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At least 199 records · Page 11Linked to original sources
PubMed1995

The class II aminoacyl-tRNA synthetases and their active site: evolutionary conservation of an ATP binding site.

Previous sequence analyses have suggested the existence of two distinct classes of aminoacyl-tRNA synthetase. The partition was established on the basis of exclusive sets of sequence motifs (Eriani et al. [1990] Nature 347:203-306). X-ray studies have now well defined the structural basis of the two classes: the class I enzymes share with dehydrogenases and kinases the classic nucleotide binding fold called the Rossmann fold, whereas the class II enzymes possess a different fold, not found elsewhere, built around a six-stranded antiparallel beta-sheet. The two classes of synthetases catalyze the same global reaction that is the attachment of an amino acid to the tRNA, but differ as to where on the terminal adenosine of the tRNA the amino acid is placed: class I enzymes act on the 2' hydroxyl whereas the class II enzymes prefer the 3' hydroxyl group. The three-dimensional structure of aspartyl-tRNA synthetase from yeast, a typical class II enzyme, is described here, in relation to its function. The crucial role of the sequence motifs in substrate binding and enzyme structure is high-lighted. Overall these results underline the existence of an intimate evolutionary link between the aminoacyl-tRNA synthetases, despite their actual structural diversity.

Adenosine Triphosphate↗
PubMed2005

Evolutionary conservation of expression profiles between human and mouse orthologous genes.

Mouse models are often used to study human genes because it is believed that the expression and function are similar for the majority of orthologous genes between the two species. However, recent comparisons of microarray data from thousands of orthologous human and mouse genes suggested rapid evolution of gene expression profiles under minimal or no selective constraint. These findings appear to contradict non-array-based observations from many individual genes and imply the uselessness of mouse models for studying human genes. Because absolute levels of gene expression are not comparable between species when the data are generated by species-specific microarrays, use of relative mRNA abundance among tissues (RA) is preferred to that of absolute expression signals. We thus reanalyze human and mouse genome-wide gene expression data generated by oligonucleotide microarrays. We show that the mean correlation coefficient among expression profiles detected by different probe sets of the same gene is only 0.38 for humans and 0.28 for mice, indicating that current measures of expression divergence are flawed because the large estimation error (discrepancy in expression signal detected by different probe sets of the same gene) is mistakenly included in the between-species divergence. When this error is subtracted, 84% of human-mouse orthologous gene pairs show significantly lower expression divergence than that of random gene pairs. In contrast to a previous finding, but consistent with the common sense, expression profiles of orthologous tissues between species are more similar to each other than to those of nonorthologous tissues. Furthermore, the evolutionary rate of expression divergence and that of coding sequence divergence are found to be weakly, but significantly positively correlated, when RA and the Euclidean distance are used to measure expression-profile divergence. These results highlight the importance of proper consideration of various estimation errors in comparing the microarray data between species.

Animals↗
PubMed1999

Threading with explicit models for evolutionary conservation of structure and sequence.

We have attempted to predict the three-dimensional structures of 19 proteins for the CASP3 experiment, each showing less than 25% sequence identity with known structures. Predictions were based on a threading method that aligns the target sequence with the conserved cores of structural templates, as identified from structure-structure alignments of the template with homologous neighbors. Alternative alignments were scored using contact potentials and a position-specific score matrix derived from sequence neighbors of the template. We find that this method identified the correct structural family for 11 of the 19 targets and predicted the remaining 8 targets to be similar to "none" of the templates, avoiding false positives. Threading alignments are relatively accurate for 10 of the 11 targets, including alignments for 6 of 7 identified at CASP3 as fold-recognition targets. These predictions were ranked "first place" by the CASP3 assessor when compared to fold-recognition predictions made by other methods. It appears that threading with family-specific models for structure and sequence conservation has improved threading prediction accuracy.

Algorithms↗
PubMed1996

Evolutionary conservation of a genetic pathway of programmed cell death.

Genetic analysis of programmed cell death in Caenorhabditis elegans has led to the identification of 13 genes that constitute a developmental pathway of programmed cell death. Two of the three key genes in this pathway, ced-9, a cell death suppressor, and ced-3, a cell death inducer, were found to encode proteins that share structural and functional similarities with the mammalian proto-oncogene product Bcl-2 and interleukin-1 beta converting enzyme, respectively. These results suggest that the genetic pathway of programmed cell death may be evolutionarily conserved from worms to mammals.

Animals↗
PubMed1998

Mouse Odf2 cDNAs consist of evolutionary conserved as well as highly variable sequences and encode outer dense fiber proteins of the sperm tail.

