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PubMed1992

Structural features and sites of expression of a new murine 65 kD and 48 kD hair-related keratin pair, associated with a special type of parakeratotic epithelial differentiation.

In the course of studies on local keratin phenotypes in the epidermis of the adult mouse, we have identified a new 65 kD and 48 kD keratin pair. In mouse skin, this keratin pair is only expressed in suprabasal cells of adult mouse tail scale epidermis which is characterized by the complete absence of a granular layer and the formation of a remarkably compact stratum corneum. A second site in which the 65 kD and 48 kD keratin pair is suprabasally expressed and whose morphology corresponds to that of tail scale epidermis is found in the posterior unit of the complex filiform papillae of mouse tongue. The causal relationship of the expression of the 65 kD and 48 kD keratins with this particular type of a non-pathological epithelial parakeratosis is emphasized by the suppression of the mRNA synthesis of the two keratins during retinoic acid mediated orthokeratotic conversion of tail scale epidermis. Apart from tail scale epidermis and the posterior unit of the filiform papillae, the 65 kD and 48 kD keratin pair is, however, also coexpressed with "hard" alpha keratins in suprabulbar cells of hair follicles and in suprabasal cells of the central core unit of the lingual filiform papillae. The non alpha-helical domains of the two new keratins are rich in cysteine and proline residues and lack the typical subdomains into which epithelial keratins of both types can be divided. This structural resemblance of the 65 kD and 48 kD keratins to "hard" alpha keratins is supported by comparative flexibility predictions for their non alpha-helical domains. Phylogenetic investigations then show that the 65 kD and 48 kD keratin pair has evolved together with hair keratins, but has diverged from these during evolution to constitute an independent branch of a pair of hair-related keratins. In view of this exceptional position of the 65 kD and 48 kD keratins within the keratin multigene family, their expression has apparently been adopted by rare anatomical sites in which an orthokeratinized stratum corneum would be too soft and a hard keratinized structure would be too rigid to meet the functional requirement of the respective epithelia.

Amino Acid Sequence↗

PubMed1984

Comparison of spectrin isolated from erythroid and non-erythroid sources.

Spectrin from erythrocytes and two other tissues (brain and intestine) were isolated from two distant species, pig and chicken; some structural and functional properties were compared. A quantitative antibody inhibition assay was used to determine that antibodies to mammalian red cell spectrin cross-react very poorly, if at all, with their non-erythroid (brain) counterpart and similarly antibodies to pig brain spectrin (fodrin) cross-react very weakly with erythroid spectrin. By contrast, antibodies which were directed against the 240000-Mr subunit of avian fodrin were completely inhibited with avian spectrin and vice versa. To analyze the structural relatedness of these molecules further we compared the chymotryptic iodinated peptide maps generated from each individual subunit. Consistent with the antibody results, we find little (less than 10%) homology between peptides derived from mammalian fodrin and spectrin, but complete homology (100%) of the peptides derived from the 240000-Mr subunits of chicken fodrin, spectrin and another related molecule from intestine, TW260/240. Whereas the peptide maps of fodrin (brain spectrin) revealed striking similarity between divergent species, suggesting a high degree of structural conservation, the peptide maps of erythrocyte spectrin was highly variable between species, indicating that it has diverged considerably in mammalian evolution. In addition we have compared a functional activity of mammalian spectrins, the ability to bind calmodulin, using two different assays. Both results show that, whereas fodrin-calmodulin interaction can be readily demonstrated, the binding to mammalian erythroid spectrin is negligible. This suggests that the high-affinity calmodulin site present on fodrin has been lost from spectrin in mammalian evolution.

Animals↗

PubMedDate not supplied

A new class and order of myxozoans to accommodate parasites of bryozoans with ultrastructural observations on Tetracapsula bryosalmonae (PKX organism).

