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L Duret

Publications and source records attributed to L Duret.

14 recordsLinked to original sources

Evolutionary affinities of the order Perissodactyla and the phylogenetic status of the superordinal taxa Ungulata and Altungulata.

Contrary to morphological claims, molecular data indicate that the order Perissodactyla (e.g., horses, rhinoceroses, and tapirs) is neither part of the superordinal taxon Paenungulata (Sirenia, Proboscidea, and Hyracoidea) nor an immediate outgroup of the paenungulates. Rather, Perissodactyla is closer to Carnivora and Cetartiodactyla (Cetacea+Artiodactyla) than it is to the paenungulates. Therefore, two morphologically defined superordinal taxa, Altungulata (Proboscidea, Sirenia, Hyracoidea, and Perissodactyla) and Ungulata (Altungulata and Cetartiodactyla), are invalidated. Perissodactyla, Carnivora, and Cetartiodactyla are shown to constitute a rather tight trichotomy. However, a molecular analysis of 36 protein sequences with a total concatenated length of 7885 aligned amino acids indicates that Perissodactyla is closer to Cetartiodactyla than either taxa is to Carnivora. The relationships among Paenungulata, Primates, and the clade consisting of Perissodactyla, Carnivora, and Cetartiodactylaa could not be resolved on the basis of the available data.

Amino Acid Sequence

Cloning and characterization of a gene encoding a novel immunodominant antigen of Trypanosoma cruzi.

A Trypanosoma cruzi genomic expression library was screened with a pool of sera obtained from chronic chagasic patients. The recombinant antigen (Tc40) isolated from this library reacted with a large number of serum samples of chronic chagasic patients, suggesting that the presence of anti-Tc40 antibodies may be specifically associated to Chagas' disease. The full-length sequence of the Tc40 gene was determined after isolation of genomic and cDNA clones. The Tc40 cDNA includes a large open reading frame (2745 bp-long) that encodes a polypeptide of 100 kDa without any homology with previously described T. cruzi sequences. In contrast with other T. cruzi antigens whose immunodominant B-cell epitopes are composed by amino acid repetitive motifs, Tc40 does not show any amino acid repetition. Antibodies against the Tc40 recombinant protein reacted with three native polypeptides of 100, 41 and 38 kDa which are tightly associated with membranes or cytoskeleton and expressed in all developmental stages of the parasite life cycle. A transcript of 3.9-kb was detected in Northern blot analysis which is large enough to encode a 100 kDa polypeptide. Tc40 genes were mapped on a chromosomal band of 1.1 Mbp and in a few copies per haploid genome in the G strain.

Amino Acid Sequence

Searching for regulatory elements in human noncoding sequences.

Important progress has been made in the past two years in the identification of Pol II promoters. For most other regulatory elements, however, current biological knowledge is still insufficient to allow the development of prediction tools. The phylogenetic-footprinting strategy, which is based on the comparative analysis of homologous sequences, is a very efficient approach to identify new unknown regulatory elements. The recent organization of large-scale sequencing projects for some model vertebrate organisms will be extremely valuable for the prediction of regulatory elements in the human genome.

Animals

Cloning of the mouse BTG3 gene and definition of a new gene family (the BTG family) involved in the negative control of the cell cycle.

It is well known that loss of tumor suppressor genes and more generally of antiproliferative genes plays a key role in the development of most tumors. We report here the cloning of the mouse BTG3 gene and show that its human counterpart maps on chromosome 21. This evolutionarily conserved gene codes for a 30 kDa protein and is expressed in most adult murine and human tissues analyzed. However, we demonstrate that its expression is cell cycle dependent and peaks at the end of the G1 phase. This gene is homologous to the human BTG1, BTG2 and TOB genes which were demonstrated to act as inhibitors of cell proliferation. Its description allowed us to define better this seven gene family (the BTG gene family) at the structural level and to speculate about its physiological role in normal and tumoral cells. This family is mainly characterized by the presence of two conserved domains (BTG boxes A and B) of as yet undetermined function which are separated by a non-conserved 20-25 amino acid sequence.

