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At least 829 records · Page 46Linked to original sources
PubMed2000

Nucleotide bias causes a genomewide bias in the amino acid composition of proteins.

We analyzed the nucleotide contents of several completely sequenced genomes, and we show that nucleotide bias can have a dramatic effect on the amino acid composition of the encoded proteins. By surveying the genes in 21 completely sequenced eubacterial and archaeal genomes, along with the entire Saccharomyces cerevisiae genome and two Plasmodium falciparum chromosomes, we show that biased DNA encodes biased proteins on a genomewide scale. The predicted bias affects virtually all genes within the genome, and it could be clearly seen even when we limited the analysis to sets of homologous gene sequences. Parallel patterns of compositional bias were found within the archaea and the eubacteria. We also found a positive correlation between the degree of amino acid bias and the magnitude of protein sequence divergence. We conclude that mutational bias can have a major effect on the molecular evolution of proteins. These results could have important implications for the interpretation of protein-based molecular phylogenies and for the inference of functional protein adaptation from comparative sequence data.

Amino Acids↗
PubMed1972

Compositional heterogeneity of human heterochromatin.

When human genome was fractionated by thermal elution chromatography, repetitious DNA was found in every arbitrary temperature segment. When these repetitious DNA families were used for in situ hybridization, the following conclusions were evident: (a) Unlike the case of mouse, where essentially all centromeric heterochromatins appear to be composed of one DNA family, human heterochromatin is composed of various DNA families. (b) Some human heterochromatin pieces, (e.g., that of chromosome 9) appear to have more heterogeneous composition than others (e.g., that of chromosome 1). (c) The highly repetitious human DNA fractions are located primarily at the centromeric and telomeric regions, but the interstitial regions also contain these fractions. (d) The more slowly reassociating repetitious sequences are distributed over the length of the chromatid, with a slight bias in favor of the telomeric regions. (e) The repetitious DNA fractions of higher (guanine + cytosine) content have less affinity for the centromeric regions.

Cells, Cultured↗
PubMed2005

How to be moderately halophilic with broad salt tolerance: clues from the genome of Chromohalobacter salexigens.

We analyzed the amino acid composition of different categories of proteins of the moderately halophilic bacterium Chromohalobacter salexigens, as deduced from its genome sequence. Comparison with non-halophilic representatives of the gamma-Proteobacteria (Escherichia coli, Pseudomonas aeruginosa, Vibrio cholerae) shows only a slight excess of acidic residues in the cytoplasmic proteins, and no significant differences were found in the acidity of membrane-bound proteins. In contrast, a very pronounced difference in mean pI value was observed for the periplasmic binding proteins of the ABC transport systems of C. salexigens and the non-halophiles E. coli and P. aeruginosa. V. cholerae, which is adapted to life in brackish water, showed intermediate values. The findings suggest that there is a major difference between the proteins of the moderate halophile C. salexigens and non-halophilic bacteria in their periplasmic proteins, exemplified by the substrate binding proteins of transport systems. The highly acidic nature of these proteins may enable them to function at high salt concentrations. The evolution of highly salt-tolerant prokaryotes may have depended on an increase in acidity of the proteins located external to the cytoplasmic membrane, enabling effective transport of nutrients into the cell.

Amino Acids↗
PubMed2001

Protein surface amino acid compositions distinctively differ between thermophilic and mesophilic bacteria.

One of the well-known observations of proteins from thermophilic bacteria is the bias of the amino acid composition in which charged residues are present in large numbers, and polar residues are scarce. On the other hand, it has been reported that the molecular surfaces of proteins are adapted to their subcellular locations, in terms of the amino acid composition. Thus, it would be reasonable to expect that the differences in the amino acid compositions between proteins of thermophilic and mesophilic bacteria would be much greater on the protein surface than in the interior. We performed systematic comparisons between proteins from thermophilic bacteria and mesophilic bacteria, in terms of the amino acid composition of the protein surface and the interior, as well as the entire amino acid chains, by using sequence information from the genome projects. The biased amino acid composition of thermophilic proteins was confirmed, and the differences from those of mesophilic proteins were most obvious in the compositions of the protein surface. In contrast to the surface composition, the interior composition was not distinctive between the thermophilic and mesophilic proteins. The frequency of the amino acid pairs that are closely located in the space was also analyzed to show the same trend of the single amino acid compositions. Interestingly, extracellular proteins from mesophilic bacteria showed an inverse trend against thermophilic proteins (i.e. a reduced number of charged residues and rich in polar residues). Nuclear proteins from eukaryotes, which are known to be abundant in positive charges, showed different compositions as a whole from the thermophiles. These results suggest that the bias of the amino acid composition of thermophilic proteins is due to the residues on the protein surfaces, which may be constrained by the extreme environment.

