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At least 1,045 records · Page 58Linked to original sources
PubMed2003

Helicobacter pylori tissue tropism: mouse-colonizing strains can target different gastric niches.

Studies with the mouse-adapted Helicobacter pylori strain SS1 had supported an idea that infections by this pathogen start in the gastric antrum and spread to the corpus after extensive mucosal damage. This paper shows that the unrelated strain X47 colonizes the corpus preferentially. Differences between strains in preferred gastric region were detected by co-inoculating mice with a mixture of SS1 and X47, and genotyping H. pylori recovered after 2-8 weeks of infection by vacA s allele PCR and RAPD fingerprinting. Mixed infections were found in each of 59 co-inoculated young C57BL/6J mice. On average, however, SS1 was fourfold more abundant than X47 in the antrum and X47 was threefold more abundant than SS1 in the corpus. Similar results were obtained in mice inoculated first with one strain and then the other strain 2 weeks later. SS1 was even more abundant in the antrum of elderly (>1 year old) mice (97 % of isolates). Qualitatively similar SS1 and X47 tissue distributions were seen using unrelated mouse lines (AKR/J, A/J, DBA/2J, BALB/cJ, LG/J, SM/J), but with significantly different SS1 : X47 ratios in some cases. These results suggest the existence of at least two distinct gastric niches whose characteristics may be affected by host genotype and age (physiology), and indicate that strains differ in how effectively they colonize each niche. Differences among gastric regions and the mixed infections that these allow may contribute to H. pylori diversity and genome evolution.

Aging↗
PubMed2025

Transcriptome-wide analysis reveals sequence selection to avoid mRNA aggregation in E. coli.

The stability of RNA base pairing and its limited four-letter code create an intrinsic potential for promiscuous RNA-RNA interactions. In vitro, such interactions drive RNA to self-assemble into aggregates. This raises a fundamental unanswered question: within a confined cellular volume at physiological mRNA abundances, how much aggregation would arise from sequence-encoded chemistry alone? Here, we establish this baseline with large-scale kinetic simulations of the E. coli transcriptome. Our simulations reveal that sequence-encoded base-pairing energetics is sufficient to generate a dynamic network of large aggregates, organized by long, multivalent mRNA hubs. Strikingly, evolutionary analysis shows that native E. coli sequences exhibit clear signatures of selection to counteract this propensity: they fold more stably, minimize unstructured regions, and form weaker intermolecular contacts than dinucleotide-preserving controls. These findings demonstrate that maintaining transcriptome solubility has been a significant, previously unrecognized constraint shaping genome evolution, and provide a new lens to interpret cellular RNA management.

Biological Sciences (Biophysics and Computational ↗
PubMed2026

MRE11 suppresses germline mutagenesis at meiotic double-strand breaks in mice.

SPO11 forms hundreds of double-strand breaks (DSBs) to initiate meiotic recombination that is normally error-free. However, SPO11 activity can be mutagenic when one chromatid incurs closely spaced DSBs (double cuts), especially when DSBs are dysregulated by loss of the ATM kinase. De novo indels and structural variants can arise via end joining at double cuts within a single hotspot (microdeletions) or at adjacent hotspots separated by at least 30 kb, as we now show, sometimes accompanied by ectopic insertions of double-cut fragments. Here, we investigate how meiotic DSB end processing influences end joining. In MRE11-deficient mouse spermatocytes, which do not resect their DSBs, deletions at double cuts occur readily, with end-joining breakpoint profiles closely matching SPO11 DSB profiles. Microdeletions suggest that two DSBs can be as close as ∼21 bp. The tyrosyl-DNA phosphodiesterase TDP2 contributes to both deletion formation and ectopic insertion of double-cut fragments, presumably by removing SPO11 from DNA ends prior to joining. Finally, observations suggest a cooperative role for MRE11 and ATM in locally regulating DSB distributions. Our findings provide insight into the mechanism of de novo mutation origin, emphasizing the role of meiotic DSBs in shaping genome evolution.

Animals↗
PubMed2003

The origin of human chromosome 1 and its homologs in placental mammals.

