RFLPs detected with the human TCP10 gene, a homologue of a mouse t-complex gene.
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Animals↗
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Results for “t-Complex Genome Region”
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Molecular evidence for the rapid propagation of mouse t haplotypes from a single, recent, ancestral chromosome.
Mouse t haplotypes are variant forms of chromosome 17 that exist at high frequencies in worldwide populations of two species of commensal mice. To determine both the relationship of t haplotypes to each other and the species within which they exist, 35 representative t haplotypes were analyzed by means of 10 independent molecular probes, including five DNA clones and five polypeptide spots identified by means of two-dimensional gel electrophoresis. All of the tested haplotypes were found to share restriction fragments and polypeptide spots that are absent in mice carrying wild-type forms of chromosome 17. This observation provides the first direct evidence that all of the known t haplotypes are descendents of a single ancestral chromosome. The absence of variation among t haplotypes could mean that this ancestral chromosome existed relatively recently, in which case it would be necessary to postulate introgressions of t haplotypes across species lines to explain their presence in both Mus domesticus and M. musculus. Alternatively, it is possible that the ancestral chromosome existed prior to the split between M. domesticus and M. musculus and that, by chance, our probes fail to detect polymorphisms that exist among the t haplotypes. A further result of our analysis is the characterization of a partial t haplotype in a wild population of Israeli mice.
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Phylogenetic distribution in the genus Mus of t-complex-specific DNA and protein markers: inferences on the origin of t-haplotypes.
We have examined the phylogenetic distribution of two t-specific markers among representatives of various taxa belonging to the genus Mus. The centromeric TCP-1a marker (a testicular protein variant specific for all t-haplotypes so far studied) has also been apparently detected in several non-t representatives of the Mus IVA, Mus IVB, and probably M. cervicolor species. By contrast, a t-specific restriction-fragment-length polymorphism allele (RFLP) of the telomeric alpha-globin pseudogene DNA marker alpha-psi-4 was found only in animals belonging to the M. musculus-complex species either bearing genuine t-haplotypes or, like the M. m. bactrianus specimen studied here, likely to do so. This t-specific alpha-psi-4 RFLP allele was found to be as divergent from the RFLP alleles of the latter, non-t, taxonomical groups as it is from Mus 4A, Mus 4B, or M. spretus ones. These results suggest the presence of t-haplotypes and of t-specific markers in populations other than those belonging to the M. m. domesticus and M. m. musculus subspecies, implying a possible origin for t-haplotypes prior to the radiation of the most recent offshoot of the Mus genus (i.e., the spretus/domesticus divergence), some 1-3 Myr ago.
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Restriction fragment length polymorphisms at the porcine t complex polypeptide 1 (TCP1) locus.
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Animals↗
Evolution of the chaperonin families (Hsp60, Hsp10 and Tcp-1) of proteins and the origin of eukaryotic cells.
The members of the 10 kDa and 60 kDa heat-shock chaperonin proteins (Hsp10 and Hsp60 or Cpn10 and Cpn60), which form an operon in bacteria, are present in all eubacteria and eukaryotic cell organelles such as mitochondria and chloroplasts. In archaebacteria and eukaryotic cell cytosol, no close homologues of Hsp10 or Hsp60 have been identified. However, these species (or cell compartments) contain the Tcp-1 family of proteins (distant homologues of Hsp60). Phylogenetic analysis based on global alignments of Hsp60 and Hsp10 sequences presented here provide some evidence regarding the evolution of mitochondria from a member of the alpha-subdivision of Gram-negative bacteria and chloroplasts from cyanobacterial species, respectively. This interference is strengthened by the presence of sequence signatures that are uniquely shared between Hsp60 homologues from alpha-purple bacteria and mitochondria on one hand, and the chloroplasts and cyanobacterial hsp60s on the other. Within the alpha-purple subdivision, species such as Rickettsia and Ehrlichia, which live intracellularly within eukaryotic cells, are indicated to be the closest relatives of mitochondrial homologues. In the Hsp60 evolutionary tree, rooted using the Tcp-1 homologue, the order of branching of the major groups was as follows: Gram-positive bacteria--cyanobacteria and chloroplasts--chlamydiae and spirochaetes--beta- and gamma-Gram-negative purple bacteria--alpha-purple bacteria--mitochondria. A similar branching order was observed independently in the Hsp10 tree. Multiple Hsp60 homologues, when present in a group of species, were found to be clustered together in the trees, indicating that they evolved by independent gene-duplication events. This review also considers in detail the evolutionary relationship between Hsp60 and Tcp-1 families of proteins based on two different models (viz. archaebacterial and chimeric) for the origin of eukaryotic cell nucleus. Some predictions of the chimeric model are also discussed.
Amino Acid Sequence↗
The thermosome of Thermoplasma acidophilum and its relationship to the eukaryotic chaperonin TRiC.