The outer dense fibers (ODF) of the mammalian sperm tail comprise a unique, specialized, and very prominent structure, consisting of nine fibers surrounding the axoneme. The ODF may play an important but as yet undefined role in sperm morphology, integrity and function. Study of the ODF is hampered by insufficient knowledge of their protein composition and the genetic regulation of their synthesis. We report here on the characterization of cDNAs encoding the Odf2 proteins of outer dense fibers of mouse sperm. We isolated two cDNA clones with variable 5' regions. Variability in sequence is restricted to specific regions in the N-terminal part of the encoded proteins, whereas the C-terminal part is highly conserved in Odf2 proteins both between species and within a species. This variability is confirmed at the protein level. The outer dense fibers could be detected immunologically in total sperm tails allowing a direct comparison of their length in relation to the length of the sperm tail. Odf2 transcripts could be demonstrated in testicular RNA and are restricted to germ cells. The start of transcription is in step 5 spermatids of tubular stage V and the RNA could be detected in the cytoplasm of differentiating spermatids in all subsequent tubular stages.

Amino Acid Sequence↗
PubMed1998

Evolutionary conservation of mechanisms upstream of asymmetric Nodal expression: reconciling chick and Xenopus.

Recent experiments have suggested a pathway of genes that regulate left-right asymmetry in vertebrate embryogenesis. The most downstream member of this cascade is nodal (XNR-1 in frogs), which is expressed in the left-side lateral mesoderm. Previous work in the chick [Levin, 1998] suggests that an inductive interaction by Shh (Sonic hedgehog) present at the midline was needed for the left-sided expression of nodal, which by default would not be expressed. Interestingly, it has been reported [Lohr et al., 1997] that in Xenopus, right-side mesoderm that is explanted at st. 15 and allowed to develop in culture, goes on to express nodal, suggesting that lateral mesoderm expresses this gene by default and that a repression of nodal by the midline is needed to achieve asymmetry. Such a contradiction raises interesting questions about the degree of conservation of the mechanisms upstream of nodal asymmetry and, in general, about the differences in the LR pathway among species. Thus we examined this issue directly. We show that in the chick, as in the frog, explanted mesoderm from both sides does, indeed, go on to express nodal, including both the medial and lateral expression domains. Ectopic nodal expression in the medial domain on the right side is not sufficient to induce an ectopic lateral domain. We also show that explanted lateral tissue regenerates node/notochord structures exhibiting Shh expression. Furthermore, we show that Xenopus explants done at st. 15 also regenerate notochord by the stage at which XNR-1 would be expressed. Thus explants are not isolated from the influence of the midline. In contrast to the midline repressor model previously suggested [Lohr et al., 1997] to explain the presence of nodal expression in explants, we propose that the expression is due to induction by signals secreted by regenerating node and notochord tissue (Shh in the chick). Thus our results are consistent with Shh being necessary for nodal induction in both species, and we provide an explanation for both sets of data in terms of a single conserved mechanism upstream of nodal expression.

Animals↗
PubMed2005

Evolutionary conservation of the egr-1 immediate-early gene response in a teleost.

Immediate-early gene expression is a key part of a neuron's response to behaviorally relevant stimuli and, as a result, localization of immediate-early gene expression can be a useful marker for neural activity. We characterized the immediate-early gene egr-1 (also called zif268, NGFI-A, krox-24, ZENK) in the teleost Astatotilapia (Haplochromis) burtoni. We compared the A. burtoni egr-1 predicted protein sequence to that of other vertebrates, characterized its gene expression time course, and localized its induced expression throughout the brain. The A. burtoni egr-1 predicted protein shared putative functional domains with egr-1 of other vertebrates and shared 81% sequence similarity with zebrafish and 66% with mouse. We identified distinct mammalian and teleost inserts rich in serine residues within one activation domain, suggesting convergent responses to selection pressures to increase the number of serine residues in this region. Functionally, we found that A. burtoni egr-1 gene expression peaked near 30 minutes after pharmacological stimulation and thereby displayed the transient expression above basal levels characteristic of egr-1 expression in birds and mammals. Finally, we observed distinct patterns of egr-1 gene induction in the brain by natural and pharmacological stimuli. Unstimulated males had very low expression levels of egr-1, whereas males stimulated by their normal environment showed higher levels of expression specific to particular brain regions. Males injected with a glutamate receptor agonist also had region-specific induction of egr-1 expression. We conclude that the egr-1 immediate-early gene response is evolutionarily conserved and will, therefore, be useful for identifying functional neural responses in nontraditional model species.