Developing ordered gene maps from multiple mammalian species coupled with chromosome-painting data provide a powerful resource for resolving the evolutionary history of chromosomes and whole genomes. In this work, we recapitulate the evolutionary history of human chromosome 1 and its homologs in placental mammals, putatively the largest physical unit in the ancestral placental genome. Precise definition of translocation exchange breakpoints in human, carnivore, cetartiodactyl, and rodent-ordered gene maps demonstrate that chromosome breakpoints, previously considered as equivalent, actually represent distinct chromosome positions and exchange events. Multidirectional chromosome painting, using probes from homologs to chromosome 1 in seven mammal species from six orders of placental mammals, confirm the gene-mapping results and indicate that the multiple human chromosome 1 homologs in these species are derived from independent fissions of a single ancestral chromosome. Chromosome painting using human chromosome 1 probes identifies a single human chromosome 1 homolog in phylogenetically distant taxa, the two-toed sloth, cetaceans, and higher primates. The diverse phylogenetic occurrence of a single Hsa1 synteny among the major clades of placental mammals suggests that human chromosome 1 represents an intact ancestral chromosome, which was variously fissioned in the majority of placental species. We find that the number of human chromosome 1 fissions in a specific lineage reflects its general rate of genomic evolution. Further, historic chromosome exchange appears to have been disproportionately clustered in two breakpoint hotspots on the long arm.

Animals↗
PubMed2001

Partitioning of tissue expression accompanies multiple duplications of the Na+/K+ ATPase alpha subunit gene.

Vertebrate genomes contain multiple copies of related genes that arose through gene duplication. In the past it has been proposed that these duplicated genes were retained because of acquisition of novel beneficial functions. A more recent model, the duplication-degeneration-complementation hypothesis (DDC), posits that the functions of a single gene may become separately allocated among the duplicated genes, rendering both duplicates essential. Thus far, empirical evidence for this model has been limited to the engrailed and sox family of developmental regulators, and it has been unclear whether it may also apply to ubiquitously expressed genes with essential functions for cell survival. Here we describe the cloning of three zebrafish alpha subunits of the Na(+),K(+)-ATPase and a comprehensive evolutionary analysis of this gene family. The predicted amino acid sequences are extremely well conserved among vertebrates. The evolutionary relationships and the map positions of these genes and of other alpha-like sequences indicate that both tandem and ploidy duplications contributed to the expansion of this gene family in the teleost lineage. The duplications are accompanied by acquisition of clear functional specialization, consistent with the DDC model of genome evolution.

Amino Acid Sequence↗
PubMed2002

Athila4 of Arabidopsis and Calypso of soybean define a lineage of endogenous plant retroviruses.

The Athila retroelements of Arabidopsis thaliana encode a putative envelope gene, suggesting that they are infectious retroviruses. Because most insertions are highly degenerate, we undertook a comprehensive analysis of the A. thaliana genome sequence to discern their conserved features. One family (Athila4) was identified whose members are largely intact and share >94% nucleotide identity. As a basis for comparison, related elements (the Calypso elements) were characterized from soybean. Consensus Calypso and Athila4 elements are 12-14 kb in length and have long terminal repeats of 1.3-1.8 kb. Gag and Pol are encoded on a single open reading frame (ORF) of 1801 (Calypso) and 1911 (Athila4) amino acids. Following the Gag-Pol ORF are noncoding regions of ~0.7 and 2 kb, which, respectively, flank the env-like gene. The env-like ORF begins with a putative splice acceptor site and encodes a protein with a predicted central transmembrane domain, similar to retroviral env genes. RNA of Athila elements was detected in an A. thaliana strain with decreased DNA methylation (ddm1). Additionally, a PCR survey identified related reverse transcriptases in diverse angiosperm genomes. Their ubiquitous nature and the potential for horizontal transfer by infection implicates these endogenous retroviruses as important vehicles for plant genome evolution.

Amino Acid Sequence↗
PubMed2003

Genomic DNA insertions and deletions occur frequently between humans and nonhuman primates.

