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PubMed1997

Molecular evolution of angiosperm mitochondrial introns and exons.

Numbers of substitutions per site for 15 protein-coding genes and six introns of the plant mitochondria were estimated to compare modes and tempos of evolution between exons and introns, and numbers of insertions-deletions per site also were investigated in introns. Intra-gene homogeneity of numbers of substitutions per site was assessed further among different taxa and between mitochondrial and nuclear paralogs translocated from the mitochondrial genome. Gene-to-gene differences in numbers of substitutions per site were found to be higher for nonsynonymous than synonymous sites, and this could be due to differential selection if mutation rate is assumed constant for the genome. Some mitochondrial genes have evolved as fast as chloroplast genes, thus faster than previously thought. For coxI, relative rate tests showed that woody taxa evolved slower than annuals at synonymous sites. Generation time, population size, and speciation rate are likely factors involved in this rate heterogeneity. Introns were less constrained than their adjacent exons for both overall numbers of substitutions per site and indels, but, on average, overall numbers of substitutions per site for introns were similar to numbers of synonymous substitutions per site for exons. Correlations were generally high between numbers of substitutions and numbers of indels per site for the same intron. Mitochondrial genes transferred to the nucleus had an accelerated rate of substitution per site, which was most significant at synonymous sites. These differences between paralogs in two different genomes are likely the result of different mutation rates.

DNA, Mitochondrial↗
PubMed2000

Heat shock protein 60 sequence comparisons: duplications, lateral transfer, and mitochondrial evolution.

Heat shock proteins 60 (GroEL) are highly expressed essential proteins in eubacterial genomes and in eukaryotic organelles. These chaperone proteins have been advanced as propitious marker sequences for tracing the evolution of mitochondrial (Mt) genomes. Similarities among HSP60 sequences based on significant segment pair alignment calculations are used to deduce associations of sequences taking into account GroEL functional/structural domain differences and to relate HSP60 duplications pervasive in alpha-proteobacterial lineages to the dynamics of lateral transfer and plasmid integration. Multiple alignments with consensuses are determined for 10 natural groups. The group consensuses sharpen the similarity contrasts among individual sequences. In particular, the Mt group matches best with the classical alpha-proteobacteria and closely with Rickettsia but significantly worse with the rickettsial groups Ehrlichia and Orientia. However, across broad protein sequence comparisons, there appears to be no consistent prokaryote whose protein sequences align best with animal Mt genomes. There are plausible scenarios indicating that the nuclear-encoded HSP60 (and HSP70) sequences functioning in Mt are results of lateral transfer and are probably derived from an alpha-proteobacterium. This hypothesis relates to the plethora of duplicated HSP60 sequences among the classical alpha-proteobacteria contrasted with no duplications of HSP60 among other clades of proteobacterial genomes. Evolutionary relations are confounded by differential selection pressures, convergence, variable mutational rates, site variability, and lateral gene transfer.

Bacteria↗
PubMed1996

Compartmental isolation of cholesterol participating in the cytoplasmic cholesteryl ester cycle in Chinese hamster ovary 25-RA cells.

Using the Chinese hamster ovary cell line, 25-RA, we have demonstrated that lipoprotein-derived cholesterol and endogenously synthesized cholesterol are selectively differentiated with respect to their cellular locations. These cells lack sterol-mediated regulation, spontaneously storing large amounts of esterified cholesterol, which turns over with a half-time of 7.5 h. When [3H]cholesterol was provided to the cells in serum to trace cellular cholesterol, the specific activities of cellular free and esterified cholesterol (6238 +/- 273 and 5128 +/- 277 cpm/ microg, respectively) failed to equilibrate, indicating that bulk cellular free cholesterol is isolated from that participating in the cholesteryl ester cycle. Using [3H]acetate to trace the fate of endogenously synthesized cholesterol, a failure of equilibration was also observed (specific activities of free and esterified cholesterol = 280 +/- 37 and 458 +/- 8 cpm/ microg, respectively). The lower specific activity of the precursor indicates that endogenously synthesized cholesterol is preferentially esterified. When cells radiolabeled with [3H]acetate were post-incubated in the absence of radiolabel, the specific activity of the esterified cholesterol pool remained significantly higher than that of the free cholesterol, suggesting that cholesterol derived from hydrolysis of esterified cholesterol is preferentially re-esterified.

