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At least 955 records · Page 53Linked to original sources
PubMed1987

Mouse protamine 2 is synthesized as a precursor whereas mouse protamine 1 is not.

The nuclei of mouse spermatozoa contain two protamine variants, mouse protamine 1 (mP1) and mouse protamine 2 (mP2). The amino acid sequence predicted from mP1 cDNAs demonstrates that mP1 is a 50-amino-acid protein with strong homology to other mammalian P1 protamines. Nucleotide sequence analysis of independently isolated, overlapping cDNA clones indicated that mP2 is initially synthesized as a precursor protein which is subsequently processed into the spermatozoan form of mP2. The existence of the mP2 precursor was confirmed by amino acid composition and sequence analysis of the largest of a set of four basic proteins isolated from late-step spermatids whose synthesis is coincident with that of mP1. The sequence of the first 10 amino acids of this protein, mP2 precursor 1, exactly matches that predicted from the nucleotide sequence of cDNA and genomic mP2 clones. The amino acid composition of isolated mP2 precursor 1 very closely matches that predicted from the mP2 cDNA nucleotide sequence. Sequence analysis of the amino terminus of isolated mature mP2 identified the final processing point within the mP2 precursor. These studies demonstrated that mP2 is synthesized as a precursor containing 106 amino acids which is processed into the mature, 63-amino-acid form found in spermatozoa.

Amino Acid Sequence↗
PubMed2024

A functional genomic framework to elucidate novel causal metabolic dysfunction-associated fatty liver disease genes.

BACKGROUND AND AIMS: Metabolic dysfunction-associated fatty liver disease (MASLD) is the most prevalent chronic liver pathology in western countries, with serious public health consequences. Efforts to identify causal genes for MASLD have been hampered by the relative paucity of human data from gold standard magnetic resonance quantification of hepatic fat. To overcome insufficient sample size, genome-wide association studies using MASLD surrogate phenotypes have been used, but only a small number of loci have been identified to date. In this study, we combined genome-wide association studies of MASLD composite surrogate phenotypes with genetic colocalization studies followed by functional in vitro screens to identify bona fide causal genes for MASLD. APPROACH AND RESULTS: We used the UK Biobank to explore the associations of our novel MASLD score, and genetic colocalization to prioritize putative causal genes for in vitro validation. We created a functional genomic framework to study MASLD genes in vitro using CRISPRi. Our data identify VKORC1 , TNKS , LYPLAL1 , and GPAM as regulators of lipid accumulation in hepatocytes and suggest the involvement of VKORC1 in the lipid storage related to the development of MASLD. CONCLUSIONS: Complementary genetic and genomic approaches are useful for the identification of MASLD genes. Our data supports VKORC1 as a bona fide MASLD gene. We have established a functional genomic framework to study at scale putative novel MASLD genes from human genetic association studies.

Humans↗
PubMed1999

Functional classes in the three domains of life.

The evolutionary divergence among the three major domains of life can now be addressed through the first set of complete genomes from representative species. These model species from the three domains of life, Haemophilus influenzae for Bacteria, Saccharomyces cerevisiae for Eukarya, and Methanococcus jannaschii for Archaea, provide the basis for a universal functional classification and analysis. We have chosen 13 functional classes and three superclasses (ENERGY, COMMUNICATION and INFORMATION) as global descriptors of protein function. Compositional comparison of the three complete genomes reveals that functional classes are ubiquitous yet diverse in the three domains of life. Proteins related with ENERGY processes are generally represented in all three domains, while those related with COMMUNICATION represent the most distinctive functional feature of each single domain. Finally, functions related with INFORMATION processing (translation, transcription, and replication) show a complex behaviour. In Archaea, proteins in this superclass are related with proteins in either Eukarya or Bacteria, as recognized previously. The distribution of functional classes in the three domains accurately reflects the principal characteristics of cellular life forms.

Archaeal Proteins↗
PubMed2002

Comparative genomic analysis of the MHC: the evolution of class I duplication blocks, diversity and complexity from shark to man.

