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At least 685 records · Page 38Linked to original sources
PubMed2003

The WD-repeat protein superfamily in Arabidopsis: conservation and divergence in structure and function.

BACKGROUND: The WD motif (also known as the Trp-Asp or WD40 motif) is found in a multitude of eukaryotic proteins involved in a variety of cellular processes. Where studied, repeated WD motifs act as a site for protein-protein interaction, and proteins containing WD repeats (WDRs) are known to serve as platforms for the assembly of protein complexes or mediators of transient interplay among other proteins. In the model plant Arabidopsis thaliana, members of this superfamily are increasingly being recognized as key regulators of plant-specific developmental events. RESULTS: We analyzed the predicted complement of WDR proteins from Arabidopsis, and compared this to those from budding yeast, fruit fly and human to illustrate both conservation and divergence in structure and function. This analysis identified 237 potential Arabidopsis proteins containing four or more recognizable copies of the motif. These were classified into 143 distinct families, 49 of which contained more than one Arabidopsis member. Approximately 113 of these families or individual proteins showed clear homology with WDR proteins from the other eukaryotes analyzed. Where conservation was found, it often extended across all of these organisms, suggesting that many of these proteins are linked to basic cellular mechanisms. The functional characterization of conserved WDR proteins in Arabidopsis reveals that these proteins help adapt basic mechanisms for plant-specific processes. CONCLUSIONS: Our results show that most Arabidopsis WDR proteins are strongly conserved across eukaryotes, including those that have been found to play key roles in plant-specific processes, with diversity in function conferred at least in part by divergence in upstream signaling pathways, downstream regulatory targets and /or structure outside of the WDR regions.

Animals↗
PubMed2006

FtsZ from divergent foreign bacteria can function for cell division in Escherichia coli.

FtsZs from Mycoplasma pulmonis (MpuFtsZ) and Bacillus subtilis (BsFtsZ) are only 46% and 53% identical in amino acid sequence to FtsZ from Escherichia coli (EcFtsZ). In the present study we show that MpuFtsZ and BsFtsZ can function for cell division in E. coli provided we make two modifications. First, we replaced their C-terminal tails with that from E. coli, giving the foreign FtsZ the binding site for E. coli FtsA and ZipA. Second, we selected for mutations in the E. coli genome that facilitated division by the foreign FtsZs. These suppressor strains arose at a relatively high frequency of 10(-3) to 10(-5), suggesting that they involve loss-of-function mutations in multigene pathways. These pathways may be negative regulators of FtsZ or structural pathways that facilitate division by slightly defective FtsZ. Related suppressor strains were obtained for EcFtsZ containing certain point mutations or insertions of yellow fluorescent protein. The ability of highly divergent FtsZs to function for division in E. coli is consistent with a two-part mechanism. FtsZ assembles the Z ring, and perhaps generates the constriction force, through self interactions; the downstream division proteins remodel the peptidoglycan wall by interacting with each other and the wall. The C-terminal peptide of FtsZ, which binds FtsA, provides the link between FtsZ assembly and peptidoglycan remodeling.

Bacillus subtilis↗
PubMed2005

Pervasive adaptive evolution in primate seminal proteins.

Seminal fluid proteins show striking effects on reproduction, involving manipulation of female behavior and physiology, mechanisms of sperm competition, and pathogen defense. Strong adaptive pressures are expected for such manifestations of sexual selection and host defense, but the extent of positive selection in seminal fluid proteins from divergent taxa is unknown. We identified adaptive evolution in primate seminal proteins using genomic resources in a tissue-specific study. We found extensive signatures of positive selection when comparing 161 human seminal fluid proteins and 2,858 prostate-expressed genes to those in chimpanzee. Seven of eight outstanding genes yielded statistically significant evidence of positive selection when analyzed in divergent primates. Functional clues were gained through divergent analysis, including several cases of species-specific loss of function in copulatory plug genes, and statistically significant spatial clustering of positively selected sites near the active site of kallikrein 2. This study reveals previously unidentified positive selection in seven primate seminal proteins, and when considered with findings in Drosophila, indicates that extensive positive selection is found in seminal fluid across divergent taxonomic groups.