Acetates↗
PubMed2000

Highly hydrophilic proteins in prokaryotes and eukaryotes are common during conditions of water deficit.

The late embryogenesis abundant (LEA) proteins are plant proteins that are synthesized at the onset of desiccation in maturing seeds and in vegetative organs exposed to water deficit. Here, we show that most LEA proteins are comprised in a more widespread group, which we call "hydrophilins." The defining characteristics of hydrophilins are high glycine content (>6%) and a high hydrophilicity index (>1.0). By data base searching, we show that this criterion selectively differentiates most known LEA proteins as well as additional proteins from different taxons. We found that within the genomes of Escherichia coli and Saccharomyces cerevisiae, only 5 and 12 proteins, respectively, meet our criterion. Despite their deceivingly loose definition, hydrophilins usually represent <0.2% of the proteins of a genome. Additionally, we demonstrate that the criterion that defines hydrophilins seems to be an excellent predictor of responsiveness to hyperosmosis since most of the genes encoding these proteins in E. coli and S. cerevisiae are induced by osmotic stress. Evidence for the participation of one of the E. coli hydrophilins in the adaptive response to hyperosmotic conditions is presented. Apparently, hydrophilins represent analogous adaptations to a common problem in such diverse taxons as prokaryotes and eukaryotes.

Algorithms↗
PubMed2004

Binding specificity of sea anemone toxins to Nav 1.1-1.6 sodium channels: unexpected contributions from differences in the IV/S3-S4 outer loop.

Sea anemones are an important source of various biologically active peptides, and it is known that ATX-II from Anemonia sulcata slows sodium current inactivation. Using six different sodium channel genes (from Nav1.1 to Nav1.6), we investigated the differential selectivity of the toxins AFT-II (purified from Anthopleura fuscoviridis) and Bc-III (purified from Bunodosoma caissarum) and compared their effects with those recorded in the presence of ATX-II. Interestingly, ATX-II and AFT-II differ by only one amino acid (L36A) and Bc-III has 70% similarity. The three toxins induced a low voltage-activated persistent component primarily in the Nav1.3 and Nav1.6 channels. An analysis showed that the 18 dose-response curves only partially fit the hypothesized binding of Lys-37 (sea anemone toxin Anthopleurin B) to the Asp (or Glu) residue of the extracellular IV/S3-S4 loop in cardiac (or nervous) Na+ channels, thus suggesting the substantial contribution of some nearby amino acids that are different in the various channels. As these channels are atypically expressed in mammalian tissues, the data not only suggest that the toxicity is highly dependent on the channel type but also that these toxins and their various physiological effects should be considered prototype models for the design of new and specific pharmacological tools.

Amino Acid Sequence↗
PubMed2004

Genetic dissection of the phospholipid hydroperoxidase activity of yeast gpx3 reveals its functional importance.