Amino Acid Sequence

Phylogenetic position of the order Lagomorpha (rabbits, hares and allies)

Ever since they have been classified as ruminants in the Old Testament (Leviticus 11:6, Deuteronomy 14:7) and equated with hyraxes in the vulgate Latin translation, rabbits and their relatives (order Lagomorpha) have frequently experienced radical changes in taxonomic rank. By using 91 orthologous protein sequences, we have attempted to answer the classical question "What, if anything, is a rabbit?". Here we show that Lagomorpha is significantly more closely related to Primates and Scandentia (tree shrews) than it is to rodents. This newly determined phylogenetic position invalidates the superordinal taxon Glires (Lagomorpha + Rodentia), and indicates that the morphological 'synapomorphies' previously used to cluster rodents and lagomorphs into Glires, may actually represent symplesiomorphies or homoplasies that are of no phylogenetic value. This raises the possibility that the ancestral eutherian morphotype may have possessed many rodent-like morphological characters.

Animals

LALNVIEW: a graphical viewer for pairwise sequence alignments.

LALNVIEW is a graphical program for visualising local alignments between two sequences (protein or nucleic acids). Sequences are represented by coloured rectangles to give an overall picture of their similarities. LALNVIEW can display sequence features (exon, intron, active site, domain, propeptide, etc.) along with the alignment. When using LALNVIEW through our Web servers, sequence features are automatically extracted from database annotations (SWISS-PROT, GenBank, EMBL or HOVERGEN) and displayed with the alignment. LALNVIEW is a useful tool for analysing pairwise sequence alignments and for making the link between sequence homology and what is known about the structure or function of sequences. LALNVIEW executables for UNIX, Macintosh and PC computers are freely available from our server (http:// expasy.hcuge.ch/sprot/lalnview.html).

Acyltransferases

Isolation and characterization of a cDNA encoding a chicken actin-like protein.

We report the isolation and characterization of a chicken cDNA which putatively encodes an actin-like protein (chACTL). This 394-amino-acid (aa) polypeptide shares sequence homology (81, 70 and 67% identical aa, respectively) with three actin-related proteins (ARP) described for Drosophila melanogaster (ARP14D), Caenorhabditis elegans (ACTL) and Saccharomyces cerevisiae (ACT2). At least six chACTL transcripts were detected in different tissues during chick embryogenesis. Sequence analysis suggests that at least three groups of ARP have been evolutionarily conserved.

Actins

Statistical analysis of vertebrate sequences reveals that long genes are scarce in GC-rich isochores.

We compared the exon/intron organization of vertebrate genes belonging to different isochore classes, as predicted by their GC content at third codon position. Two main features have emerged from the analysis of sequences published in GenBank: (1) genes coding for long proteins (i.e., > or = 500 aa) are almost two times more frequent in GC-poor than in GC-rich isochores; (2) intervening sequences (= sum of introns) are on average three times longer in GC-poor than in GC-rich isochores. These patterns are observed among human, mouse, rat, cow, and even chicken genes and are therefore likely to be common to all warm-blooded vertebrates. Analysis of Xenopus sequences suggests that the same patterns exist in cold-blooded vertebrates. It could be argued that such results do not reflect the reality because sequence databases are not representative of entire genomes. However, analysis of biases in GenBank revealed that the observed discrepancies between GC-rich and GC-poor isochores are not artifactual, and are probably largely underestimated. We investigated the distribution of microsatellites and interspersed repeats in introns of human and mouse genes from different isochores. This analysis confirmed previous studies showing that L1 repeats are almost absent from GC-rich isochores. Microsatellites and SINES (Alu, B1, B2) are found at roughly equal frequencies in introns from all isochore classes. Globally, the presence of repeated sequences does not account for the increased intron length in GC-poor isochores. The relationships between gene structure and global genome organization and evolution are discussed.

Animals

HOVERGEN: a database of homologous vertebrate genes.

Comparison of homologous genes is a major step for many studies related to genome structure, function or evolution. Similarity search programs easily find genes homologous to a given sequence. However, only very tedious manual procedures allow the retrieval of all sets of homologous genes sequenced for a given set of species. Moreover, this search often generates errors due to the complexity of data to be managed simultaneously: phylogenetic trees, alignments, taxonomy, sequences and related information. HOVERGEN helps to solve these problems by integrating all this information. HOVERGEN corresponds to GenBank sequences from all vertebrate species, with some data corrected, clarified, or completed, notably to address the problem of redundancy. Coding sequences have been classified in gene families. Protein multiple alignments and phylogenetic trees have been calculated for each family. Sequences and related information have been structured in an ACNUC database which permits complex selections. A graphical interface has been developed to visualize and edit trees. Genes are displayed in color, according to their taxonomy. Users have directly access to all information attached to sequences and to multiple alignments simply by clicking on genes. This graphical tool gives thus a rapid and simple access to all data necessary to interpret homology relationships between genes. HOVERGEN allows the user to easily select sets of homologous vertebrate genes, and thus is particularly useful for comparative sequence analysis, or molecular evolution studies.