Animals↗
PubMed2005

Zebrafish id2 developmental expression pattern contains evolutionary conserved and species-specific characteristics.

The inhibitor of differentiation or inhibitor of DNA binding (Id) family are members of the helix-loop-helix (HLH) group of transcription factors that play important roles in cell proliferation, differentiation, cell cycle control, and apoptosis. They modulate the formation of active class A-class B basic HLH (bHLH) complexes. Ids lack the amino-terminal associated basic region necessary for DNA binding, thus sequestering the class A factors, inhibiting the formation of active class A-class B heterodimers and, therefore, are considered to act as dominant-negative regulators of differentiation pathways. We isolated zebrafish id2, and its expression during development was characterized. id2, in addition to regions of expression detected in Xenopus and mice, is also expressed in the tegmentum; midbrain-hindbrain boundary; cerebellum; rhombomeres 2,3,4,6; notochord; and corpuscles of Stannius. Furthermore, we show that expression of id2 is repressed in mind bomb mutants, suggesting a role of Notch upstream of Id2.

Amino Acid Sequence↗
PubMed2001

PaHB1 is an evolutionary conserved HD-GL2 homeobox gene expressed in the protoderm during Norway spruce embryo development.

In angiosperms, the protoderm or outer cell layer is the first tissue to differentiate in the embryo proper. In gymnosperms, it is not known whether a protoderm is defined and similarly differentiated. Here, we report a cDNA designated PaHB1 (for Picea abies Homeobox1), which is expressed during somatic embryogenesis in Norway spruce. PaHB1 exon/intron organization and its corresponding protein are highly similar to those of the HD-GL2 angiosperm counterparts. A phylogenetic analysis reveals that PaHB1 is strongly associated with one subclass consisting of protoderm/epiderm-specific genes. Moreover, PaHB1 expression switches from a ubiquitous expression in proembryogenic masses to an outer cell layer-specific localization during somatic embryo development. Ectopic expression of PaHB1 in somatic embryos leads to an early developmental block. The transformed embryos lack a smooth surface. These findings show that the PaHB1 expression pattern is highly analogous to angiosperm HD-GL2 homologues, suggesting similarities in the definition of the outer cell layer in seed plants.

Amino Acid Sequence↗
PubMed1985

Yeast ribosomal protein L25 binds to an evolutionary conserved site on yeast 26S and E. coli 23S rRNA.

The binding site of the yeast 60S ribosomal subunit protein L25 on 26S rRNA was determined by RNase protection experiments. The fragments protected by L25 originate from a distinct substructure within domain IV of the rRNA, encompassing nucleotides 1465-1632 and 1811-1861. The protected fragments are able to rebind to L25 showing that they constitute the complete protein binding site. This binding site is remarkably conserved in all 23/26/28S rRNAs sequenced to date including Escherichia coli 23S rRNA. In fact heterologous complexes between L25 and E. coli 23S rRNA could be formed and RNase protection studies on these complexes demonstrated that L25 indeed recognizes the conserved structure. Strikingly the L25 binding site on 23S rRNA is virtually identical to the previously identified binding site of E. coli ribosomal protein EL23. Therefore EL23 is likely to be the prokaryotic counterpart of L25 in spite of the limited homology displayed by the amino acid sequences of the two proteins.

Amino Acid Sequence↗
PubMed1985

The nucleotide sequence of the human int-1 mammary oncogene; evolutionary conservation of coding and non-coding sequences.

The mouse mammary tumor virus can induce mammary tumors in mice by proviral activation of an evolutionarily conserved cellular oncogene called int-1. Here we present the nucleotide sequence of the human homologue of int-1, and compare it with the mouse gene. Like the mouse gene, the human homologue contains a reading frame of 370 amino acids, with only four substitutions. The amino acid changes are all in the hydrophobic leader domain of the int-1 encoded protein, and do not significantly alter its hydropathic index. The conservation between the mouse and the human int-1 genes is not restricted to exons; extensive parts of the introns are also homologous. Thus, int-1 ranks among the most conserved genes known, a property shared with other oncogenes.

Amino Acid Sequence↗
PubMed1985

The 5' region of the p53 gene: evolutionary conservation and evidence for a negative regulatory element.

The 5' regions of the mouse, rat and human functional p53 genes were isolated and analysed. All three genes possess a non-coding exon, comprising exclusively 5' untranslated sequences. This exon contains extensive diad symmetry near the 5' end of p53 mRNA, possibly allowing for the formation of a stable hairpin structure in this mRNA. The nucleotide sequence within this hairpin element is highly conserved among the species. A DNA stretch of 225 bp preceding the p53 mRNA cap site possesses distinct promoter activity when assayed in the CAT system. However, this activity is practically abolished when further upstream p53 sequences (approximately 120 bp) are included in front of the CAT gene. This suggests that the control of p53 gene expression is complex and involves a negative regulatory element.