Comparative DNA sequence studies between humans and nonhuman primates will be important for understanding the genetic basis of the phenotypic differences between these species. Here we compare approximately 27 Mb of human chromosome 21 with chimpanzee DNA sequences identifying 57 genomic rearrangements (deletions and insertions ranging in size from 0.2 to 8.0 kb) between the two species. These rearrangements are distributed along the entire length of chromosome 21, with approximately 35% found in genomic intervals encoding genes (genic intervals), and have occurred in the genomes of both humans and chimpanzees. Comparison of approximately 9 Mb of human chromosome 21 with orangutan, rhesus macaque, and woolly monkey DNA sequences identified a combined total of 114 genomic rearrangements between humans and nonhuman primates. Analysis of these rearrangements revealed that they are randomly distributed with respect to genic and nongenic intervals and identified one deletion that has likely resulted in the inactivation of a gene (beta1,3-galactosyltransferase) in the woolly monkey. Our data show that genomic rearrangements have occurred frequently during primate genome evolution and significantly contribute to the DNA differences between these species. These DNA rearrangements are commonly found in genic intervals, and thus provide natural starting points for focused investigations of qualitative and quantitative gene expression differences between humans and other primates.

Animals↗
PubMed2003

Pericentromeric duplications in the laboratory mouse.

Duplications have long been postulated to be an important mechanism by which genomes evolve. Interspecies genomic comparisons are one method by which the origin and molecular mechanism of duplications can be inferred. By comparative mapping in human, mouse, and rat, we previously found evidence for a recent chromosome-fission event that occurred in the mouse lineage. Cytogenetic mapping revealed that the genomic segments flanking the fission site appeared to be duplicated, with copies residing near the centromere of multiple mouse chromosomes. Here we report the mapping and sequencing of the regions of mouse chromosomes 5 and 6 involved in this chromosome-fission event as well as the results of comparative sequence analysis with the orthologous human and rat genomic regions. Our data indicate that the duplications associated with mouse chromosomes 5 and 6 are recent and that the resulting duplicated segments share significant sequence similarity with a series of regions near the centromeres of the mouse chromosomes previously identified by cytogenetic mapping. We also identified pericentromeric duplicated segments shared between mouse chromosomes 5 and 1. Finally, novel mouse satellite sequences as well as putative chimeric transcripts were found to be associated with the duplicated segments. Together, these findings demonstrate that pericentromeric duplications are not restricted to primates and may be a common mechanism for genome evolution in mammals.

Animals↗
PubMed1999

Identification of three novel Ca(2+) channel gamma subunit genes reveals molecular diversification by tandem and chromosome duplication.

Gene duplication is believed to be an important evolutionary mechanism for generating functional diversity within genomes. The accumulated products of ancient duplication events can be readily observed among the genes encoding voltage-dependent Ca(2+) ion channels. Ten paralogous genes have been identified that encode isoforms of the alpha(1) subunit, four that encode beta subunits, and three that encode alpha(2)delta subunits. Until recently, only a single gene encoding a muscle-specific isoform of the Ca(2+) channel gamma subunit (CACNG1) was known. Expression of a distantly related gene in the brain was subsequently demonstrated upon isolation of the Cacng2 gene, which is mutated in the mouse neurological mutant stargazer (stg). In this study, we sought to identify additional genes that encoded gamma subunits. Because gene duplication often generates paralogs that remain in close syntenic proximity (tandem duplication) or are copied onto related daughter chromosomes (chromosome or whole-genome duplication), we hypothesized that the known positions of CACNG1 and CACNG2 could be used to predict the likely locations of additional gamma subunit genes. Low-stringency genomic sequence analysis of targeted regions led to the identification of three novel Ca(2+) channel gamma subunit genes, CACNG3, CACNG4, and CACNG5, on chromosomes 16 and 17. These results demonstrate the value of genome evolution models for the identification of distantly related members of gene families.

Amino Acid Sequence↗
PubMed2006

Informational structure of two closely related eukaryotic genomes.