Saccharomyces cerevisiae expresses multiple phospholipid hydroperoxide glutathione peroxidase (PHGPx)-like proteins in the absence of a classical glutathione peroxidase (cGPx), providing a unique system for dissecting the roles of these enzymes in vivo. The Gpx3 (Orp1/PHGpx3) protein transduces the hydroperoxide signal to the transcription factor Yap1, a function that could account for most GPX-dependent phenotypes. To test this hypothesis and ascertain what functions of Gpx3 can be shared by cGPx-like enzymes, we constructed a novel cGPx-like yeast enzyme, cGpx3. We confirmed that the "gap" sequences conserved among cGPxs but absent from aligned PHGPx sequences are the principal cause of the structural and functional differences of these enzymes. Peroxidase activity against a cGPx substrate was high in the cGpx3 construct, which was multimeric and had a peroxidase catalytic mechanism distinct from Gpx3; but cGpx3 was defective for phospholipid hydroperoxidase and signaling activities. cGpx3 did not complement the sensitivity to lipid peroxidation of a gpxDelta mutant, and the resistance to lipid peroxidation conferred by Gpx3 was independent of Yap1, establishing a functional role for Gpx3 phospholipid hydroperoxidase activity. Using the comparison between cGpx3 and Gpx3 in conjunction with other constructs to probe lipid peroxidation as a toxicity mechanism, we also ascertained that lipid peroxidation-dependent processes are a principal cause of cellular cadmium toxicity. The results demonstrate that phospholipid hydroperoxidase and Yap1-mediated signaling activities of Gpx3 have independent functional roles, although both functions depend on the absence of cGPx-like subunit interaction sites, and the results resolve more clearly the potential drivers of the differential selective evolution of GPx-like enzymes.

Alternative Splicing↗
PubMed2006

Hu proteins regulate polyadenylation by blocking sites containing U-rich sequences.

A recent genome-wide bioinformatic analysis indicated that 54% of human genes undergo alternative polyadenylation. Although it is clear that differential selection of poly(A) sites can alter gene expression, resulting in significant biological consequences, the mechanisms that regulate polyadenylation are poorly understood. Here we report that the neuron-specific members of a family of RNA-binding proteins, Hu proteins, known to regulate mRNA stability and translation in the cytoplasm, play an important role in polyadenylation regulation. Hu proteins are homologs of the Drosophila embryonic lethal abnormal visual protein and contain three RNA recognition motifs. Using an in vitro polyadenylation assay with HeLa cell nuclear extract and recombinant Hu proteins, we have shown that Hu proteins selectively block both cleavage and poly(A) addition at sites containing U-rich sequences. Hu proteins have no effect on poly(A) sites that do not contain U-rich sequences or sites in which the U-rich sequences are mutated. All three RNA recognition motifs of Hu proteins are required for this activity. Overexpression of HuR in HeLa cells also blocks polyadenylation at a poly(A) signal that contains U-rich sequences. Hu proteins block the interaction between the polyadenylation cleavage stimulation factor 64-kDa subunit and RNA most likely through direct interaction with poly(A) cleavage stimulation factor 64-kDa subunit and cleavage and polyadenylation specificity factor 160-kDa subunit. These studies identify a novel group of mammalian polyadenylation regulators. Furthermore, they define a previously unknown nuclear function of Hu proteins.

Animals↗
PubMed2000

Drinking during pregnancy: practices of Cambodian refugees in France and the United States.

This study is part of a larger exploratory study of 155 women of Cambodian national origin who were interviewed in the United States and France. This study reports on data related to frequency of alcohol usage, prevalence of drinking over the trimesters of pregnancy, beverage of choice, whether they spoke either English or French when leaving Cambodia, years of education, and current income. In this sample, Cambodian women residing in France drank more frequently, and drank different substances than those women residing in the United States. With respect to drinking during pregnancy, 37% of the women in France and 23% of the women residing in the United States drank in the first trimester. During the second and third trimesters, however, only 5% of the women in France, compared with 18% of women in the United States, continued drinking. It is suggested that different cultural practices in France and the United States account for differences in initial drinking practices. Three possible explanations were suggested to account for the fact that more Cambodian women residing in the United States, as compared with France, reported continued drinking over the course of their pregnancies: more limited health care access, differential selection policies for admittance, and lower overall socioeconomic status (SES). All French women, unlike American women, are covered by a comprehensive program of maternal and child health care. In addition, the Cambodian women residing in France were older, had more years of education, higher incomes, and a greater percentage spoke French before they left Cambodia. The results emphasize the relationship of socioeconomic factors to substance use and point toward a need for programs designed to educate Cambodian women with respect to the problems associated with drinking during pregnancy.