Animals↗
PubMed2000

Convenient iterative synthesis of an octameric tetracarboxylate-functionalized oligophenylene rod with divergent end groups

Oligo(p-phenylene) rigid rod 10 is synthesized via a functional group-tolerant molecular doubling approach. Preparative chromatographic methods, protecting groups, boronic acid isolations, and Grignard or organolithium reagents are not used. The convenient synthesis of well-defined, polar-functionalized oligophenylene rigid rods could afford ready access to a variety of useful electronic organic materials.

Journal Article↗
PubMed1987

Sequence and functional analysis of a divergent promoter from a cryptic plasmid of Lactobacillus acidophilus 168 S.

We have characterized three of at least five plasmids borne by Lactobacillus acidophilus 168 S. Restriction mapping indicates extensive sequence homology between at least two of them (p1 and p3). We have cloned them in Escherichia coli, and for the smallest (p1) we present the sequence of a region with two divergently arranged promoters which probably share a symmetrical (TTTAAA)-35 box and function efficiently in E. coli cells; an open reading frame contiguous to the promoter, which codes for a 120 amino acid protein of unknown function, and is transcribed in E. coli; and a transcription termination sequence next to this open reading frame. The promoter region contains an AT cluster which is similar to that of the ori2 region of the E. coli F plasmid, and is probably involved in the control of the replication of p1.

Base Sequence↗
PubMed2004

The functional genomic distribution of protein divergence in two animal phyla: coevolution, genomic conflict, and constraint.

We compare the functional spectrum of protein evolution in two separate animal lineages with respect to two hypotheses: (1) rates of divergence are distributed similarly among functional classes within both lineages, indicating that selective pressure on the proteome is largely independent of organismic-level biological requirements; and (2) rates of divergence are distributed differently among functional classes within each lineage, indicating species-specific selective regimes impact genome-wide substitutional patterns. Integrating comparative genome sequence with data from tissue-specific expressed-sequence-tag (EST) libraries and detailed database annotations, we find a functional genomic signature of rapid evolution and selective constraint shared between mammalian and nematode lineages despite their extensive morphological and ecological differences and distant common ancestry. In both phyla, we find evidence of accelerated evolution among components of molecular systems involved in coevolutionary change. In mammals, lineage-specific fast evolving genes include those involved in reproduction, immunity, and possibly, maternal-fetal conflict. Likelihood ratio tests provide evidence for positive selection in these rapidly evolving functional categories in mammals. In contrast, slowly evolving genes, in terms of amino acid or insertion/deletion (indel) change, in both phyla are involved in core molecular processes such as transcription, translation, and protein transport. Thus, strong purifying selection appears to act on the same core cellular processes in both mammalian and nematode lineages, whereas positive and/or relaxed selection acts on different biological processes in each lineage.

Amino Acid Substitution↗
PubMedDate not supplied

Hox gene duplication and deployment in the annelid leech Helobdella.

The segmented leeches are members of the phylum Annelida within the Lophotrochozoa. Here, we describe the isolation of a new Hox gene, Lox18, in the leech Helobdella triserialis. Phylogenetic analysis indicates that Lox18 is a Deformed (Dfd) ortholog. H. triserialis has at least two Dfd orthologs, Lox18 and the previously described Lox6 (Kourakis et al. 1997; Wong and Macagno 1998), indicating that these genes duplicated after the last common ancestor of annelids and arthropods. Although the temporal appearance of Lox18 message is similar to that of Lox6, the spatial pattern is different. Lox18 does not have a sharply defined anterior border of expression in the second neuromere of the subesophageal ganglion of the central nervous system (CNS) as does Lox6, but is expressed uniformly in a small subset of cells in the longitudinal connectives and lateral roots in every segment of the CNS along the entire anterior-posterior (AP) axis. Even though Lox18 shares greater sequence similarity within the homeodomain and flanking regions to Drosophila Dfd than to the previously isolated Lox6, its expression pattern suggests that its function has diverged from the ancestral Hox function. Previous sampling has indicated that the last common ancestor of protostomes and deuterostomes had as many as 10 clustered Hox genes representing distinct paralogy groups (Irvine et al. 1997; de Rosa et al. 1999); leech Hox genes may have undergone subsequent and independent cluster or genome-wide duplication. These results point to the need for total genome level understanding for key members of the Lophotrochozoa.