Attempts to identify a species on the basis of its DNA sequence on purely statistical grounds have been formulated for more than a decade. The most prominent of such genome signatures relies on neighborhood correlations (i.e., dinucleotide frequencies) and, consequently, attributes species identification to mechanisms operating on the dinucleotide level (e.g., neighbor-dependent mutations). For the examples of Mus musculus and Rattus norvegicus we analyze short- and intermediate-range statistical correlations in DNA sequences. These correlation profiles are computed for all chromosomes of the two species. We find that with increasing range of correlations the capacity to distinguish between the species on the basis of this correlation profile is getting better and requires ever shorter sequence segments for obtaining a full species separation. This finding suggests that distinctive traits within the sequence are situated beyond the level of few nucleotides. The large-scale statistical patterning of DNA sequences on which such genome signatures are based is thus substantially determined by mobile elements (e.g., transposons and retrotransposons). The study and interspecies comparison of such correlation profiles can, therefore, reveal features of retrotransposition, segmental duplications, and other processes of genome evolution.

Animals↗
PubMed2005

SINE insertion polymorphism on the X chromosome differentiates Anopheles gambiae molecular forms.

Polymorphic SINE insertions can be useful markers for assessing population structure and differentiation. Maque is a family of SINE elements which, based on bioinformatic analysis, was suggested to have been active recently in Anopheles gambiae, the major vector of malaria. Here, we report the development of polymorphic Maque insertions as population genetic markers in A. gambiae, and the use of these markers to better characterize divergence on the X chromosome between A. gambiae M and S molecular forms in populations from Burkina Faso and Mali. Our data are consistent with the recent activity of Maque. Phylogenetic analysis suggests that at least two recently active lineages may have a role in mediating genome evolution. We found differences in element insertion frequency and sequence between the M and S populations analysed. Significant differentiation was observed between these two groups across a 6 Mb region at the proximal (centromeric) end of the X chromosome. Locus-specific F(ST) values ranged from 0.14 to 1.00 in this region, yet were not significantly different from zero in more distal locations on the X chromosome; the trend was consistent in populations from both geographical locales suggesting that differentiation is not due to local adaptation. Strong differentiation between M and S at the proximal end of the X chromosome, but not outside this region, suggests the action of selection counteracting limited gene flow between these taxa and supports their characterization as incipient species.

Animals↗
PubMedDate not supplied

Molecular characterization of nuclear small subunit (18S)-rDNA pseudogenes in a symbiotic dinoflagellate (Symbiodinium, Dinophyta).

For the dinoflagellates, an important group of single-cell protists, some nuclear rDNA phylogenetic studies have reported the discovery of rDNA pseudogenes. However, it is unknown if these aberrant molecules are confined to free-living taxa or occur in other members of the group. We have cultured a strain of symbiotic dinoflagellate, belonging to the genus Symbiodinium, which produces three distinct amplicons following PCR for nuclear small subunit (18S) rDNA genes. These amplicons contribute to a unique restriction fragment length polymorphism pattern diagnostic for this particular strain. Sequence analyses revealed that the largest amplicon was the expected region of 18S-rDNA, while the two smaller amplicons are Symbiodinium nuclear 18S-rDNA genes that contain single long tracts of nucleotide deletions. Reverse transcription (RT)-PCR experiments did not detect RNA transcripts of these latter genes, suggesting that these molecules represent the first report of nuclear 18S-rDNA pseudogenes from the genome of Symbiodinium. As in the free-living dinoflagellates, nuclear rDNA pseudogenes are effective indicators of unique Symbiodinium strains. Furthermore, the evolutionary pattern of dinoflagellate nuclear rDNA pseudogenes appears to be unique among organisms studied to date, and future studies of these unusual molecules will provide insight on the cellular biology and genomic evolution of these protists.

Animals↗
PubMed2002

Bacterial group II introns in a deep-sea hydrothermal vent environment.

Group II introns are catalytic RNAs and mobile retrotransposable elements known to be present in the genomes of some nonmarine bacteria and eukaryotic organelles. Here we report the discovery of group II introns in a bacterial mat sample collected from a deep-sea hydrothermal vent near 9 degrees N on the East Pacific Rise. One of the introns was shown to self-splice in vitro. This is the first example of marine bacterial introns from molecular population structure studies of microorganisms that live in the proximity of hydrothermal vents. These types of mobile genetic elements may prove useful in improving our understanding of bacterial genome evolution and may serve as valuable markers in comparative studies of bacterial communities.