Animals

Rearrangement of CCND1 (BCL1/PRAD1) 3' untranslated region in mantle-cell lymphomas and t(11q13)-associated leukemias.

Rearrangement and overexpression of CCND1 (BCL1/PRAD1), a member of the cyclin G1 gene family, are consistent features of t(11q13)-bearing B-lymphoid tumors (particularly mantle-cell lymphoma [MCL]). Its deregulation is thought to perturb the G1-S transition of the cell cycle and thereby to contribute to tumor development. As suggested by previously published studies, rearrangement of the 3' untranslated region (3' UTR) of CCND1 may contribute to its activation in some lymphoid tumors. To define further the prevalence of such rearrangements, we report here the result of the molecular study of 34 MCL and six t(11q13)-associated leukemias using a set of probes specific to the different parts of the CCND1 transcript. We also sequenced the entire cDNA of the overexpressed CCND1 transcripts in a t(11q13)-associated leukemia. DNA from four of these 40 patients showed rearrangement of the 3' UTR of CCND1 coexisting with major translocation cluster (MTC) rearrangement. Southern blot and sequence analyses showed that, as a result of these rearrangements, the 3' AU-rich region containing sequences involved in mRNA stability and in translational control is eliminated. Moreover, the finding that the CCND1 mRNA half-life was greater than 3 hours (normal tissues, 0.5 hours) in three t(11q13)-associated cell lines stresses the importance of posttranscriptional derangement in the activation of CCND1. Finally, we did not observe any mutation in the coding frame of the CCND1 cDNA analyzed.

Amino Acid Sequence

Sequence analysis reveals that the BTG1 anti-proliferative gene is conserved throughout evolution in its coding and 3' non-coding regions.

The human BTG1 gene (expressing an anti-proliferative function) is an evolutionarily conserved gene homologous to the murine PC3/TIS21 genes. Here, we report the cloning and sequencing of the murine BTG1 coding region and chicken BTG1 cDNA. The putative human and mouse BTG1 proteins are 100% identical; the chicken BTG1 cDNA contains an open reading frame of 170 amino acids with a 91% identity to its human and murine counterparts. The 3'-untranslated region of BTG1 is also highly conserved (82% homology between human and chicken), suggesting that it plays a key role in the regulation of BTG1 expression. These data confirm that BTG1 is phylogenetically highly conserved and that BTG1 and PC3/TIS21 may constitute the first members of a new family of functionally related genes.

Amino Acid Sequence

Strong conservation of non-coding sequences during vertebrates evolution: potential involvement in post-transcriptional regulation of gene expression.

Comparison of nucleotide sequences from different classes of vertebrates that diverged more than 300 million years ago, revealed the existence of highly conserved regions (HCRs) with more than 70% similarity over 100 to 1450 nt in non-coding parts of genes. Such a conservation is unexpected because it is much longer and stronger than what is necessary for specifying the binding of a regulatory protein. HCRs are relatively frequent, particularly in genes that are essential to cell life. In multigene families, conserved regions are specific of each isotype and are probably involved in the control of their specific pattern of expression. Studying HCRs distribution within genes showed that functional constraints are generally much stronger in 3'-non-coding regions than in promoters or introns. The 3'-HCRs are particularly A + T-rich and are always located in the transcribed untranslated regions of genes, which suggests that they are involved in post-transcriptional processes. However, current knowledge of mechanisms that regulate mRNA export, localisation, translation, or degradation is not sufficient to explain the strong functional constraints that we have characterised.

Animals

BTG1, a member of a new family of antiproliferative genes.

The BTG1 gene locus has been shown to be involved in a t(8;12)(q24;q22) chromosomal translocation in a case of B-cell chronic lymphocytic leukemia. We report here the cloning and sequencing of the human BTG1 cDNA and establish the genomic organization of this gene. The full-length cDNA isolated from a lymphoblastoid cell line contains an open reading frame of 171 amino acids. BTG1 expression is maximal in the G0/G1 phases of the cell cycle and is down-regulated when cells progress throughout G1. Furthermore, transfection experiments of NIH3T3 cells indicate that BTG1 negatively regulates cell proliferation. The BTG1 open reading frame is 60% homologous to PC3, an immediate early gene induced by nerve growth factor in rat PC12 cells. Sequence and Northern blot analyses indicate that BTG1 and PC3 are not cognate genes. We then postulate that these two genes are the first members of a new family of antiproliferative genes.

3T3 Cells