a single microarray to examine gene expression in the pea aphid, Acyrthosiphon pisum, and its resident Buchnera. Very little is known of gene expression in aphids, few studies have examined gene expression in Buchnera, and no study has examined simultaneously the expression profiles of a host and its symbiont. Expression profiling of aphids, in studies such as this, will be critical for assigning newly discovered A. pisum genes to functional roles. In particular, because aphids possess many genes that are absent from Drosophila and other holometabolous insect taxa, aphid genome annotation efforts cannot rely entirely on homology to the best-studied insect systems. Development of this dual-genome array represents a first attempt to characterize gene expression in this emerging model system. RESULTS: We chose to examine heat shock response because it has been well characterized both in Buchnera and in other insect species. Our results from the Buchnera of A. pisum show responses for the same gene set as an earlier study of heat shock response in Buchnera for the host aphid Schizaphis graminum. Additionally, analyses of aphid transcripts showed the expected response for homologs of known heat shock genes as well as responses for several genes with unknown functional roles. CONCLUSION: We examined gene expression under heat shock of an insect and its bacterial symbiont in a single assay using a dual-genome microarray. Further, our results indicate that microarrays are a useful tool for inferring functional roles of genes in A. pisum and other insects and suggest that the pea aphid genome may contain many gene paralogs that are differentially regulated.

Animals↗
PubMed2004

The homeobox genes ATHB12 and ATHB7 encode potential regulators of growth in response to water deficit in Arabidopsis.

The Arabidopsis thaliana homeodomain leucine-zipper gene ATHB7 , which is active specifically under water deficit conditions, is proposed to act as a negative regulator of growth (Soderman et al ., 1996, Plant J. 10: 375 381; Hjellstrom et al ., 2003, Plant Cell Environ 26: 1127 1136). In this report we demonstrate that the paralogous gene, ATHB12 , has a similar expression pattern and function. ATHB12 ,like ATHB7 ,was up-regulated during water deficit conditions, the up-regulation being dependent on abscisic acid (ABA) and on the activity of the Ser/Thr phosphatases ABI1 and ABI2. Plants that are mutant for ATHB12 , as a result of T-DNA insertions in the ATHB12 gene, showed a reduced sensitivity to ABA in root elongation assays, whereas transgenic Arabidopsis plants expressing ATHB12 and/or ATHB7 as driven by the CaMV 35S promoter were hypersensitive in this response compared to wild-type. High-level expression of either gene also resulted in a delay in inflorescence stem elongation growth and caused plants to develop rosette leaves with a more rounded shape, shorter petioles, and increased branching of the inflorescence stem. Transgenic Arabidopsis plants expressing the reporter gene uidA under the control of the ATHB12 promoter showed marker gene activity in axillary shoot primordia, lateral root primordia, inflorescence stems and in flower organs. Treatment of plants with ABA or water deficit conditions caused the activity of ATHB12 to increase in the inflorescence stem, the flower organs and the leaves, and to expand into the vasculature of roots and the differentiation/elongation zone of root tips. Taken together, these results indicate that ATHB12 and ATHB7 act to mediate a growth response to water deficit by similar mechanisms.

Abscisic Acid↗
PubMed1993

Different modes of Mhc evolution in primates.

The human major histocompatibility complex (Mhc) is a chromosomal segment approximately 4 million bp long that contains > or = 84 genes. Some of these genes code for the class I and class II molecules, while the remaining genes code for complement components, cytochrome P450, tumor necrosis factor, and many other, unrelated proteins. We demonstrate on three examples (DP, C4-CYP21, and DRB) that different regions of the Mhc have different evolutionary histories. The organization of the DP region, which in humans contains four genes, was established in the ancestral Anthropoidea or earlier and has not changed since. The duplication that generated the two C4-CYP21 modules occurred in the ancestral Catarrhini or earlier, but the region has been undergoing periodic homogenizations via unequal crossing-over, which make paralogous genes in the same species more similar to each other than to orthologous genes of different species. The eight or nine genes of the DRB region were also generated in the ancestral Catarrhini, but the region has since been subject to frequent rearrangements, which generated various DRB haplotypes. Not only the alleles but, in part, also the haplotype polymorphism is evolving transspecifically. The DRB region of the Platyrrhini has an origin different from that of the Catarrhini. The picture emerging from these studies is that of both stability in some regions of the Mhc and tremendous evolutionary instability in other regions.