Adult↗
PubMed2005

A chemical polymorphism in a multitrophic setting: thyme monoterpene composition and food web structure.

We investigated the effects of chemical variation in thyme (Thymus vulgaris L.) on its interactions with competitors, herbivores, and herbivore predators. Four different thyme monoterpene phenotypes (chemotypes) were grown in a 4x2x2 factorial of chemotype, caging (sham half-cages vs. full cages), and competition (control vs. the grass Bromus madritensis L.). Cages reduced numbers of arthropod predators. Thyme-feeding aphids Aphis serpylli Koch passed through full cage walls to increase more than fourfold. As a result, freed from their predators, aphids had a large negative effect on thyme size and flowering. Similarly, competition from Bromus had a negative effect on thyme size and flowering. Individual effects of aphids and competition were nonadditive, however, and their combined effect was significantly less than that predicted by a multiplicative null model. Differential thyme sizes among chemotypes were not mediated by herbivores or competitors, but differential flowering was due to the effects of chemotype on aphids. We thus document differential selection by aphids among thyme chemotypes and the influence of Bromus on the strength of these negative effects of aphids.

Animal Feed↗
PubMed2005

A novel method for somatic cell nuclear transfer to mouse embryonic stem cells.

Nuclear reprogramming by somatic cell nuclear transfer (SCNT) provides a practical approach for generating autologous pluripotent cells from adult somatic cells. It has been shown that murine somatic cells can also be reprogrammed to a pluripotent-like state by fusion with embryonic stem (ES) cells. Typically, the first step in SCNT involves enucleation of the recipient cell. However, recent evidence suggests that enucleated diploid ES cells may lack reprogramming capabilities. Here we have developed methods whereby larger tetraploid ES cells are first generated by fusion of two mouse ES cell lines transfected with plasmids carrying different antibiotic-resistance cassettes, followed by double antibiotic selection. Tetraploid ES cells grown on tissue culture disks or wells can be efficiently enucleated (up to 99%) using a combination of cytochalasin B treatment and centrifugation, with cytoplasts generated from these cells larger than those obtained from normal diploid ES cells. Also, we show that the enucleation rate is dependent on centrifugation time and cell ploidy. Further, we demonstrate that normal diploid ES cells can be fused to tetraploid ES cells to form heterokaryons, and that selective differential centrifugation conditions can be applied where the tetraploid nucleus is removed while the diploid donor nucleus is retained. This technology opens new avenues for generating autologous, diploid pluripotent cells, and provides a dynamic model for studying nuclear reprogramming in ES cells.

Animals↗
PubMed2004

Prevalence of the internalization-associated gene prtF1 in a bacterial population of Streptococcus pyogenes isolated from children with acute pharyngotonsillitis before and after antibiotic therapy.

The prevalence of the internalization-associated prtF1 gene was studied in 837 isolates of Streptococcus pyogenes obtained from 713 pediatric patients presenting with acute pharyngotonsillitis before and after antibiotic therapy. Its association with macrolide resistance and with bacteriological treatment failure was determined. The bacterial population isolated from baseline pharyngeal swabs showed an overall prtF1 positivity rate of 33%. A higher prtF1 positivity was found among erythromycin-resistant strains (45%) showing, however, marked differences between the inducible (iMLS), constitutive (cMLS), and efflux pump (M) resistance phenotypes. The prevalence was statistically higher (p < 0.001) in strains belonging to iMLS (84%) and cMLS (67%) phenotypes as compared to the M phenotype (15%). Interestingly, the prevalence of the prtF1 gene was significantly lower (p = 0.04) in strains belonging to M resistance phenotype as compared to erythromycin-susceptible strains (28%). Failed bacterial eradication was demonstrated in 124 patients. The prtF1 positivity rate remained unchanged in strains isolated before and after therapy in patients treated with macrolides (9/54). On the other hand, the positivity rate for the prtF1 gene was significantly higher (p = 0.015) in strains isolated after therapy with beta-lactams (21/70) as compared to baseline isolates (6/70), indicating a differential selection imposed on the organism by these agents. Finally, a high overall eradication rate (88%) of prtF1-positive isolates, belonging to both the erythromycin-susceptible and -resistant phenotypes, was demonstrated following macrolide treatment.