Tetracapsula bryosalmonae, formerly PKX organism, is a myxozoan parasite that causes proliferative kidney disease in salmonid fish. Its primary hosts, in which it undergoes a sexual phase, are phylactolaemate bryozoans. It develops in the bryozoan coelomic cavity as freely floating sacs which contain two types of cells, stellate cells and sporoplasmogenic cells, which become organised as spores. Eight stellate cells differentiate as four capsulogenic cells and four valve cells which surround a single sporoplasmogenic cell. The sporoplasmogenic cell undergoes meiosis and cytoplasmic fission to produce two sporoplasms with haploid nuclei. Sporoplasms contain secondary cells. The unusual development supports previously obtained data from 18S rDNA sequences, indicating that species of Tetracapsula form a clade. It diverged early in the evolution of the Myxozoa, before the radiation that gave rise to the better known genera belonging to the two orders in the single class Myxosporea. The genus Tetracapsula as seen in bryozoans shares some of the characters unique to the myxosporean phase and others typical of the actinosporean phase of genera belonging to the class Myxosporea. However, it exhibits other features which are not found in either phase. A new class Malacosporea and order Malacovalvulida are proposed to accommodate the family Saccosporidae and genus Tetracapsula. Special features of the new class are the sac-like proliferative body, valve cells not covering the exit point of the polar filament, lack of a stopper-like structure sealing the exit, maintenance of valve cell integrity even at spore maturity, absence of hardened spore walls and unique structure of sporoplasmosomes in the sporoplasms.

Animals↗

PubMed1992

Growth-regulated expression of rhoG, a new member of the ras homolog gene family.

Cellular transition from the resting state to DNA synthesis involves master switches genes encoding transcriptional factors (e.g., fos, jun, and egr genes), whose targets remain to be fully characterized. To isolate coding sequences specifically accumulated in late G1, a differential screening was performed on a cDNA library prepared from hamster lung fibroblasts stimulated for 5 h with serum. One of the positive clones which displayed a sevenfold induction, turned out to code for a protein sharing homology to Ras-like products. Cloning and sequence analysis of the human homolog revealed that this putative new small GTPase, referred to as rhoG, is more closely related to the rac, CDC42, and TC10 members of the rho (ras homolog) gene family and might have diverged very early during evolution. rhoG mRNA accumulates in proportion to the mitogenic strength of various purified growth factors used for the stimulation, as a consequence of transcriptional activation. G1-specific RNA accumulation is impaired upon addition of antimitogenic cyclic AMP and is enhanced when protein synthesis is inhibited, mainly as a result of RNA stabilization. rhoG mRNA expression is observed in a wide variety of human organs but reaches a particularly high level in lung and placental tissues.

Amino Acid Sequence↗

PubMed1987

Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae.

Saccharomyces cerevisiae contains two genes which encode cyclic AMP (cAMP) phosphodiesterase. We previously isolated and characterized PDE2, which encodes a high-affinity cAMP phosphodiesterase. We have now isolated the PDE1 gene of S. cerevisiae, which encodes a low-affinity cAMP phosphodiesterase. These two genes represent highly divergent branches in the evolution of phosphodiesterases. High-copy-number plasmids containing either PDE1 or PDE2 can reverse the growth arrest defects of yeast cells carrying the RAS2(Val-19) mutation. PDE1 and PDE2 appear to account for the aggregate cAMP phosphodiesterase activity of S. cerevisiae. Disruption of both PDE genes results in a phenotype which resembles that induced by the RAS2(Val-19) mutation. pde1- pde2- ras1- ras2- cells are viable.

3',5'-Cyclic-AMP Phosphodiesterases↗

PubMed2006

Streamlining and simplification of microbial genome architecture.

The genomes of unicellular species, particularly prokaryotes, are greatly reduced in size and simplified in terms of gene structure relative to those of multicellular eukaryotes. Arguments proposed to explain this disparity include selection for metabolic efficiency and elevated rates of deletion in microbes, but the evidence in support of these hypotheses is at best equivocal. An alternative explanation based on fundamental population-genetic principles is proposed here. By increasing the mutational target sizes of associated genes, most forms of nonfunctional DNA are opposed by weak selection. Free-living microbial species have elevated effective population sizes, and the consequent reduction in the power of random genetic drift appears to be sufficient to enable natural selection to inhibit the accumulation of excess DNA. This hypothesis provides a potentially unifying explanation for the continuity in genomic scaling from prokaryotes to multicellular eukaryotes, the divergent patterns of mitochondrial evolution in animals and land plants, and various aspects of genomic modification in microbial endosymbionts.