The major histocompatibility complex (MHC) genomic region is composed of a group of linked genes involved functionally with the adaptive and innate immune systems. The class I and class II genes are intrinsic features of the MHC and have been found in all the jawed vertebrates studied so far. The MHC genomic regions of the human and the chicken (B locus) have been fully sequenced and mapped, and the mouse MHC sequence is almost finished. Information on the MHC genomic structures (size, complexity, genic and intergenic composition and organization, gene order and number) of other vertebrates is largely limited or nonexistent. Therefore, we are mapping, sequencing and analyzing the MHC genomic regions of different human haplotypes and at least eight nonhuman species. Here, we review our progress with these sequences and compare the human MHC structure with that of the nonhuman primates (chimpanzee and rhesus macaque), other mammals (pigs, mice and rats) and nonmammalian vertebrates such as birds (chicken and quail), bony fish (medaka, pufferfish and zebrafish) and cartilaginous fish (nurse shark). This comparison reveals a complex MHC structure for mammals and a relatively simpler design for nonmammalian animals with a hypothetical prototypic structure for the shark. In the mammalian MHC, there are two to five different class I duplication blocks embedded within a framework of conserved nonclass I and/or nonclass II genes. With a few exceptions, the class I framework genes are absent from the MHC of birds, bony fish and sharks. Comparative genomics of the MHC reveal a highly plastic region with major structural differences between the mammalian and nonmammalian vertebrates. Additional genomic data are needed on animals of the reptilia, crocodilia and marsupial classes to find the origins of the class I framework genes and examples of structures that may be intermediate between the simple and complex MHC organizations of birds and mammals, respectively.

Animals↗
PubMed2006

Trend of amino acid composition of proteins of different taxa.

Archaea, bacteria and eukaryotes represent the main kingdoms of life. Is there any trend for amino acid compositions of proteins found in full genomes of species of different kingdoms? What is the percentage of totally unstructured proteins in various proteomes? We obtained amino acid frequencies for different taxa using 195 known proteomes and all annotated sequences from the Swiss-Prot data base. Investigation of the two data bases (proteomes and Swiss-Prot) shows that the amino acid compositions of proteins differ substantially for different kingdoms of life, and this difference is larger between different proteomes than between different kingdoms of life. Our data demonstrate that there is a surprisingly small selection for the amino acid composition of proteins for higher organisms (eukaryotes) and their viruses in comparison with the "random" frequency following from a uniform usage of codons of the universal genetic code. On the contrary, lower organisms (bacteria and especially archaea) demonstrate an enhanced selection of amino acids. Moreover, according to our estimates, 12%, 3% and 2% of the proteins in eukaryotic, bacterial and archaean proteomes are totally disordered, and long (> 41 residues) disordered segments are found to occur in 16% of arhaean, 20% of eubacterial and 43% of eukaryotic proteins for 19 archaean, 159 bacterial and 17 eukaryotic proteomes, respectively. A correlation between amino acid compositions of proteins of various taxa, show that the highest correlation is observed between eukaryotes and their viruses (the correlation coefficient is 0.98), and bacteria and their viruses (the correlation coefficient is 0.96), while correlation between eukaryotes and archaea is 0.85 only.

Amino Acid Sequence↗
PubMed2006

Recovering motifs from biased genomes: application of signal correction.

A significant problem in biological motif analysis arises when the background symbol distribution is biased (e.g. high/low GC content in the case of DNA sequences). This can lead to overestimation of the amount of information encoded in a motif. A motif can be depicted as a signal using information theory (IT). We apply two concepts from IT, distortion and patterned interference (a type of noise), to model genomic and codon bias respectively. This modeling approach allows us to correct a raw signal to recover signals that are weakened by compositional bias. The corrected signal is more likely to be discriminated from a biased background by a macromolecule. We apply this correction technique to recover ribosome-binding site (RBS) signals from available sequenced and annotated prokaryotic genomes having diverse compositional biases. We observed that linear correction was sufficient for recovering signals even at the extremes of these biases. Further comparative genomics studies were made possible upon correction of these signals. We find that the average Euclidian distance between RBS signal frequency matrices of different genomes can be significantly reduced by using the correction technique. Within this reduced average distance, we can find examples of class-specific RBS signals. Our results have implications for motif-based prediction, particularly with regards to the estimation of reliable inter-genomic model parameters.

Archaea↗
PubMed1995

A recombinational event in the history of luteoviruses probably induced by base-pairing between the genomes of two distinct viruses.