Acute Disease↗
PubMed1995

Molecular evolution of the Ac/Ds transposable-element family in pearl millet and other grasses.

We report an Ac-like sequence from pearl millet (Pennisetum glaucum) and deletion derivative Ac-like sequences from pearl millet and another grass species, Bambusa multiplex. Sequence relationships between the pearl millet and maize Ac elements suggest that Ac/Ds transposable-element family is ancient. Further, the sequence identity between the Bambusa Ac-like sequence and maize Ac implies that the Ac/Ds transposable-element family has been in the grass family since its inception. The Ac-like sequences reported from pearl millet and maize Ac are statistically heterogeneous in pair-wise distance comparisons to each other. Yet, we are unable to discriminate between differential selection or ectopic exchange (recombination and conversion) between nonidentical transposable element homologues, as the cause of the heterogeneity. However, the more extreme heterogeneity exhibited between the previously described pearl millet element and maize Ac seems likely to derive from ectopic exchange between elements with different levels of divergence.

Base Sequence↗
PubMed1996

Synonymous substitutions in the Xdh gene of Drosophila: heterogeneous distribution along the coding region.

The Xdh (rosy) region of Drosophila subobscura has been sequenced and compared to the homologous region of D. pseudoobscura and D. melanogaster. Estimates of the numbers of synonymous substitutions per site (Ks) confirm that Xdh has a high synonymous substitution rate. The distributions of both nonsynonymous and synonymous substitutions along the coding region were found to be heterogeneous. Also, no relationship has been detected between Ks estimates and codon usage bias along the gene, in contrast with the generally observed relationship among genes. This heterogeneous distribution of synonymous substitutions along the Xdh gene, which is expression-level independent, could be explained by a differential selection pressure on synonymous sites along the coding region acting on mRNA secondary structure. The synonymous rate in the Xdh coding region is lower in the D. subobscura than in the D. pseudoobscura lineage, whereas the reverse is true for the Adh gene.

Animals↗
PubMed2001

The spatial structure of sexual and cytonuclear polymorphism in the gynodioecious Beta vulgaris ssp. maritima: I/ at a local scale.

We have analyzed the spatial distribution of the sex phenotypes and of mitochondrial, chloroplast, and nuclear markers within two gynodioecious populations of Beta vulgaris ssp. maritima. Within both populations, sexual phenotype variation is controlled mainly by the cytoplasmic genotype, although in one study population a joint polymorphism of cytonuclear factors is clearly involved. In spite of contrasts in the ecology (mainly due to different habitats), a clear common feature in both populations is the highly patchy distribution of cytoplasmic haplotypes, contrasting with the wide distribution of nuclear diversity. This high contrast between cytoplasmic vs. nuclear spatial structure may have important consequences for the maintenance of gynodioecy. It provides opportunities for differential selection since nuclear restorer alleles are expected to be selected for in the presence of their specific cytoplasmic male sterile (CMS) type, but to be neutral (or selected against if there is a cost of restoration) in the absence of their CMS type. Selective processes in such a cytonuclear landscape may explain the polymorphism we observed at restorer loci for two CMS types.

Cell Nucleus↗
PubMed1995

Characterization of the Culex pipiens complex (Diptera: Culicidae) in Madagascar.