A high molecular-mass protein complex from the archaebacterium Thermoplasma acidophilum, referred to here as the 'thermosome', is built from two subunits (M(r) 58 and 60). The thermosome has been purified to homogeneity. The molecular mass of the native complex was determined to be 1061 +/- 30 Da by scanning transmission electron microscopy. It shows a weak ATPase activity and is able to bind denatured polypeptides. Averages obtained from electron micrographs of negatively stained molecules in the end-on and side-on orientations, respectively, were compared with those of the t-complex polypeptide 1 ring complex (TRiC), isolated from bovine testes. Both molecules consist of two stacked pseudo eightfold symmetric rings which build up a cylindrical particle with a large cavity in the center. Sequence alignments of peptides generated from both subunits of the thermosome and different subunits of TRiC reveal a high partial similarity to each other and to the archaebacterial chaperonin thermophilic factor 55 from Sulfolobus shibatae as well as to eukaryotic TCP1 proteins. These striking structural similarities confirm the proposition that all these molecules belong to a single protein family which is structurally and functionally related to the GroEL class of molecular chaperones.
Adenosine Triphosphatases↗
The genetics of sperm function in fertilization.
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Animals↗
The yeast homolog to mouse Tcp-1 affects microtubule-mediated processes.
A Saccharomyces cerevisiae homolog to Drosophila melanogaster and mouse Tcp-1 encoding tailless complex polypeptide 1 (TCP1) has been identified, sequenced, and mapped. The mouse t complex has been under scrutiny for six decades because of its effects on embryogenesis and sperm differentiation and function. TCP1 is an essential gene in yeast cells and is located on chromosome 4R, linked to pet14. The TCP1-encoded proteins in yeast, Drosophila, and mouse cells share between 61 and 72% amino acid sequence identities, suggesting a primordial function for the TCP1 gene product. To assess function, we constructed a cold-impaired recessive mutation (tcp1-1) in the yeast gene. Cells carrying the tcp1-1 mutation grew linearly rather than exponentially at the restrictive temperature of 15 degrees C with a generation time of approximately 32 h in minimal medium. Both multinucleate and anucleate cells accumulated with time, suggesting that the linear growth kinetics may be explained by the generation of anucleate buds incapable of further cell division. In addition, the multinucleate and anucleate cells contained morphologically abnormal structures detected by anti-alpha-tubulin antibodies. The kinetics of appearance of these abnormalities suggest that they are a direct consequence of loss of function of the TCP1 protein and not a delayed, indirect consequence of cell death. We also observed that strains carrying tcp1-1 were hypersensitive to antimitotic compounds. Taken together, these observations imply that the TCP1 protein affects microtubule-mediated processes.
Amino Acid Sequence↗
Transient and restricted expression during mouse embryogenesis of Dll1, a murine gene closely related to Drosophila Delta.
The Drosophila Delta (Dl) gene is essential for cell-cell communication regulating the determination of various cell fates during development. Dl encodes a transmembrane protein, which contains tandem arrays of epidermal-growth-factor-like repeats in the extracellular domain and directly interacts with Notch, another transmembrane protein with similar structural features, in a ligand-receptor-like manner. Similarly, cell-cell interactions involving Delta-like and Notch-like proteins are required for cell fate determinations in C. elegans. Notch homologues were also isolated from several vertebrate species, suggesting that cell-to-cell signaling mediated by Delta- and Notch-like proteins could also underlie cell fate determination during vertebrate development. However, in vertebrates, no Delta homologues have yet been described. We have isolated a novel mouse gene, Dll1 (delta-like gene 1), which maps to the mouse t-complex and whose deduced amino acid sequence strongly suggests that Dll1 represents a mammalian gene closely related to Drosophila Delta. Dll1 is transiently expressed during gastrulation and early organogenesis, and in a tissue-restricted manner in adult animals. Between day 7 and 12.5 of development, expression was detected in the paraxial mesoderm, closely correlated with somitogenesis, and in subsets of cells in the nervous system. In adult animals, transcripts were detected in lung and heart. Dll1 expression in the paraxial mesoderm and nervous system is strikingly similar to the expression of mouse Notch1 during gastrulation and early organogenesis. The overlapping expression patterns of the Dll1 and Notch1 genes suggest that cells in these tissues can communicate by interaction of the Dll1 and Notch1 proteins. Our results support the idea that Delta- and Notch-like proteins are involved in cell-to-cell communication in mammalian embryos and suggest a role for these proteins in cellular interactions underlying somitogenesis and development of the nervous system.
Amino Acid Sequence↗
Sequence and structural homology between a mouse T-complex protein TCP-1 and the 'chaperonin' family of bacterial (GroEL, 60-65 kDa heat shock antigen) and eukaryotic proteins.