Amino Acids↗
PubMed2025

The evolution of the plastid genomes in the holoparasitic Balanophoraceae.

The independent transition to a heterotrophic lifestyle in plants drove remarkably convergent evolutionary trajectories, characterized by morphological modifications and reductions in their plastomes. The characteristics of the minimum plastome required for survival, if they exist, remain a topic of debate. The holoparasitic family Balanophoraceae was initially presumed to have entirely lost their plastids, however, recent reports revealed the presence of reduced and aberrant plastids with odd genomes. Among the outstanding features of these genomes are the highest nucleotide composition bias across the tree of life and the only two genetic code changes ever recorded among plants. In this study, we assembled the plastomes from five genera, four of which had never been studied. Major common features include extremely high AT content, the lack of a typical quadripartite structure and extensive size reduction due to gene elimination and genome compaction. The family exhibits multiple gene and intron losses, and a broad range of scenarios regarding the evolution of the plastid trnE, a gene considered essential because of its dual function in tetrapyrrole biosynthesis and translation within the plastid. In addition, phylogenetic analyses suggest that the genus Scybalium is not monophyletic. An evolutionary model for the plastomes of the Balanophoraceae is proposed.

Genome, Plastid↗
PubMed2026

Longitudinal analysis of genomic and immune differences between primary and metastatic nasopharyngeal carcinoma for precision oncology.

INTRODUCTION: Nasopharyngeal carcinoma (NPC) is a common malignancy with a high incidence in Southern China and Southeast Asia. Distant metastasis remains a major cause of poor prognosis. This study aims to explore the genomic and immune microenvironmental changes in primary and metastatic NPC through longitudinal analysis, to provide insights for guiding precision treatment strategies. METHODS: We analyzed tumor samples from 11 male NPC patients with distant metastasis. Paired primary and metastatic samples underwent targeted whole-exome sequencing (551 genes) and RNA sequencing (289 genes). Multiplex immunohistochemistry was performed to assess immune cell composition and immune response markers. Genomic alterations and immune features were compared between primary and metastatic tumors, and their associations with clinical outcomes were evaluated. RESULTS: Metastatic tumors exhibited distinct chromosomal changes, including frequent 1q gain, while 6p gain showed a trend toward prolonged survival. Primary tumors showed stronger immune suppression characterized by increased B-cell and Treg infiltration and elevated CTLA4 and IDO1 expression, whereas metastatic lesions displayed more active immune responses. Liver metastases presented a distinct immune landscape with lower CD8+ T-cell density compared to non-liver metastases. In locoregionally advanced NPC, high expression of oncogenic genes such as EGFR and MYC correlated with shorter disease-free survival, while elevated PANCK expression and enhanced cytotoxicity were linked to better outcomes. These results delineate the molecular and immune evolution of NPC and provide a foundation for developing precision therapeutic strategies. CONCLUSION: This study identifies key molecular and immune features associated with NPC survival. Primary tumors show an immunosuppressive phenotype, suggesting potential benefits from combining CTLA4 or IDO1 inhibitors with PD-1 blockade. Liver metastases exhibit distinct immune features, supporting the need for site-specific precision therapies. These findings contribute to personalized management strategies in NPC, guiding treatment based on molecular and immune profiles.

distant metastasis↗
PubMed1991

Novel anticodon composition of transfer RNAs in Micrococcus luteus, a bacterium with a high genomic G + C content. Correlation with codon usage.