Amino Acid Sequence↗
PubMed1999

Molecular evolution of the opioid/orphanin gene family.

Gene duplication is a recurring theme in the evolution of vertebrate polypeptide hormones and neuropeptides. These duplication events can lead to the formation of gene families in which divergence of function is the usual outcome. In the case of the opioid/orphanin family of genes, duplication events have proceeded along two paths: (a) an apparent duplication of function as seen in the analgesic activity of Proenkephalin and Prodynorphin end-products; and (b) divergence of function as seen in the nociceptic activity of Proorphanin end-products or the melanocortin (color change and chronic stress regulation) activity of Proopiomelanocortin end-products. Although genes coding for Proopiomelanocortin, Proenkephalin, Prodynorphin, and Proorphanin have been extensively studied in mammals, the distribution and radiation of these genes in nonmammalian vertebrates is less well understood. This review will present the hypothesis that the radiation of the opioid/orphanin gene family is the result of the duplication and divergence of the Proenkephalin gene during the radiation of the chordates. To evaluate the Proenkephalin gene duplication hypothesis, a 3'RACE procedure was used to screen for the presence of Prodynorphin-related, Proenkephalin-related, and Proorphanin-related cDNAs expressed in the brains of nonmammalian vertebrates.

Amino Acid Sequence↗
PubMed1999

The Zn-peptidase superfamily: functional convergence after evolutionary divergence.

Zn-dependent carboxypeptidases (ZnCP) cleave off the C-terminal amino acid residues from proteins and peptides. Here we describe a superfamily that unites classical ZnCP with other enzymes, most of which are known (or likely) to participate in metal-dependent peptide bond cleavage, but not necessarily in polypeptide substrates. It is demonstrated that aspartoacylase (ASP gene) and succinylglutamate desuccinylase (ASTE gene) are members of the ZnCP family. The Zn-binding site along with the structural core of the protein is shown to be conserved between ZnCP and another large family of hydrolases that includes mostly aminopeptidases (ZnAP). Both families (ZnCP and ZnAP) include not only proteases but also enzymes that perform N-deacylation, and enzymes that catalyze N-desuccinylation of amino acids. This is a result of functional convergence that apparently occurred after the divergence of the two families.

Amidohydrolases↗
PubMed1999

Expression and function of members of a divergent nuclear receptor family in Caenorhabditis elegans.

Nuclear receptors (NRs) are a large class of ligand-regulated transcriptional modulators that have been shown to play roles in many developmental processes. The Caenorhabditis elegans genome is predicted to encode a large and divergent family of NR proteins. The functions of most of these genes are unknown. As a first step toward defining their roles, we have initiated an expression and functional survey of a subset of these genes. In this study, we demonstrate expression of 21 of 28 NR genes examined, indicating that a large fraction of the predicted genes likely encode functional gene products. We show that five genes are expressed predominantly in neuronal cells, while others are expressed in multiple cell types. Interestingly, we find that eight genes are expressed exclusively in the lateral hypodermal (seam) cells. These eight genes share a high degree of overall homology and cluster in a neighbor-joining tree derived from sequence analysis of the NRs, suggesting that they arose by gene duplication from a common ancestor. We show that overexpression of each of three members of this subfamily results in similar developmental defects, consistent with a redundant role for these genes in the function of the lateral hypodermal cells.