Alignments of luteovirus readthrough protein amino acid sequences show they consist of two distinct regions, here named the N domain and the C domain. N domain sequences were classified, and comparison of this gene phylogeny to phylogenies of other luteovirus genes revealed an anomaly in the relationships between beet western yellows luteovirus, cucurbit aphidborne yellows luteovirus (CABYV), and pea enation mosaic RNA1 (PEMV1). Together with alignments of virion protein and readthrough protein amino acid sequences, these gene phylogenies indicate the anomaly to be the result of two recombinational events, probably between ancestors of CABYV and PEMV1 and leading to the transfer of RNA coding for the N domain to an ancestor of CABYV. Two likely recombination sites were identified from the alignments, one at the 5' end of the readthrough protein gene and the other at the 5' end of the sequence coding for the C domain. Alignments of the nucleotide sequences encompassing the probable recombination sites suggest that base-pairing between the genomes of the two ancestral luteoviruses, resulting from local sequence similarity at the 5' end of the readthrough protein gene, probably induced one of the interspecies recombinational events.

Amino Acid Sequence↗
PubMed2001

A molecular genome scan analysis to identify chromosomal regions influencing economic traits in the pig. II. Meat and muscle composition.

Molecular genetic markers can be used to identify chromosomal regions that contain quantitative trait loci (QTL) that control meat quality and muscle composition traits in farm animals. To study this in pigs, a resource family was generated from a cross between two Berkshire grand sires and nine Yorkshire grand dams. A total of 525 F2 progeny from 65 matings of F1 parents were produced. Phenotypic data on 28 meat quality traits (drip loss, water holding capacity, firmness, color, marbling, percentage cholesterol, ultimate pH, fiber type, and several sensory panel and cooking traits) were collected on the F2 animals. Animals were genotyped for 125 microsatellite markers covering the entire genome. Least squares regression interval mapping was used for QTL detection. Significance thresholds were determined by permutation tests. A total of 60 QTL were detected at the 5% chromosome level for meat quality traits, on Chrs 1, 2, 4, 5, 6, 7, 8, 10, 11, 12, 13, 14, 15, 17, 18, and X, of which 9 and 1 QTL were significant at the 5% and 1% genome-wise levels (on Chrs 1, 5, 12, 15, and 17), respectively.

Adipose Tissue↗
PubMed2002

Simplifying the mosaic description of DNA sequences.

By using the Jensen-Shannon divergence, genomic DNA can be divided into compositionally distinct domains through a standard recursive segmentation procedure. Each domain, while significantly different from its neighbors, may, however, share compositional similarity with one or more distant (non-neighboring) domains. We thus obtain a coarse-grained description of the given DNA string in terms of a smaller set of distinct domain labels. This yields a minimal domain description of a given DNA sequence, significantly reducing its organizational complexity. This procedure gives a new means of evaluating genomic complexity as one examines organisms ranging from bacteria to human. The mosaic organization of DNA sequences could have originated from the insertion of fragments of one genome (the parasite) inside another (the host), and we present numerical experiments that are suggestive of this scenario.

Journal Article↗
PubMed2005

Citreicella thiooxidans gen. nov., sp. nov., a novel lithoheterotrophic sulfur-oxidizing bacterium from the Black Sea.

Four strains of obligately heterotrophic bacteria isolated from the oxygen-sulfide interface of the Black Sea are characterized. The bacteria are aerobic, Gram-negative, with lemon-like, nonmotile cells. Bacteriochlorophyll a is not detected. They are mesophilic and neutrophilic with a temperature range of 8-35 degrees C (optimum 25) and pH range of 6.5-8.5 (optimum 7.8). Their growth is NaCl dependent within a range of 5 and 60 (optimum 20) g l(-1). They are able to oxidize thiosulfate, sulfide and elemental sulfur to sulfate and to use metabolic energy from these reactions (lithoheterotrophy). According to the level of DNA reassociation of more than 40%, all isolates represent a single generic group. The G+C content of the DNA was in the range of 67.5-69.2mol%. According to phylogenetic analysis, the new isolates form a separate branch in the alpha-3 subdivision of the Proteobacteria together with two undescribed marine bacterial strains. On the basis of phenotypical and genomic properties, the new isolates are described as a new genus and species Citreicella thiooxidans gen. nov., sp. nov. The type strain is CHLG 1T ( = DSM 10146, UNIQEM U 228).

Alphaproteobacteria↗
PubMed2003

Extracting phylogenetic information from whole-genome sequencing projects: the lactic acid bacteria as a test case.