The number and relative amount of isoacceptor tRNAs for each amino acid in Micrococcus luteus, a Gram-positive bacterium with high genomic G + C content, have been determined by sequencing their anticodon loop and its adjacent regions and by selective labelling of tRNAs. Thirty-one tRNA species with 29 different anticodon sequences have been detected. All the tRNAs have G or C at the anticodon first position except for tRNA(ICGArg) and tRNA(NGASer), in response to the abundant usage of NNC and NNG codons. No tRNA with the anticodon UNN capable of translating codon NNA has been detected, in accordance with a very low or zero usage of NNA codons. The relative amount of isoacceptor tRNAs for an amino acid determined by selective labelling strongly correlates with usage of the corresponding codons. On the basis of these and other observations in this and other eubacterial species, we conclude that the relative amount and anticodon composition of isoacceptor tRNA species are flexible, and their changes are mainly adaptive phenomena that have been primarily affected by codon usage, which in turn is affected by directional mutation pressure.

Anticodon↗
PubMed2002

Compensation for nucleotide bias in a genome by representation as a discrete channel with noise.

MOTIVATION: Calculation of the information content of motifs in genomes highly biased in nucleotide composition is likely to lead to overestimates of the amount of useful information in the motif. Calculating relative information can compensate for biases, however the resulting information content is the amount seen by an observer and not by a macromolecule binding to the motif. The latter is needed to calculate the discriminatory power of the motif and to compare motifs between species. RESULTS: By treating a biased genome as a discrete channel with noise, in accordance with Shannon Information Theory, we were able to remove both 'Distortion' and 'Noise' from the motif and recover a more instructive biological 'signal.' A Java application, LogoPaint, was developed to remove nucleotide bias distortion and triplet frequency noise from motifs, calculate information content and present the motif as a logo. We demonstrate how this technique can 'unmask' motifs in the translation initiation regions of bacteria that are obscured by strong sequence biases. AVAILABILITY: LogoPaint is available to all users from the authors as an executable JAR file. Source code is available by arrangement.

Algorithms↗
PubMed1999

Delta 9-fatty acid desaturase from arachidonic acid-producing fungus. Unique gene sequence and its heterologous expression in a fungus, Aspergillus.

Based on the sequence information for delta 9-desaturase genes (from rat, mouse and yeast), which are involved in the desaturation of palmitic acid and stearic acid to palmitoleic acid and oleic acid, respectively, the corresponding cDNA and genomic gene were cloned from the fungal strain, Mortierella alpina 1S-4, which industrially produces arachidonic acid. There was a cytochrome b5-like domain linked to the carboxyl terminus of this Mortierella desaturase, as also seen in the yeast delta 9-desaturase. The Mortierella delta 9-desaturase genomic gene had only one intron, in which a novel phenomenon was observed: there was a GC-end at the 5'-terminus instead of a GT-end that is, in general, found in introns of eukaryotic genes. The full-length cDNA clone was expressed under the control of an amyB promoter in a filamentous fungus, Aspergillus oryzae, resulting in drastic changes in the fatty acid composition in the transformant cells; the contents of palmitoleic acid (16:1) and oleic acid (18:1) increased significantly, with accompanying decreases in palmitic acid (16:0) and stearic acid (18:0). These changes were controlled by the addition of maltose as a carbon source to the medium. Also, the expression of the gene caused a significant change in the lipid composition in the Aspergillus transformant. Genomic Southern blot analysis of the transformant with the Mortierella delta 9-desaturase gene as a probe confirmed the integration of this gene into the genome of A. oryzae.

Amino Acid Sequence↗
PubMed1999

Evolutionary genomics in Metazoa: the mitochondrial DNA as a model system.

One of the most important aspects of mitochondrial (mt) genome evolution in Metazoa is constancy of size and gene content of mtDNA, whose plasticity is maintained through a great variety of gene rearrangements probably mediated by tRNA genes. The trend of mtDNA to maintain the same genetic structure within a phylum (e.g., Chordata) is generally accepted, although more recent reports show that a considerable number of transpositions are observed also between closely related organisms. Base composition of mtDNA is extremely variable. Genome GC content is often low and, when it increases, the two complementary bases distribute asymmetrically, creating, particularly in vertebrates, a negative GC-skew. In mammals, we have found coding strand base composition and average degree of gene conservation to be related to the asymmetric replication mechanism of mtDNA. A quantitative measurement of mtDNA evolutionary rate has revealed that each of the various components has a different evolutionary rate. Non-synonymous rates are gene specific and fall in a range comparable to that of nuclear genes, whereas synonymous rates are about 22-fold higher in mt than in nuclear genes. tRNA genes are among the most conserved but, when compared to their nuclear counterparts, they evolve 100 times faster. Finally, we describe some molecular phylogenetic reconstructions which have produced unexpected outcomes, and might change our vision of the classification of living organisms.