Amino Acid Sequence↗
PubMed2003

Extent of genetic lesions of the arginine and pyrimidine biosynthetic pathways in Lactobacillus plantarum, L. paraplantarum, L. pentosus, and L. casei: prevalence of CO(2)-dependent auxotrophs and characterization of deficient arg genes in L. plantarum.

Lactic acid bacteria require rich media since, due to mutations in their biosynthetic genes, they are unable to synthesize numerous amino acids and nucleobases. Arginine biosynthesis and pyrimidine biosynthesis have a common intermediate, carbamoyl phosphate (CP), whose synthesis requires CO(2). We investigated the extent of genetic lesions in both the arginine biosynthesis and pyrimidine biosynthesis pathways in a collection of lactobacilli, including 150 strains of Lactobacillus plantarum, 32 strains of L. pentosus, 15 strains of L. paraplantarum, and 10 strains of L. casei. The distribution of prototroph and auxotroph phenotypes varied between species. All L. casei strains, no L. paraplantarum strains, two L. pentosus strains, and seven L. plantarum strains required arginine for growth. Arginine auxotrophs were more frequently found in L. plantarum isolated from milk products than in L. plantarum isolated from fermented plant products or humans; association with dairy products might favor arginine auxotrophy. In L. plantarum the argCJBDF genes were functional in most strains, and when they were inactive, only one gene was mutated in more than one-half of the arginine auxotrophs. Random mutation may have generated these auxotrophs since different arg genes were inactivated (there were single point mutations in three auxotrophs and nonrevertible genetic lesions in four auxotrophs). These data support the hypothesis that lactic acid bacteria evolve by progressively loosing unnecessary genes upon adaptation to specific habitats, with genome evolution towards cumulative DNA degeneration. Although auxotrophy for only uracil was found in one L. pentosus strain, a high CO(2) requirement (HCR) for arginine and pyrimidine was common; it was found in 74 of 207 Lactobacillus strains tested. These HCR auxotrophs may have had their CP cellular pool-related genes altered or deregulated.

Arginine↗
PubMed2006

Evolutionary origins of the eukaryotic shikimate pathway: gene fusions, horizontal gene transfer, and endosymbiotic replacements.

Currently the shikimate pathway is reported as a metabolic feature of prokaryotes, ascomycete fungi, apicomplexans, and plants. The plant shikimate pathway enzymes have similarities to prokaryote homologues and are largely active in chloroplasts, suggesting ancestry from the plastid progenitor genome. Toxoplasma gondii, which also possesses an alga-derived plastid organelle, encodes a shikimate pathway with similarities to ascomycete genes, including a five-enzyme pentafunctional arom. These data suggests that the shikimate pathway and the pentafunctional arom either had an ancient origin in the eukaryotes or was conveyed by eukaryote-to-eukaryote horizontal gene transfer (HGT). We expand sampling and analyses of the shikimate pathway genes to include the oomycetes, ciliates, diatoms, basidiomycetes, zygomycetes, and the green and red algae. Sequencing of cDNA from Tetrahymena thermophila confirmed the presence of a pentafused arom, as in fungi and T. gondii. Phylogenies and taxon distribution suggest that the arom gene fusion event may be an ancient eukaryotic innovation. Conversely, the Plantae lineage (represented here by both Viridaeplantae and the red algae) acquired different prokaryotic genes for all seven steps of the shikimate pathway. Two of the phylogenies suggest a derivation of the Plantae genes from the cyanobacterial plastid progenitor genome, but if the full Plantae pathway was originally of cyanobacterial origin, then the five other shikimate pathway genes were obtained from a minimum of two other eubacterial genomes. Thus, the phylogenies demonstrate both separate HGTs and shared derived HGTs within the Plantae clade either by primary HGT transfer or secondarily via the plastid progenitor genome. The shared derived characters support the holophyly of the Plantae lineage and a single ancestral primary plastid endosymbiosis. Our analyses also pinpoints a minimum of 50 gene/domain loss events, demonstrating that loss and replacement events have been an important process in eukaryote genome evolution.

Alcohol Oxidoreductases↗
PubMed2006

Plasmid diversity in neisseriae.