The availability of an ever increasing number of complete genome sequences of diverse prokaryotic taxa has led to the introduction of novel approaches to infer phylogenetic relationships among bacteria. In the present study the sequences of the 16S rRNA gene and nine housekeeping genes were compared with the fraction of shared putative orthologous protein-encoding genes, conservation of gene order, dinucleotide relative abundance and codon usage among 11 genomes of species belonging to the lactic acid bacteria. In general there is a good correlation between the results obtained with various approaches, although it is clear that there is a stronger phylogenetic signal in some data sets than in others, and that different parameters have different taxonomic resolutions. It appears that trees based on different kinds of information derived from whole-genome sequencing projects do not provide much additional information about the phylogenetic relationships among bacterial taxa compared to more traditional alignment-based methods. Nevertheless, it is expected that the study of these novel forms of information will have its value in taxonomy, to determine which genes are shared, when genes or sets of genes were lost in evolutionary history, to detect the presence of horizontally transferred genes and/or confirm or enhance the phylogenetic signal derived from traditional methods. Although these conclusions are based on a relatively small data set, they are largely in agreement with other studies and it is anticipated that similar trends will be observed when comparing other genomes.

Bacterial Proteins↗
PubMed1998

Inferring the major genomic mode of dominance and overdominance.

The mode of within-locus gene action in most genomic regions is termed as the major genomic mode, i.e., it is the within-locus allelic effects in most regions of the genome. Determining whether dominance or overdominance is the major genomic mode is important for two long-standing evolutionary genetics issues: 1. How is the genetic variation in most genomic regions maintained? 2. What is the major mechanism for heterosis? Many efforts have been made, but almost all of them suffer some explanational difficulties. Here we propose an alternative inference approach. It is based on the existent theoretical results on the correlation of the recombination rate and the level of neutral variation in different genomic regions. Positive and negative correlation suggest dominance and overdominance, respectively, as the major genomic mode. Zero correlations imply either few selected sites or about equal composition and distribution of dominant and overdominant regions in the genome, depending on the data distribution. This approach not only avoids all the problems associated with earlier approaches, but it is also particularly useful in organisms where controlled breeding is difficult. Well-corroborated data in Drosophila and recently emerging data in mice and humans all suggest dominance as the major genomic mode.

Animals↗
PubMed1998

Identification of quantitative trait loci affecting carcass composition in swine: I. Fat deposition traits.

One of the major determining factors in the price of market hogs today is backfat depth. Therefore, identification of regions of the genome affecting this trait could be very useful to the swine industry. A large resource population (n = 540) was developed by backcrossing F1 Meishan-White composite females to either Meishan or White composite boars. A genomic scan was conducted by genotyping all animals with microsatellite markers spaced at approximately 20-cM intervals across the entire porcine genome. Breed of origin for all chromosomal segments was determined using multipoint linkage procedures, and a least squares regression analysis was conducted. Nominal P-values were converted to a genome-wide level of significance to adjust for the numerous tests conducted. Traits analyzed were backfat depths at the first rib (FRIB); 10th rib (10th); last rib (LRIB); last lumbar (LLUM) vertebra; the average of FRIB, LRIB, and LLUM (AVBF); and weight of leaf fat (LEAF). Significant quantitative trait loci (QTL) were detected on chromosomes 1, 7, and X. Suggestive evidence for QTL was present on chromosomes 5, 8, 9, 10, 13, and 14. Genotypic means for the loci detected indicated a predominantly additive mode of inheritance. Meishan alleles produced fatter pigs for all loci except those on chromosomes 7 and 10. Additional research should be conducted to refine the estimated position of each QTL and its effect and determine epistatic interactions. These loci should be evaluated in other germplasms to determine whether allelic variation at the QTL exists in other breeds.

Adipose Tissue↗
PubMed2006

Replication-associated strand asymmetries in vertebrate genomes and implications for replicon size, DNA replication origin, and termination.

Strand compositional asymmetry has been observed in prokaryotes and used in predicting prokaryotic DNA replication origins and termini. However, it was not found in eukaryotic genomes by the same methods. We propose that transcription-associated strand asymmetries mask the replication-associated ones. By analyzing the nucleotide composition of intergenic sequences larger than 50 kb by cumulative skew diagrams (CSD), we found replication-associated strand asymmetry in vertebrate genomes. Furthermore, we found that the most common replicon sizes in vertebrates are 50-100 kb, and show evidence that the replication origin and termination regions of vertebrate genomes range from a discrete site to a broad zone.

Animals↗
PubMed2004

DNA replication origins in the Schizosaccharomyces pombe genome.