Animals↗

PubMed2004

The evolution of drug-activated nuclear receptors: one ancestral gene diverged into two xenosensor genes in mammals.

BACKGROUND: Drugs and other xenobiotics alter gene expression of cytochromes P450 (CYP) by activating the pregnane X receptor (PXR) and constitutive androstane receptor (CAR) in mammals. In non-mammalian species, only one xenosensor gene has been found. Using chicken as a model organism, the aim of our study was to elucidate whether non-mammalian species only have one or two xenosensors like mammals. RESULTS: To explore the evolutionary aspect of this divergence, we tried to identify additional xenobiotic sensing nuclear receptors in chicken using various experimental approaches. However, none of those revealed novel candidates. Ablation of chicken xenobiotic receptor (CXR) function by RNAi or dominant-negative alleles drastically reduced drug-induction in a chicken hepatoma cell line. Subsequently, we functionally and structurally characterized CXR and compared our results to PXR and CAR. Despite the high similarity in their amino acid sequence, PXR and CAR have very distinct modes of activation. Some aspects of CXR function, e.g. direct ligand activation and high promiscuity are very reminiscent of PXR. On the other hand, cellular localization studies revealed common characteristics of CXR and CAR in terms of cytoplasmic-nuclear distribution. Finally, CXR has unique properties regarding its regulation in comparison to PXR and CAR. CONCLUSION: Our finding thus strongly suggest that CXR constitutes an ancestral gene which has evolved into PXR and CAR in mammals. Future studies should elucidate the reason for this divergence in mammalian versus non-mammalian species.

Journal Article↗

PubMed2006

Multiple, non-allelic, intein-coding sequences in eukaryotic RNA polymerase genes.

BACKGROUND: Inteins are self-splicing protein elements. They are translated as inserts within host proteins that excise themselves and ligate the flanking portions of the host protein (exteins) with a peptide bond. They are encoded as in-frame insertions within the genes for the host proteins. Inteins are found in all three domains of life and in viruses, but have a very sporadic distribution. Only a small number of intein coding sequences have been identified in eukaryotic nuclear genes, and all of these are from ascomycete or basidiomycete fungi. RESULTS: We identified seven intein coding sequences within nuclear genes coding for the second largest subunits of RNA polymerase. These sequences were found in diverse eukaryotes: one is in the second largest subunit of RNA polymerase I (RPA2) from the ascomycete fungus Phaeosphaeria nodorum, one is in the RNA polymerase III (RPC2) of the slime mould Dictyostelium discoideum and four intein coding sequences are in RNA polymerase II genes (RPB2), one each from the green alga Chlamydomonas reinhardtii, the zygomycete fungus Spiromyces aspiralis and the chytrid fungi Batrachochytrium dendrobatidis and Coelomomyces stegomyiae. The remaining intein coding sequence is in a viral relic embedded within the genome of the oomycete Phytophthora ramorum. The Chlamydomonas and Dictyostelium inteins are the first nuclear-encoded inteins found outside of the fungi. These new inteins represent a unique dataset: they are found in homologous proteins that form a paralogous group. Although these paralogues diverged early in eukaryotic evolution, their sequences can be aligned over most of their length. The inteins are inserted at multiple distinct sites, each of which corresponds to a highly conserved region of RNA polymerase. This dataset supports earlier work suggesting that inteins preferentially occur in highly conserved regions of their host proteins. CONCLUSION: The identification of these new inteins increases the known host range of intein sequences in eukaryotes, and provides fresh insights into their origins and evolution. We conclude that inteins are ancient eukaryote elements once found widely among microbial eukaryotes. They persist as rarities in the genomes of a sporadic array of microorganisms, occupying highly conserved sites in diverse proteins.

Alleles↗

PubMed2001

Protein-X, Pancreatic Stone-, Pancreatic thread-, reg-protein, P19, lithostathine, and now what? Characterization, structural analysis and putative function(s) of the major non-enzymatic protein of pancreatic secretions.