Animals↗
PubMed2004

Noncoding regulatory sequences of Ciona exhibit strong correspondence between evolutionary constraint and functional importance.

We show that sequence comparisons at different levels of resolution can efficiently guide functional analyses of regulatory regions in the ascidians Ciona savignyi and Ciona intestinalis. Sequence alignments of several tissue-specific genes guided discovery of minimal regulatory regions that are active in whole-embryo reporter assays. Using the Troponin I (TnI) locus as a case study, we show that more refined local sequence analyses can then be used to reveal functional substructure within a regulatory region. A high-resolution saturation mutagenesis in conjunction with comparative sequence analyses defined essential sequence elements within the TnI regulatory region. Finally, we found a significant, quantitative relationship between function and sequence divergence of noncoding functional elements. This work demonstrates the power of comparative sequence analysis between the two Ciona species for guiding gene regulatory experiments.

Animals↗
PubMed2002

Heterogeneously functionalized dendrimers.

Significant timely advances have been made in the synthesis of heterogeneously functionalized dendrimers. Convergent, divergent and other functionalization techniques have been used to create a variety of complex dendrimer motifs with more than one type of surface group. Synthetic advances, as well as pertinent applications of heterogeneously functionalized dendrimers, are reviewed.

Animals↗
PubMed2003

The niobaziridine-hydride functional group: synthesis and divergent reactivity.

A multistep synthetic strategy enables the isolation of the niobaziridine-hydride complex Nb(H)(eta2-tBu(H)C=NAr)(N[Np]Ar)2 (1, Np = neopentyl, Ar = 3,5-C6H3Me2), which functions as a reactive synthon for its tautomer, the three-coordinate, trisamide species Nb(N[Np]Ar)3 (2). Treatment of 1 with various small molecules has demonstrated its capacity to effect two-electron reduction chemistry. Most noteworthy is the reaction between 1 and elemental phosphorus (P4), providing in high yield the bridging diphosphide complex (mu2:eta2,eta2-P2)[Nb(N[Np]Ar)3]2. However, unsaturated organic functionality including nitriles and aldehydes can insert into the Nb-H bond of 1, leaving the niobaziridine ring intact, thus demonstrating that dual pathways of reactivity are available to the niobaziridine-hydride functional group.

Journal Article↗
PubMed1995

Functional and DNA sequence divergence of the CYP71 gene family in higher plants.

During ripening of avocado (Persea americana), the CYP71A1 mRNA and protein accumulate to relatively high levels. Although the CYP71A1 gene was the first plant P450 to be cloned and sequenced, the functional role of this P450 remains obscure. Substrate studies have shown that CYP71A1 will metabolize various monoterpenes (nerol and geraniol), although these have not been detected in ripening fruit. Using DNA from a conserved domain of the CYP71A1 gene, we have explored the scope of the CYP71 (or related) gene family in avocado using low stringency DNA hybridization. This analysis suggests that there are approximately 10-12 genes in the CYP71 family. An alternative approach using PCR gave essentially identical results.

Base Sequence↗
PubMed2001

Molecular and functional evidence for early divergence of an endothelin-like system during metazoan evolution: analysis of the Cnidarian, hydra.

A novel putative endothelin-converting enzyme (ECE) has been cloned from hydra, a freshwater invertebrate that belongs to the second oldest phylum of the animal kingdom. As an integral component of the endothelin system, vertebrate ECE functions in the activation of endothelin (ET) peptides. Vertebrate ETs are (1) the most potent vasoconstrictors known in mammals; and (2) function as essential signaling ligands during development of tissues derived from neural crest cells. To date, only a limited number of immunocytochemical studies have suggested the presence of endothelin-like peptides in invertebrates. Based on structural and functional analyses, we present evidence for a functional endothelin-like system in hydra that is involved in both muscle contraction and developmental processes. These findings indicate the broad use of endothelin systems in metazoans and also indicate that this type of signaling system arose early in evolution even before divergence of protostomes and deuterostomes.