Animals↗
PubMed2003

Eyeing bacterial genomes.

The density of information in a bacterial genome allows its history, organization and encoded functions to be distilled into a single graphical representation. These features have made it possible to discern the forces acting in and on bacterial genomes at levels not attainable in eukaryotes.

Bacteria↗
PubMed1997

Characterization of an interspersed repetitive DNA element in the genome of Trypanosoma cruzi.

We report the molecular characterization of a middle repetitive DNA sequence, named C6, isolated from the Trypanosoma cruzi genome. C6 appears to be a composite repeated element since 3 subregions may be defined within it on the basis of sequence similarities with other T. cruzi genomic sequences. Sequences homologous to C6 are interspersed in the genome and can be mapped out on most chromosomal bands of different T. cruzi. strains. The copy number of the C6 element is about 1000 per haploid genome. Given the species specificity and different genomic distribution of C6 homologous sequences among the T. cruzi strains the C6 element could be a useful probe for diagnosis and typing of parasites. C6 is a polymorphic marker with potential as a tool for physical mapping of the T. cruzi genome.

Animals↗
PubMed1976

Effect of membrane protein on lipid bilayer structure: a spin-label electron spin resonance study of vesicular stomatitis virus.

Spin-label electron spin resonance (ESR) methods have been used to study the structure of the envelope of vesicular stomatitis virus (VSV). The data indicate that the lipid is organized in a bilayer structure. Proteolytic digestion of the glycoproteins which are the spike-like projections on the outer surface of the virus particle increases the fluidity of the lipid bilayer. Since the lipid composition of the virion reflects the composition of the host plasma membrane and the protein composition is determined by the viral genome, VSV was grown in both MDBK and BHK21-F cells to determine the effect of a change in lipid composition on the structure of the lipid bilayer of VSV. The lipid bilayer of the virion was found to be more rigid when derived from MDBK cells than from BHK21-F cells. Studies comparing spin-labeled intact cells and cell membrane fractions suggest that upon labeling the whole cell the spin label probes the plasma membrane. Comparison of spin-labeled VSV particles and their host cells indicates that the lipid bilayer of the plasma membrane is considerably more fluid than that of the virion. These results are discussed in terms of the effect of membrane-associated protein on the structure of the lipid bilayer.

Binding Sites↗
PubMed2026

Motile and non-motile Listeria species adopt distinct ecological and evolutionary strategies to achieve broad geographic ranges across soil ecosystems.

Broad geographic ranges often reflect ecological versatility and are associated with lower extinction risk. Motility is a key physiological and ecological trait in bacteria. However, how some motile and non-motile bacteria achieve broad geographic ranges remains poorly understood. Here, we analyzed the genomes of 141 Listeria welshimeri and 90 Listeria booriae isolates systematically obtained from soils, representing widespread motile and non-motile species, respectively. We show that L. welshimeri lacks clear phylogeographic structure, suggesting minimal geographic barriers to dispersal. Its wide distribution is likely associated with enhanced motility and effective host colonization that facilitate wildlife-driven dispersal, particularly by regional-terrestrial birds. This pattern is supported by positive selection on flagellar and chemotaxis genes, strong associations with wildlife movement patterns, and close genomic relatedness between soil and wild bird isolates. In contrast, L. booriae displays clade endemism and a strong distance-decay relationship, suggesting dispersal limitation. Despite lacking a dispersal advantage, L. booriae's wide distribution appears to be linked to genomic flexibility and metabolic versatility that support adaptation to diverse environmental conditions, especially those shaped by iron concentration and precipitation. This is evidenced by its large, open pangenome characterized by abundant and diverse metabolic pathways and broad substrates utilization capacity; pronounced positive selection on genes involved in inorganic ion, amino acid, and coenzyme transport and metabolism; and strong associations between gene richness and abiotic factors as well as bacterial community composition. These findings suggest distinct genomic foundations and ecological and evolutionary mechanisms underlying the success of motile and non-motile cosmopolitan bacteria in soil ecosystems.