Reg protein was first found in pancreatic stones. It was named Pancreatic Stone Protein and later renamed lithostathine, as it was assumed to prevent stone formation. The 144 amino acid protein is O-glycosylated on Thr-5. The glycan chain is variable in length and in charge. Lithostathine 3-D organization is of the C-lectin type, even though it is unlikely to have any functional calcium-binding site. The Arg11-Ile12 bond is readily cleaved by trypsin; the resulting C-terminal polypeptide precipitates at physiological pH and tends to form fibrils. The protein was more recently found in the regenerating endocrine pancreas and it was named Reg (for regenerating) protein. Numerous proteins related to Reg have been identified successively in several mammalian species. They constitute the Reg superfamily. Reg genes show the same organization and are located in the same chromosome region. These genes are therefore likely to derive from a common ancestor gene by duplication. In the course of evolution, they may have diverged in tissue-related expression and function. In the endocrine pancreas, Reg protein stimulates islet beta-cell growth and reduces experimental diabetes via the activation of a high affinity receptor. The role of the protein produced by the exocrine pancreas, however, is controversial. Not only is Reg/lithostathine unlikely to be a physiologically relevant pancreatic stone inhibitor, but it may contribute to stone formation. We suggest that it might help prevent the harmful activation of protease precursors in the pancreatic juice. The protein provides a useful model for examining the conformational changes associated with globular to fibril transformation.

Amino Acid Sequence↗

PubMed2006

The cyclin-dependent kinase (CDK) family member PNQALRE/CCRK supports cell proliferation but has no intrinsic CDK-activating kinase (CAK) activity.

The cyclin-dependent kinases (CDKs) that drive the eukaryotic cell cycle must be phosphorylated within the activation segment (T-loop) by a CDK-activating kinase (CAK) to achieve full activity. Although a requirement for CDK-activating phosphorylation is conserved throughout eukaryotic evolution, CAK itself has diverged between metazoans and budding yeast, and fission yeast has two CAKs, raising the possibility that additional mammalian enzymes remain to be identified. We report here the characterization of PNQALRE (also known as CCRK or p42), a member of the mammalian CDK family most similar to the cell-cycle effectors Cdk1 and Cdk2 and to the CAK, Cdk7. Although PNQALRE/CCRK was recently proposed to activate Cdk2, we show that the monomeric protein has no intrinsic CAK activity. Depletion of PNQALRE by >80% due to RNA interference (RNAi) impairs cell proliferation, but fails to arrest the cell cycle at a discrete point. Instead, both the fraction of cells with a sub-G(1) DNA content and cleavage of poly(ADP-ribose) polymerase (PARP) increase. PNQALRE knockdown did not diminish Cdk2 T-loop phosphorylation in vivo or decrease CAK activity of a cell extract. In contrast, depletion of Cdk7 by RNAi causes a proportional decrease in the ability of an extract to activate recombinant Cdk2. Our data do not support the proposed function of PNQALRE/CCRK in activating CDKs, but instead reinforce the notion of Cdk7 as the major, and to date the only, CAK in mammalian cells.

Amino Acid Sequence↗

PubMed2001

Brachypodium distachyon. A new model system for functional genomics in grasses.

A new model for grass functional genomics is described based on Brachypodium distachyon, which in the evolution of the Pooideae diverged just prior to the clade of "core pooid" genera that contain the majority of important temperate cereals and forage grasses. Diploid ecotypes of B. distachyon (2n = 10) have five easily distinguishable chromosomes that display high levels of chiasma formation at meiosis. The B. distachyon nuclear genome was indistinguishable in size from that of Arabidopsis, making it the simplest genome described in grasses to date. B. distachyon is a self-fertile, inbreeding annual with a life cycle of less than 4 months. These features, coupled with its small size (approximately 20 cm at maturity), lack of seed-head shatter, and undemanding growth requirements should make it amenable to high-throughput genetics and mutant screens. Immature embryos exhibited a high capacity for plant regeneration via somatic embryogenesis. Regenerated plants display very low levels of albinism and have normal fertility. A simple transformation system has been developed based on microprojectile bombardment of embryogenic callus and hygromycin selection. Selected B. distachyon ecotypes were resistant to all tested cereal-adapted Blumeria graminis species and cereal brown rusts (Puccinia reconditia). In contrast, different ecotypes displayed resistance or disease symptoms following challenge with the rice blast pathogen (Magnaporthe grisea) and wheat/barley yellow stripe rusts (Puccinia striformis). Despite its small stature, B. distachyon has large seeds that should prove useful for studies on grain filling. Such biological characteristics represent important traits for study in temperate cereals.