Animals↗
PubMed1986

Evolutionary conserved close linkage of the c-fes/fps proto-oncogene and genetic sequences encoding a receptor-like protein.

Recently we described that genetic sequences in the immediately upstream region of the c-fes/fps proto-oncogene, designated fur, constituted a transcription unit for a 4.5-kb mRNA. Here we present characteristics of the genetic organization of fur and some features of its putative translation product which we call furin. The nucleotide sequence of a 3.1-kbp fur-specific cDNA isolated from a human cDNA library revealed an open reading frame of 1,498 bp from which the 499 carboxy-terminal amino acids of the primary fur translational product could be deduced. Computer analysis indicated that furin contained a possible transmembrane domain which resembled that of class II MHC antigens. Furthermore, a cysteine-rich region was present. Significant homology, especially with respect to the topography of cysteine residues, was found between the cysteine-rich regions of the human insulin receptor, the human epidermal growth factor receptor and furin. From the data presented here we deduce that fur may encode a membrane-associated protein with a recognition function.

Amino Acid Sequence↗
PubMed1987

A new mouse TCR V gamma gene that shows remarkable evolutionary conservation.

We have identified a new mouse T-cell receptor V gamma gene segment, V gamma 4.4, which frequently undergoes rearrangements in AKR thymomas, and at a lower frequency in fetal thymocytes. V gamma 4.4 is the fourth and the most 5' V gene segment in the gamma 4 cluster, being 7.3 kb from V gamma 4.3. Surprisingly, V gamma 4.4 is more homologous to eight human V gamma genes than to the other mouse V gamma genes. It has only a 38% nucleotide and 21% amino acid sequence homology to the most homologous mouse V gamma gene (V gamma 4.1), whereas these homologies to the human V gamma 8 gene are as high as 68% and 48% respectively.

Animals↗
PubMed1987

Differentially expressed bovine cytokeratin genes. Analysis of gene linkage and evolutionary conservation of 5'-upstream sequences.

Cytokeratins are a family of approximately 20 polypeptides which form the intermediate-sized filaments (IFs) characteristic of epithelial cells. They are synthesized co-ordinately as 'pairs' consisting of one representative from each of the two cytokeratin subfamilies, i.e. the acidic (type I) and the more basic (type II) polypeptides, in cell type-specific combinations. We have isolated and characterized the genes coding for four bovine cytokeratins of the basic (type II) subfamily, i.e. cytokeratins Ib, III, IV and 6*, by Southern blot hybridization, hybridization-selection-translation experiments, hetero-duplex mapping, and partial sequencing of the exons coding for the hypervariable carboxy-terminal 'tail' regions of the proteins and the 3'-non-translated ends of the mRNAs which are distinct for the individual cytokeratin polypeptides. Limited 'chromosomal walk' experiments demonstrated that the genes are organized into two tandems, i.e. 6*----Ib and III----IV, in which they are separated by approximately 11 kb. RNA analysis by Northern and dot blots show that both genes of the III----IV tandem are co-expressed in some bovine tissues (muzzle epidermis, hoof pad and tongue mucosa) and cultured cells (BMGE + H) but that in other tissues, cornea for example, only the gene encoding III is expressed. Unexpectedly, the genes linked in the tandem 6*----Ib are not co-expressed in any of the tissues examined. mRNA from gene 6* has been found in tongue mucosa but in none of the other cell lines and tissues examined, whereas mRNA for cytokeratin Ib is expressed in cornea and muzzle epidermis but not in, for example, tongue mucosa and in the epidermis of the heel pad.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2005

Characterization of five evolutionary conserved regions of the human tyrosine hydroxylase (TH) promoter: implications for the engineering of a human TH minimal promoter assembled in a self-inactivating lentiviral vector system.