Soil Microbiology↗
PubMed2001

A computational approach to identify genes for functional RNAs in genomic sequences.

Currently there is no successful computational approach for identification of genes encoding novel functional RNAs (fRNAs) in genomic sequences. We have developed a machine learning approach using neural networks and support vector machines to extract common features among known RNAs for prediction of new RNA genes in the unannotated regions of prokaryotic and archaeal genomes. The Escherichia coli genome was used for development, but we have applied this method to several other bacterial and archaeal genomes. Networks based on nucleotide composition were 80-90% accurate in jackknife testing experiments for bacteria and 90-99% for hyperthermophilic archaea. We also achieved a significant improvement in accuracy by combining these predictions with those obtained using a second set of parameters consisting of known RNA sequence motifs and the calculated free energy of folding. Several known fRNAs not included in the training datasets were identified as well as several hundred predicted novel RNAs. These studies indicate that there are many unidentified RNAs in simple genomes that can be predicted computationally as a precursor to experimental study. Public access to our RNA gene predictions and an interface for user predictions is available via the web.

Computational Biology↗
PubMed2001

Differential distribution of simple sequence repeats in eukaryotic genome sequences.

Complete chromosome/genome sequences available from humans, Drosophila melanogaster, Caenorhabditis elegans, Arabidopsis thaliana, and Saccharomyces cerevisiae were analyzed for the occurrence of mono-, di-, tri-, and tetranucleotide repeats. In all of the genomes studied, dinucleotide repeat stretches tended to be longer than other repeats. Additionally, tetranucleotide repeats in humans and trinucleotide repeats in Drosophila also seemed to be longer. Although the trends for different repeats are similar between different chromosomes within a genome, the density of repeats may vary between different chromosomes of the same species. The abundance or rarity of various di- and trinucleotide repeats in different genomes cannot be explained by nucleotide composition of a sequence or potential of repeated motifs to form alternative DNA structures. This suggests that in addition to nucleotide composition of repeat motifs, characteristic DNA replication/repair/recombination machinery might play an important role in the genesis of repeats. Moreover, analysis of complete genome coding DNA sequences of Drosophila, C. elegans, and yeast indicated that expansions of codon repeats corresponding to small hydrophilic amino acids are tolerated more, while strong selection pressures probably eliminate codon repeats encoding hydrophobic and basic amino acids. The locations and sequences of all of the repeat loci detected in genome sequences and coding DNA sequences are available at http://www.ncl-india.org/ssr and could be useful for further studies.

Animals↗
PubMed1995

DNA repair mutants of Rhodobacter sphaeroides.

The genome of the photosynthetic eubacterium Rhodobacter sphaeroides 2.4.1 comprises two chromosomes and five endogenous plasmids and has a 65% G+C base composition. Because of these characteristics of genome architecture, as well as the physiological advantages that allow this organism to live in sunlight when in an anaerobic environment, the sensitivity of R. sphaeroides to UV radiation was compared with that of the more extensively studied bacterium Escherichia coli. R. sphaeroides was found to be more resistant, being killed at about 60% of the rate of E. coli. To begin to analyze the basis for this increased resistance, a derivative of R. sphaeroides, strain 2.4.1 delta S, which lacks the 42-kb plasmid, was mutagenized with a derivative of Tn5, and the transposon insertion mutants were screened for increased UV sensitivity (UVs). Eight UVs strains were isolated, and the insertion sites were determined by contour-clamped homogeneous electric field pulsed-field gel electrophoresis. These mapped to at least five different locations in chromosome I. Preliminary analysis suggested that these mutants were deficient in the repair of DNA damage. This was confirmed for three loci by DNA sequence analysis, which showed the insertions to be within genes homologous to uvrA, uvrB, and uvrC, the subunits of the nuclease responsible for excising UV damage.

Amino Acid Sequence↗