Anti-Bacterial Agents↗

PubMed1976

[Histochemical characteristics of the lingual salivary glands of several classes of vertebrates].

The obtained results show that secretory elements of the tongue integuments submerged to the depth of the organ. It was accompanied by a formation and complication of terminal portions of the glands and their secretory pathways. In the process of evolution there occurred a divergence in the development of glandular cells from mucous ones in fishes through mucoserous and seromucous cells of amphibia and reptiles to mucous, seromucous and protein cells in the tongue glands of higher mammals. In mucous glands of terranian vertebrates, especially in mammals, the number of components in the composition of the produced secretion was found to increase.

Animals↗

PubMed2002

Folding pattern recognition in proteins using spectral analysis methods.

Divergence in sequence through evolution precludes sequence alignment based homology methodologies for protein folding prediction from detecting structural and folding similarities for distantly related protein. Homolog coverage of actual data bases is also a factor playing a critical role in the performance of those methodologies, the factor being conspicuously apparent in what is called the twilight zone of sequence homology in which proteins of high degree of similarity in both biological function and structure are found but for which the amino acid sequence homology ranges from about 20% to less than 30%. In contrast to these methodologies a strategy is proposed here based on a different concept of sequence homology. This concept is derived from a periodicity analysis of the physicochemical properties of the residues constituting proteins primary structures. The analysis is performed using a front-end processing technique in automatic speech recognition by means of which the cepstrum (measure of the periodic wiggliness of a frequency response) is computed that leads to a spectral envelope that depicts the subtle periodicity in physicochemical characteristics of the sequence. Homology in sequences is then derived by alignment of spectral envelopes. Proteins sharing common folding patterns and biological function but low sequence homology can then be detected by the similarity in spectral dimension. The methodology applied to protein folding recognition underscores in many cases other methodologies in the twilight zone.

Algorithms↗

PubMed1990

Tissue inhibitor of metalloproteinases-2 (TIMP-2) mRNA expression in tumor cell lines and human tumor tissues.

Human tissue inhibitor of metalloproteinase-2 (TIMP-2) was cloned and sequenced from an A2058 human melanoma cell cDNA library. When the sequence was compared with that of human TIMP-1 at both the nucleotide and deduced amino acid levels, the homology appeared closer at the protein level than at the nucleotide level, suggesting that these inhibitors diverged early in the evolution of this gene family. Comparison of the deduced amino acid sequence for TIMP-2 with that of human TIMP-1 shows that there are two regions in which the similarity is below the overall average of 66%. It is postulated that these regions are responsible for the unique ability of TIMP-2 to bind to the latent form of the 72-kDa type IV collagenase. Polyclonal anti-TIMP-2 antisera recognized TIMP-2 but not TIMP-1 on immunoblotting. Northern blot analysis of RNA from A2058 human melanoma, HT-144 human melanoma, HT-1080 human fibrosarcoma, and WI-38 fetal lung fibroblast cell lines demonstrated two distinct transcripts of 1.0 and 3.5 kilobases (kb) for timp-2 mRNA. Both transcripts are down-regulated in response to transforming growth factor-beta but are unchanged in response to phorbol ester treatment. This is in contrast to the up-regulation of timp-1 transcripts by these agents and indicates that timp-2 and timp-1 are independently regulated in cell culture. Northern blot analyses of matched normal and tumor tissue samples from five cases of human colorectal carcinoma were performed. Normal and tumor tissues contain both the 1.0- and 3.5-kb transcripts. However, in the tissue samples the ratio of the 3.5-kb transcript to the 1.0-kb transcript was markedly elevated. No evidence of down-regulation of timp-2 transcript levels was noted in the tumor tissues. This is in contrast to the elevated timp-1 transcript levels seen in these tumor samples. Thus, timp-2 mRNA transcript levels are differentially regulated from timp-1 levels in vivo as well as in cell culture.

Amino Acid Sequence↗

PubMed1988

The human genes for GM-CSF and IL 3 are closely linked in tandem on chromosome 5.