A DNA fragment of about 13 kb containing the human tyrosine hydroxylase (TH) promoter was previously isolated from a genomic DNA library and sequenced. The 11 kb from the transcription start of the human TH promoter was successively joined to the green fluorescent protein (GFP) to generate a transgenic mouse model. High levels of GFP expression could be observed in TH-positive cells of the Substantia nigra of embryonic and adult mice. Intriguingly, the sequence of the human TH promoter showed a low degree of homology with the mouse and rat TH promoters. In fact, comparative analysis of the sequences of human, rat, and mouse TH promoters revealed only five small regions of high homology. These five evolutionarily conserved regions were numbered in numeric progression from the 5' end of human TH promoter. In the present study, a panel of minimal human TH promoters was generated to analyze the transcriptional activity and specificity of gene expression conferred by the five conserved regions (CRs). The series of constructs was termed 250 bp and contained the first -194 bp of the human TH promoter immediately upstream of the transcription start, the first 35 bp the human TH messenger RNA leader, plus one or more of the five CRs. All the constructs were assembled in a self-inactivating form of the latest series of lentiviral vector system based on the human immunodeficiency virus type 1 (HIV-1). Lentiviral-mediated gene transfer was highly efficient for the in vitro transduction of human neuronal progenitor cells (hNPCs). Since a subset of hNPCs express TH following in vitro treatment with a mixture of differentiating agents, it was possible to assess specificity of expression for all the minimal human TH promoters. Overall, the successive addition of the five conserved regions produced a greater degree of specificity in induced TH-positive hNPCs, in particular after the addition of CRI (-8,917, -8,876). However, the human TH minimal promoters did not show any specificity for TH-positive differentiated mouse primary striatal and S. nigra cells, indicating a difference of TH gene regulation between the human and mouse systems. The human TH minimal promoters may provide the opportunity for the selection of TH-positive human embryonic and adult stem cells for brain transplantation experiments in animal models for Parkinson's disease.

Animals↗
PubMed2001

Testing the vulnerability of the phylotypic stage: on modularity and evolutionary conservation.

The phylotypic stage is the developmental stage at which vertebrates most resemble each other. In this study we test the plausibility of the hypotheses of Sander [1983, Development and Evolution, Cambridge University Press] and Raff [1994, Early Life on Earth, Columbia University Press; 1996, The Shape of Life, University of Chicago Press] that the phylotypic stage is conserved due to the intense and global interactivity occurring during that stage. First, we test the prediction that the phylotypic stage is much more vulnerable than any other stage. A search of the teratological literature shows that disturbances at this stage lead to a much higher mortality than in other stages, in accordance with the prediction. Second, we test whether that vulnerability is indeed caused by the interactiveness and lack of modularity of the inductions or, alternatively, is caused by some particularly vulnerable process going on at that time. From the pattern of multiple induced anomalies we conclude that it is indeed the interactiveness that is the root cause of the vulnerability. Together these results support the hypotheses of Sander and Raff. We end by presenting an argument on why the absence of modularity in the inductive interactions may also be the root cause of the conservation of the much discussed temporal and spatial colinearity of the Hox genes. J. Exp. Zool. (Mol. Dev. Evol.) 291:195-204, 2001.

Animals↗
PubMed2004

Phospholipid hydroperoxide glutathione peroxidase: expression pattern during testicular development in mouse and evolutionary conservation in spermatozoa.

Phospholipid hydroperoxide glutathione peroxidase (PHGPx) is a selenoprotein belonging to the family of glutathione peroxidases and has been implicated in antioxidative defense and spermatogenesis. PHGPx accounts for almost the entire selenium content of mammalian testis. In an attempt to verify the expression pattern of PHGPx, testes of mouse mutants with arrest at different stages of germ cell development and testes of mice at different ages were subjected to immunostaining with a monoclonal anti-PHGPx antibody. PHGPx was detected in Leydig cells of testes in all developmental stages. In the seminiferous tubuli, the PHGPx staining was first observed in testes of 21-day-old mice which is correlated with the appearance of the first spermatids. This result was confirmed when the testes of mutant mice with defined arrest of germ cell development were used. An immunostaining was observed in the seminiferous tubuli of olt/olt and qk/qk mice which show an arrest at spermatid differentiation. In Western blot analysis of proteins extracted from testes of mutant mice and from developing testes, two signals at 19- and 22-kDa were observed which confirm the existence of two PHGPx forms in testicular cells. In mouse spermatozoa, a subcellular localization of PHGPx and sperm mitochondria-associated cysteine-rich protein (SMCP) was demonstrated, indicating the localization of PHGPx in mitochondria of spermatozoa midpiece. For verifying the midpiece localization of PHGPx in other species, spermatozoa of Drosophila melanogaster, frog, fish, cock, mouse, rat, pig, bull, and human were used in immunostaining using anti-PHGPx antibody. A localization of PHGPx was found in the midpiece of spermatozoa in all species examined. In electronmicroscopical analysis, PHGPx signals were found in the mitochondria of midpiece. These results indicate a conserved crucial role of PHGPx during sperm function and male fertility.

Animals↗