Morphological analysis of phallosome and multilocus electrophoresis were used to characterize populations of the Culex pipiens L. complex from Madagascar. Samples phenotypically and genetically corresponding to Cx. p. quinquefasciatus Say were found on the east and west coasts, whereas, on the high plateau, 1 sample was composed mostly of phenotypical Cx. p. pipiens L., genetically introgressed with quinquefasciatus at some loci (Hbdh, Aat-2, and Hk-1). A hybrid zone between the 2 taxa was detected on the plateau on a genetic basis, whereas at the morphological level a predominance of Cx. p. quinquefasciatus specimens and deficit of intermediates was observed. Accordingly, morphological analysis failed to describe satisfactorily the hybridization phenomena. Despite the high level of gene exchange, a complete mixing of the 2 gene pools apparently does not occur, possibly because of differential selective pressures in the climatically heterogeneous environment of the Madagascar plateau.

Animals↗
PubMed2003

Nonrandom distribution of alu elements in genes of various functional categories: insight from analysis of human chromosomes 21 and 22.

The first draft of the human genome has revealed enormous variability in the global distribution of Alu repeat elements. There are regions such as the four homeobox gene clusters, which are nearly devoid of these repeats that contrast with repeat dense regions in other transcriptionally active regions of the genome. Our analysis of the completely sequenced chromosomes 21 and 22 revealed a striking bias in Alu distribution. These elements are more clustered in genes which are involved in metabolism, transport, and signaling processes. In contrast, they are significantly fewer in genes coding for information pathway components as well as structural proteins. This bias in Alu distribution is independent of the effect of Alu density of the flanking genomic region and is also not affected by the GC content of the gene and its upstream and downstream regions. The relative proportions of Alu subfamilies (Alu J, Alu S, and Alu Y) are not significantly different in genes with high Alu density belonging to the functional categories of transport, metabolism, and signaling. However, in the structural proteins and information genes, these proportions are lower than the other three categories. We suggest that Alu elements might be involved in regulatory mechanisms and are therefore differentially selected in primate genomes.

Alu Elements↗
PubMed1993

cDNA structure, expression and nucleic acid-binding properties of three RNA-binding proteins in tobacco: occurrence of tissue-specific alternative splicing.

Three cDNAs encoding RNA-binding proteins were isolated from a tobacco (Nicotiana sylvestris) cDNA library. The predicted proteins (RGP-1) are homologous to each other and consist of a consensus-sequence type RNA-binding domain of 80 amino acids in the N-terminal half and a glycine-rich domain of 61-78 amino acids in the C-terminal half. Nucleic acid-binding assay using the in vitro synthesized RGP-1 protein confirmed that it is an RNA-binding protein. Based on its strong affinity for poly(G) and poly(U), the RGP-1 proteins are suggested to bind specifically to G and/or U rich sequences. All three genes are expressed in leaves, roots, flowers and cultured cells, however, the substantial amount of pre-mRNAs are accumulated especially in roots. Sequence analysis and ribonuclease protection assay indicated that significant amounts of alternatively spliced mRNAs, which are produced by differential selection of 5' splice sites, are also present in various tissues. Tissue-specific alternative splicing was found in two of the three genes. The alternatively spliced mRNAs are also detected in polysomal fractions and are suggested to produce truncated polypeptides. A possible role of this alternative splicing is discussed.

Alternative Splicing↗
PubMed1993

Regional base composition variation along yeast chromosome III: evolution of chromosome primary structure.

The recent determination of the complete sequence of chromosome III from the yeast Saccharomyces cerevisiae allows, for the first time, the investigation of the long range primary structure of a eukaryotic chromosome. We have found that, against a background G+C level of about 35%, there are two regions (one in each chromosome arm) in which G+C values rise to over 50%. This effect is seen in silent sites within genes, but not in noncoding intergenic sequences. The variation in G+C content is not related to differential selection of synonymous codons, and probably reflects mutational biases. That the intergenic regions do not exhibit the same phenomenon is particularly interesting, and suggests that they are under substantial constraint. The yeast chromosome may be a model of the structure of the human genome, since there is evidence that it is also a mosaic of long regions of different base compositions, reflected in wide variation of G+C content at silent sites among genes. Two possible causes of this regional effect, replication timing, and recombination frequency, are discussed.

Animals↗