As demonstrated by long-range mapping of restriction endonuclease recognition sequences and genomic cloning, we found that the human genes encoding interleukin 3 (IL 3) and granulocyte/macrophage colony-stimulating factor (GM-CSF) are tandemly arrayed on the long arm of chromosome 5, separated by 9 kilobases (kb) of DNA. This close physical linkage of genes with similar structure and biologic function suggests that these cytokines may have evolved from a common ancestral gene. This linkage in evolution of two relatively divergent genes further implies that some of the other lymphokine and cytokine genes that appear to share as much or more sequence similarity than do IL 3 and GM-CSF may be distantly related members of a cytokine gene family.

Chromosome Mapping↗

PubMed1993

Splicing and 3'-processing of the tyrosine tRNA of Trypanosoma brucei.

Trypanosoma brucei belongs to a family of protozoa that is characterized as having diverged early in the evolution of eukaryotes. Many unusual forms of RNA processing have been discovered in these cells, one of which is trans-splicing, and, although a great number of genes have been sequenced, no evidence for cis-splicing has yet been found. This study shows that tRNA(Tyr) of T. brucei contains an 11-nucleotide intron. tRNA of the size predicted for unspliced precursor was detected by Northern analysis using an oligonucleotide probe complementary to the putative intervening region. Direct sequence analysis of mature tRNA(Tyr) showed that the predicted intron region is absent from this form of the molecule. Mutated versions of the gene encoding tRNA(Tyr) were introduced into trypanosomes by DNA transformation and shown to be expressed in vivo. Introduction into the genome of a tRNA(Tyr) gene containing an amber suppressor mutation led to a significant accumulation of unspliced precursor molecules. Analysis of the tRNA(Tyr) species from both the wild type and transformed cells revealed unspliced and spliced processing intermediates. The relative abundance of each of these intermediates suggests that 3'-processing and splicing occur independently and that, in the wild type, splicing tends to precede 3'-processing and CCA addition.

Animals↗

PubMed1996

Crystal structure of the human adenovirus proteinase with its 11 amino acid cofactor.

The three-dimensional structure of the human adenovirus-2 proteinase complexed with its 11 amino acid cofactor, pVIc, was determined at 2.6 A resolution by X-ray crystallographic analysis. The fold of this protein has not been seen before. However, it represents an example of either subtly divergent or powerfully convergent evolution, because the active site contains a Cys-His-Glu triplet and oxyanion hole in an arrangement similar to that in papain. Thus, the adenovirus proteinase represents a new, fifth group of enzymes that contain catalytic triads. pVIc, which extends a beta-sheet in the main chain, is distant from the active site, yet its binding increases the catalytic rate constant 300-fold for substrate hydrolysis. The structure reveals several potential targets for antiviral therapy.

Adenoviruses, Human↗

PubMed1997

[Molecular evolution of MHC DQA genes. I. The maintenance of interallelic divergence and the influence of GC content on gene structure].

The analyses of the proportion of synonymous and missense nucleotide substitution (PS and PN) in different exons, antigen recognition sites (ARS) and non-ARS of EN2 (NAEN2) of 23 alleles at MHC DQA loci in 7 mammal species gave rise to the following findings. (1) PN was about twice as much as PS in ARS among the alleles at DQA1 of any given species, i.e. 7 alleles at HLA-DQA1 or 8 alleles at IaAa this accords with overdominant selection; (2) PS showed more or less the same as PN in ARS among different loci (DQA1 or DQA2 in different species, or DQA1 and DQA2 in one species) or NAEN2 of all comparative pairs, this conforms the expectation of neutral selection; (3) In exon4 and exon3, not only was the substitution proportion extremely low, but also PS was much higher than PN (the ratio PS over PN is 19.5 in alleles at IaAa of mouse and 4 among alleles at different loci), this coincides obviously with purification selection. The analysis of GC content of MHC DQA showed that its peaks were in the regions corresponding to the middle bulks of some domains, that the highest and constant level was in exon4 and that GC content in the third codon position (GC III content) associates inversely with PS. These results indicate that the specified maintenance mechanisms of interallelic diversity relevant to their functions exist in given exons corresponding to some domains of the same MHC DQA locus and GC III content is an important factor in keeping the structure and function of gene under selection constraint. The method for estimating nucleotide substitution proportion was modified.

Alleles↗