A mammalian cytoplasmic protein TCP-1, encoded by a gene within the mouse t-complex, has been found to exhibit highly significant (p much less than 0.00001) sequence homology to the 'chaperonin' family of bacterial and eukaryotic proteins (viz. groEL protein of E. coli, rubisco subunit binding protein of plant chloroplasts, yeast hsp58 and mammalian P1 proteins and 60-65 kDa mycobacterial antigen). With the introduction of few gaps, the amino acid sequence of TCP-1 shows between 60-63% similarity (17-20% identical residues and 42-45% conserved substitutions) throughout its length to various chaperonin proteins, indicating a common evolutionary origin. The sequence data also suggest that in contrast to the endosymbiotic origin of mitochondrial and chloroplast chaperonins, the cytoplasmic TCP-1 may have directly descended from the common universal ancestor via eukaryotic lineage. The observed similarity between TCP-1 and the 60-65 kDa bacterial 'common antigen' is also of importance from the viewpoint of immune/autoimmune response.
Amino Acid Sequence↗
Interaction of rat testis protein, TP, with nucleosome core particle.
Circular dichroism studies have revealed that addition of testis specific protein, TP in vitro, to rat testes nucleosome core particle resulted in a decrease in the compaction of the core particle DNA. This was also corroborated by thermal denaturation analysis. Addition of TP to nucleosome core particle resulted in the conversion of a biphasic transition towards a single phase. However, at the same time there was a 20% reduction in the overall hyperchromicity of core particle DNA at core particle to TP molar ratios of 1:2 and 1:3. These observations along with our earlier report, showing the DNA melting properties of TP, suggest that TP may play an important role in the disassembly process of nucleosome core particle during spermiogenesis.
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Characterization of a cDNA clone encoding a basic protein, TP2, involved in chromatin condensation during spermiogenesis in the mouse.
A cDNA clone encoding a small cysteine and serine-rich basic protein has been isolated from a mouse testis cDNA library. This cDNA clone encodes the mouse homologue of a protein involved in the initial phases of condensation of chromatin during spermiogenesis in rats, TP2, based on similarities in the sequence of the carboxyl terminus, composition, molecular weight, and electrophoretic mobility. Mouse TP2 can be divided into a highly basic domain comprising about one-third of the polypeptide chain at the carboxyl terminus and a much less basic domain comprising the remaining two-thirds at the amino terminus. The 5' end of the mouse TP2 mRNA contains two in-phase initiation codons both of which may be used generating two polypeptides which differ in length at the amino terminus. Southern blots demonstrate that there is a single copy of the TP2 gene in the mouse genome and Northern blots demonstrate that the polyadenylated TP2 mRNA is present at high and essentially equal levels in early and late haploid cells, and that it is virtually absent from meiotic cells.
Amino Acid Sequence↗
Identification of the major chromaffin granule-binding protein, chromobindin A, as the cytosolic chaperonin CCT (chaperonin containing TCP-1).
Chromobindin A is a multisubunit complex ATPase that binds to chromaffin granule membranes in a calcium-dependent manner and requires ATP for release from the membrane (Martin, W. H., and Creutz, C. E. (1987) J. Biol. Chem. 262, 2803-2810). Here we report that the seven previously characterized subunits of chromobindin A cross react with antisera specific to subunits of CCT, the chaperonin containing TCP-1 (Kubota, H., Hynes, G., Carne, A., Ashworth, A., and Willison, K. (1994) Curr. Biol. 4, 89-99). The chromobindin A subunits previously called chromobindins 12, 13, 14, 15, 16, 18, and 19 cross-react specifically with subunits beta, delta, theta, alpha, zeta, xi, and gamma, respectively, of CCT. Additional similarities in subunit molecular weights, isoelectric points, and the morphologies of the two protein complexes as determined by electron microscopy support identification of chromobindin A as an adrenal medullary form of CCT. The chromobindin A/CCT complex was found to bind at least 7-fold more efficiently to affinity columns of chromaffin granule membranes than of adrenal medullary cytosol proteins, suggesting a specific interaction occurs between the complex and membrane components. The results indicate that the previously described characteristics of chromobindin A are likely to be relevant to the functions of CCT and suggest that the adrenal medullary form of CCT may play a role in the activities of secretory vesicle membranes.
Animals↗
The human homologue of the mouse t-complex gene, TCP1, is located on chromosome 6 but is not near the HLA region.
Southern blot analysis indicates that there are four sequences in the human genome related to the mouse t-complex gene Tcp-1. All four genes were cloned and partial sequencing showed that one of them was a functional gene, and the other three were pseudogenes. The human sequences were all approximately 90% related to each other and 82-89% related to the mouse Tcp-1a sequence. Human TCP1 cDNA clones from both fibrosarcoma and B cell lines confirmed that there was a single expressed gene. mRNA transcripts of different sizes were accounted for by two different polyadenylation signals. The human TCP1 gene shared some amino acid substitutions with the mouse t-complex allele (Tcp-1a) which were not found in Tcp-1b. The functional human TCP1 gene was mapped, using a panel of somatic cell hybrids, as well as in situ analysis, to the long arm of chromosome 6 at 6q23-qter and thus is not closely linked to the HLA complex on the short arm. For this reason and others it is unlikely that there is a human equivalent of the mouse t-complex.