Animals↗
PubMed2003

The phylogenetic position of red algae revealed by multiple nuclear genes from mitochondria-containing eukaryotes and an alternative hypothesis on the origin of plastids.

Red algae are one of the main photosynthetic eukaryotic lineages and are characterized by primitive features, such as a lack of flagella and the presence of phycobiliproteins in the chloroplast. Recent molecular phylogenetic studies using nuclear gene sequences suggest two conflicting hypotheses (monophyly versus non-monophyly) regarding the relationships between red algae and green plants. Although kingdom-level phylogenetic analyses using multiple nuclear genes from a wide-range of eukaryotic lineages were very recently carried out, they used highly divergent gene sequences of the cryptomonad nucleomorph (as the red algal taxon) or incomplete red algal gene sequences. In addition, previous eukaryotic phylogenies based on nuclear genes generally included very distant archaebacterial sequences (designated as the outgroup) and/or amitochondrial organisms, which may carry unusual gene substitutions due to parasitism or the absence of mitochondria. Here, we carried out phylogenetic analyses of various lineages of mitochondria-containing eukaryotic organisms using nuclear multigene sequences, including the complete sequences from the primitive red alga Cyanidioschyzon merolae. Amino acid sequence data for two concatenated paralogous genes (alpha- and beta-tubulin) from mitochondria-containing organisms robustly resolved the basal position of the cellular slime molds, which were designated as the outgroup in our phylogenetic analyses. Phylogenetic analyses of 53 operational taxonomic units (OTUs) based on a 1525-amino-acid sequence of four concatenated nuclear genes (actin, elongation factor-1alpha, alpha-tubulin, and beta-tubulin) reliably resolved the phylogeny only in the maximum parsimonious (MP) analysis, which indicated the presence of two large robust monophyletic groups (Groups A and B) and the basal eukaryotic lineages (red algae, true slime molds, and amoebae). Group A corresponded to the Opisthokonta (Metazoa and Fungi), whereas Group B included various primary and secondary plastid-containing lineages (green plants, glaucophytes, euglenoids, heterokonts, and apicomplexans), Ciliophora, Kinetoplastida, and Heterolobosea. The red algae represented the sister lineage to Group B. Using 34 OTUs for which essentially the entire amino acid sequences of the four genes are known, MP, distance, quartet puzzling, and two types of maximum likelihood (ML) calculations all robustly resolved the monophyly of Group B, as well as the basal position of red algae within eukaryotic organisms. In addition, phylogenetic analyses of a concatenated 4639-amino-acid sequence for 12 nuclear genes (excluding the EF-2 gene) of 12 mitochondria-containing OTUs (including C. merolae) resolved a robust non-sister relationship between green plants and red algae within a robust monophyletic group composed of red algae and the eukaryotic organisms belonging to Group B. A new scenario for the origin and evolution of plastids is suggested, based on the basal phylogenetic position of the red algae within the large clade (Group B plus red algae). The primary plastid endosymbiosis likely occurred once in the common ancestor of this large clade, and the primary plastids were subsequently lost in the ancestor(s) of the Discicristata (euglenoids, Kinetoplastida, and Heterolobosea), Heterokontophyta, and Alveolata (apicomplexans and Ciliophora). In addition, a new concept of "Plantae" is proposed for phototrophic and nonphototrophic organisms belonging to Group B and red algae, on the basis of the common history of the primary plastid endosymbiosis. The Plantae include primary plastid-containing phototrophs and nonphototrophic eukaryotes that possibly contain genes of cyanobacterial origin acquired in the primary endosymbiosis.