Amino Acid Sequence↗
PubMed2002

Structure and function of an early divergent form of laminin in hydra: a structurally conserved ECM component that is essential for epithelial morphogenesis.

As a major component of the extracellular matrix (ECM), laminin has been found in many vertebrate and invertebrate organisms. Its molecular structure is very similar across species lines and its biological function in the ECM has been extensively studied. In an effort to study ECM structure and function in hydra, we have cloned a partial hydra laminin alpha chain and the full-length hydra laminin beta chain using ECM-enriched cDNA libraries. Analysis of deduced amino acid sequences indicated that both polypeptides have high sequence similarity to a number of invertebrate and vertebrate laminin alpha and beta subunits. Rotary shadow analysis of isolated hydra laminin indicates it has a heterotrimeric organization that is characteristic of vertebrate laminins. A putative integrin-class protein was also identified using a cell-binding peptide sequence from the laminin beta chain as an affinity probe, indicating that integrins are possible cell surface receptors in hydra. In agreement with previous results for the hydra laminin beta chain, in situ hybridization experiments revealed that hydra laminin alpha chain mRNA is restricted to endodermal cells. As with a number of other hydra ECM components, higher levels of laminin alpha chain mRNA are localized to regions where cell migration and differentiation are actively undertaken such as the base of tentacles, the peduncle region, buds, regenerating tentacles, and at the head end during regeneration. The role of laminin in morphogenesis was studied using an antisense approach and the results indicated that translation of the laminin alpha chain is required for head regeneration.

Amino Acid Sequence↗
PubMed2006

Conservation patterns in different functional sequence categories of divergent Drosophila species.

We have explored the distributions of fully conserved ungapped blocks in genome-wide pair-wise alignments of recently completed species of Drosophila: D. melanogaster, D. yakuba, D. ananassae, D. pseudoobscura, D. virilis, and D. mojavensis. Based on these distributions we have found that nearly every functional sequence category possesses its own distinctive conservation pattern, sometimes independent of the overall sequence conservation level. In the coding and regulatory regions, the ungapped blocks were longer than in introns, UTRs, and nonfunctional sequences. At the same time, the blocks in the coding regions carried a 3N + 2 signature characteristic of synonymous substitutions in the third-codon position. Larger block sizes in transcription regulatory regions can be explained by the presence of conserved arrays of binding sites for transcription factors. We also have shown that the longest ungapped blocks, or "ultraconserved" sequences, are associated with specific gene groups, including those encoding ion channels and components of the cytoskeleton. We discuss how restraining conservation patterns may help in mapping functional sequence categories and improve genome annotation.

Animals↗
PubMed1982

Multiple abnormalities in immunoregulatory function of synovial compartment T cells in patients with rheumatoid arthritis. Recognition of a helper augmentation effect.

Analyses of the synovial tissue and fluid T lymphocytes obtained from patients with rheumatoid arthritis revealed multiple functional defects in the regulation of autologous blood B cell differentiation into cells secreting immunoglobulin. These abnormalities were not found in peripheral blood T lymphocytes from the same patients. Although the patients selected showed elevated levels of T cells expressing the T8 differentiation antigen as well as Ia antigens there was little demonstrable suppression of the blood B cell differentiation. Furthermore, the synovial T cells exhibited only minimal helper or inducer activity when tested in the same system. In contrast, patient's blood T lymphocytes gave levels of help and suppression that were not distinguishable from that of normal individuals. Co-culture experiments of blood and synovial T lymphocytes did not reveal any evidence for enhanced suppression; indeed, in most patients these co-cultures resulted in marked augmentation of helper function, a phenomenon designated "helper augmentation". These data provide evidence that rheumatoid synovial lymphocytes are characterized by marked abnormalities in immunoregulatory T cell function, including divergence of cellular activity from the immune function predicted by surface phenotype and a capacity for "helper augmentation", a novel T cell function in man.

Arthritis, Rheumatoid↗