Amino Acid Sequence↗
Molecular clones of the mouse t complex derived from microdissected metaphase chromosomes.
Fragments of the proximal half of mouse chromosome 17 including the t-complex region were microdissected from metaphase spreads. DNA was isolated from a pool of such fragments, and was cloned on microscale. Individual clones were used to probe genomic digests of DNA from a pair of Chinese hamster cell lines with or without mouse chromosome 17, and livers of congenic inbred lines of mice carrying wild-type and/or t-haplotype forms of chromosome 17. The data obtained indicate that 95% of the low copy number microclone inserts recognize DNA sequences present on mouse chromosome 17. It has been possible to use one-third of these clones to identify restriction-fragment-length polymorphisms between wild-type and t-haplotype DNA on a congenic background. These results demonstrate that these clones have been derived from the t-complex or regions closely linked to it. Clones of this type should provide starting points for a molecular analysis of this region of the mouse genome.
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Yeast artificial chromosomes: an alternative approach to the molecular analysis of mouse developmental mutations.
Mammalian genetics now allows a molecular study of genomic regions previously analysed by genetic and embryological techniques. To simplify such an analysis, we have established a number of libraries of mouse DNA in Yeast Artificial Chromosome (YAC) vectors, constructed either by partial digestion with EcoRI, or by complete digestion with enzymes which cut rarely in the mammalian genome. In this paper we report the construction of complete digest libraries prepared from mouse genomic DNA using the rare cutter enzymes NotI and BssHII, and the detection of gene loci from the H-2 complex, the t-complex, and other loci from the mouse genome. Due to their large insert size, YAC clones simplify the cloning of extended regions of the mouse genome surrounding known developmental mutations and should, after introduction into the germ line, offer a high probability of correct expression of the genes contained within the cloned region. We hope that this will allow the use of YAC clones to scan regions of interest such as the t-complex for specific genes by testing DNA introduced into transgenic mice for the ability to complement mutations localised to this region.
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The mouse insulin-like growth factor type-2 receptor is imprinted and closely linked to the Tme locus.
T-associated maternal effect (Tme) is the only known maternal-effect mutation in the mouse. The defect is nuclear-encoded and embryos that inherit a deletion of the Tme locus from their mother die at day 15 of gestation. There are many genomically imprinted regions known in the mouse genome but so far no imprinted genes have been cloned. The Tme locus is absent in two chromosome-17 deletion mutants, Thp and the tLub2, and its position has been localized using these deletions to a 1-cM region. We report here that the genes for insulin-like growth factor type-2 receptor (Igf2r) and mitochondrial superoxide dismutase-2 (Sod-2) are absent from both deletions. Probes for these genes and for plasminogen (Plg) and T-complex peptide 1 (Tcp-1) were used in pulsed-field gel mapping to show that Tme must lie within a region of 800-1,100 kb. We also demonstrate that embryos express Igf2r only from the maternal chromosome, and that Tcp-1, Plg and Sod-2 are expressed from both chromosomes. Therefore Igf2r is imprinted and closely linked or identical to Tme.
Animals↗
Molecular organization of the D-Qa region of t-haplotypes suggests that recombination is an important mechanism for generating genetic diversity of the major histocompatibility complex.
We have determined the molecular maps of the H-2D and Qa regions of the t-complex haplotypes t12 and tw5 by chromosomal walking. Analysis with class I probes and other probes unique to the H-2D:Qa subregion indicates that the class I gene organization of t12 is: D1-D2-Q1-Q2-Q3-Qx-Q4-Q5-Q10, while that of tw5 is: D1-D2-Q1-Q2-Q4-Q5-Q10. Thus, the absence of the Q6-Q9 genes suggested previously in t-haplotypes was confirmed. A comparison of the molecular maps of the t12 and tw5 chromosomes revealed an extremely mosaic pattern of diversity: The regions between D1 and D2, and between Q4 and Q10, are very similar in both chromosomes. However, their Q1 to Q3 regions are strikingly different. Further comparisons of wild-type chromosomes and additional t-haplotypes by molecular mapping and genomic Southern blot hybridization with probes to the Q1-Q3 region showed a high level of polymorphism among both wild-type chromosomes and among t-haplotypes. The characteristics of the polymorphisms suggest that recombination may play an important role in generating this genetic diversity. Furthermore, recombination between wild-type and t-haplotype chromosomes may be involved.
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