Cell Nucleus↗
PubMed2002

Physical mapping and characterization of the human Na,K-ATPase isoform, ATP1A4.

Four isoforms of the catalytic alpha subunit of the Na,K-ATPase have been previously identified. We characterized and mapped a genomic copy of the human ATP1A4 isoform between D1S2707 and WI-9524, telomeric to a nearby isoform ATP1A2, and within a candidate region at 1q23 for familial hemiplegic migraine (FHM). Human ATP1A4 gene shares 84% identity with the mouse Atp1a4 gene, and both consist of 22 exons and 21 introns. The predicted polypeptide is 1029 amino acids and shares 82 and 79.8% identity, respectively, with human ATP1A2 and ATP1A1. ATP1A4 is larger than other isoforms and most divergent at the N-terminus. ATP1A4 and ATP1A2 are paralogous genes with the same number and organization of putative H-transmembrane domains, conserved exon-intron boundaries, and are found approximately 8.5 kb apart. Expression analysis of the ATP1A4 gene revealed a new major approximately 7.5 kb transcript in human skeletal muscle, with expression also shown in mouse muscle. Predictive analysis of promoter regions identified muscle specific regulatory elements for ATP1A4 and Atp1a4. Mutation analysis among eight affected individuals from a single large, highly penetrant FHM family was negative in ATP1A4 and ATP1A2 although multiple polymorphisms were identified.

Amino Acid Sequence↗
PubMed2005

Two distinct genes drive expression of seven tomosyn isoforms in the mammalian brain, sharing a conserved structure with a unique variable domain.

Tomosyn was previously identified as a syntaxin-binding protein that inhibits soluble NSF (n-ethylmaleimide-sensitive fusion protein) attachment protein receptor (SNARE)-mediated secretion. We set out to investigate the distribution of tomosyn mRNA in the mammalian brain and found evidence for the presence of two paralogous genes designated tomosyn-1 and -2. In a collection of tomosyn-2 cDNA clones, we observed four splice variants (named xb-, b-, m- and s-tomosyn-2) derived from the skipping of exons 19 and 21. This feature is conserved with tomosyn-1 that encodes three splice variants. To compare the expression pattern of tomosyn-1 and -2, we performed in situ hybridization experiments with gene-specific probes. Both genes were expressed in the nervous system, clearly following distinct spatial and developmental expression patterns. Real-time quantitative PCR experiments indicated that tomosyn-1 expression was up-regulated less than threefold between developmental stages E10 and P12, whereas tomosyn-2 expression increased 31-fold. Not only the transcription level, but also the splice composition of tomosyn-2 mRNA shifted during development. We conclude that two distinct genes drive expression of seven tomosyn isoforms. Their expression patterns support a role in regulating neuronal secretion. All isoforms share conserved WD40 and SNARE domains separated by a hypervariable module, the function of which remains to be clarified.

Adaptor Proteins, Vesicular Transport↗
PubMed1999

KEGG: Kyoto Encyclopedia of Genes and Genomes.

Kyoto Encyclopedia of Genes and Genomes (KEGG) is a knowledge base for systematic analysis of gene functions in terms of the networks of genes and molecules. The major component of KEGG is the PATHWAY database that consists of graphical diagrams of biochemical pathways including most of the known metabolic pathways and some of the known regulatory pathways. The pathway information is also represented by the ortholog group tables summarizing orthologous and paralogous gene groups among different organisms. KEGG maintains the GENES database for the gene catalogs of all organisms with complete genomes and selected organisms with partial genomes, which are continuously re-annotated, as well as the LIGAND database for chemical compounds and enzymes. Each gene catalog is associated with the graphical genome map for chromosomal locations that is represented by Java applet. In addition to the data collection efforts, KEGG develops and provides various computational tools, such as for reconstructing biochemical pathways from the complete genome sequence and for predicting gene regulatory networks from the gene expression profiles. The KEGG databases are daily updated and made freely available (http://www.genome.ad.jp/kegg/).

Animals↗