Origins of DNA replication in Schizosaccharomyces pombe lack a specific consensus sequence analogous to the Saccharomyces cerevisiae autonomously replicating sequence (ARS) consensus, raising the question of how they are recognized by the replication machinery. Because all well characterized S. pombe origins are located in intergenic regions, we analyzed the sequence properties and biological activity of such regions. The AT content of intergenes is very high ( approximately 70%), and runs of A's or T's occur with a significantly greater frequency than expected. Additionally, the two DNA strands in intergenes display compositional asymmetry that strongly correlates with the direction of transcription of flanking genes. Importantly, the sequence properties of known S. pombe origins of DNA replication are similar to those of intergenes in general. In functional studies, we assayed the in vivo origin activity of 26 intergenes in a 68-kb region of S. pombe chromosome 2. We also assayed the origin activity of sets of randomly chosen intergenes with the same length or AT content. Our data demonstrate that at least half of intergenes have potential origin activity and that the relative ability of an intergene to function as an origin is governed primarily by AT content and length. We propose a stochastic model for initiation of DNA replication in the fission yeast. In this model, the number of AT tracts in a given sequence is the major determinant of its probability of binding SpORC and serving as a replication origin. A similar model may explain some features of origins of DNA replication in metazoans.

Base Composition↗
PubMed1999

Genome system architecture and natural genetic engineering in evolution.

Molecular genetics teaches three lessons relevant to the nature of genetic change during evolution: (1) Genomes are organized as hierarchies of composite systems (multidomain protein-coding sequences; functional loci made up of regulatory, coding, processing, and intervening sequences; and multilocus regulons and replicons) interconnected and organized into specific "system architectures" by repetitive DNA elements. (2) Genetic change often occurs via natural genetic engineering systems (cellular biochemical functions, such as recombination complexes, topoisomerases, and mobile elements, capable of altering DNA sequence information and joining together different genomic components). (3) The activity of natural genetic systems is regulated by cellular control circuits with respect to the timing, activity levels, and specificities of DNA rearrangements (e.g., adaptive mutation, Ty element mobility, and P factor insertions). These three lessons provide plausible molecular explanations for the episodic, multiple, nonrandom DNA rearrangements needed to account for the evolution of novel genomic system architectures and complex multilocus adaptations. This molecular genetic perspective places evolutionary change in the biologically responsive context of cellular biochemistry.

Adaptation, Biological↗
PubMed2004

Genome of staphylococcal phage K: a new lineage of Myoviridae infecting gram-positive bacteria with a low G+C content.

Phage K is a polyvalent phage of the Myoviridae family which is active against a wide range of staphylococci. Phage genome sequencing revealed a linear DNA genome of 127,395 bp, which carries 118 putative open reading frames. The genome is organized in a modular form, encoding modules for lysis, structural proteins, DNA replication, and transcription. Interestingly, the structural module shows high homology to the structural module from Listeria phage A511, suggesting intergenus horizontal transfer. In addition, phage K exhibits the potential to encode proteins necessary for its own replisome, including DNA ligase, primase, helicase, polymerase, RNase H, and DNA binding proteins. Phage K has a complete absence of GATC sites, making it insensitive to restriction enzymes which cleave this sequence. Three introns (lys-I1, pol-I2, and pol-I3) encoding putative endonucleases were located in the genome. Two of these (pol-I2 and pol-I3) were found to interrupt the DNA polymerase gene, while the other (lys-I1) interrupts the lysin gene. Two of the introns encode putative proteins with homology to HNH endonucleases, whereas the other encodes a 270-amino-acid protein which contains two zinc fingers (CX(2)CX(22)CX(2)C and CX(2)CX(23)CX(2)C). The availability of the genome of this highly virulent phage, which is active against infective staphylococci, should provide new insights into the biology and evolution of large broad-spectrum polyvalent phages.

Amino Acid Sequence↗
PubMed1991

Characteristic features of the sonicated DNA of Agama agama agama L. (Reptilia, Agamidae) on hydroxyapatite columns, using mouse DNA as a reference.

Hydroxyapatite column chromatography has been used to study some properties of the extensively sheared DNA of the Rainbow lizard, Agama agama agama. Reassociation studies show that the genome has a Cot1/2 of 370. Approximately 15% of the genome is highly repetitive in nature. This repetitive fraction is resolved into thermally stable and less stable fractions. The stable fraction has a base composition of 47% GC, higher than the 40.2% GC for the native DNA. This stable fraction is believed to be of recent origin. Chromatography of the total DNA of the lizard with linear gradients of phosphate buffer containing 1 M urea resolves it into two components which were shown by thermal fractionation, also in the presence of 1 M urea, to vary in base composition. This behaviour may be characteristic of reptilian genomes and may be used as a basis for studying the structural organisation of the reptilian genome.

Animals↗