Horizontal gene transfer constitutes an important force in prokaryotic genome evolution, and it is well-known that plasmids are vehicles for DNA transfer. Chromosomal DNA is frequently exchanged between pathogenic and commensal neisseriae, but relatively little is known about plasmid diversity and prevalence among these nasopharyngeal inhabitants. We investigated the plasmid contents of 18 Neisseria lactamica isolates and 20 nasopharyngeal Neisseria meningitidis isolates. Of 18 N. lactamica strains, 9 harbored one or more plasmids, whereas only one N. meningitidis isolate contained a plasmid. Twelve plasmids were completely sequenced, while five plasmid sequences from the public databases were also included in the analyses. On the basis of nucleic acid sequences, mobilization, and replicase protein alignments, we distinguish six different plasmid groups (I to VI). Three plasmids from N. lactamica appeared to be highly similar on the nucleotide level to the meningococcal plasmids pJS-A (>99%) and pJS-B (>75%). The genetic organizations of two plasmids show a striking resemblance with that of the recently identified meningococcal disease-associated (MDA) phage, while four putative proteins encoded by these plasmids show 25% to 39% protein identity to those encoded by the MDA phage. The putative promoter of the gene encoding the replicase on these plasmids contains a polycytidine tract, suggesting that replication is subjected to phase variation. In conclusion, extensive plasmid diversity is encountered among commensal neisseriae. Members of three plasmid groups are found in both pathogenic and commensal neisseriae, indicating plasmid exchange between these species. Resemblance between plasmids and MDA phage may be indicative of dissemination of phage-related sequences among pathogenic and commensal neisseriae.

Bacterial Proteins↗
PubMed2006

Identification of differentially expressed genes in virulent and nonvirulent Entamoeba species: potential implications for amebic pathogenesis.

Entamoeba histolytica is a protozoan parasite that causes colitis and liver abscesses. Several Entamoeba species and strains with differing levels of virulence have been identified. E. histolytica HM-1:IMSS is a virulent strain, E. histolytica Rahman is a nonvirulent strain, and Entamoeba dispar is a nonvirulent species. We used an E. histolytica DNA microarray consisting of 2,110 genes to assess the transcriptional differences between these species/strains with the goal of identifying genes whose expression correlated with a virulence phenotype. We found 415 genes expressed at lower levels in E. dispar and 32 genes with lower expression in E. histolytica Rahman than in E. histolytica HM-1:IMSS. Overall, 29 genes had decreased expression in both the nonvirulent species/strains than the virulent E. histolytica HM-1:IMSS. Interestingly, a number of genes with potential roles in stress response and virulence had decreased expression in either one or both nonvirulent Entamoeba species/strains. These included genes encoding Fe hydrogenase (9.m00419), peroxiredoxin (176.m00112), type A flavoprotein (6.m00467), lysozyme (6.m00454), sphingomyelinase C (29.m00231), and a hypothetical protein with homology to both a Plasmodium sporozoite threonine-asparagine-rich protein (STARP) and a streptococcal hemagglutinin (238.m00054). The function of these genes in Entamoeba and their specific roles in parasite virulence need to be determined. We also found that a number of the non-long-terminal-repeat retrotransposons (EhLINEs and EhSINEs), which have been shown to modulate gene expression and genomic evolution, had lower expression in the nonvirulent species/strains than in E. histolytica HM-1:IMSS. Our results, identifying expression profiles and patterns indicative of a virulence phenotype, may be useful in characterizing the transcriptional framework of virulence.

Animals↗
PubMed1992

A temperature-regulated, retrotransposon-like element from Candida albicans.

A repetitive element was isolated from the genome of Candida albicans. This repetitive element, which we designated alpha, was localized to a 500-bp fragment of genomic DNA. The alpha element was dispersed in the genome and varied in copy number and genomic location in the strains examined. Analyses of various loci containing the alpha element identified a locus containing a composite element. This composite element consisted of two direct repeats of the alpha element separated by approximately 5.5 kb of DNA, a structural arrangement similar to that of retrovirus-like transposable elements. The flanking alpha elements of the composite structure were 388 bp in length and were identical in sequence. They were bounded by the nucleotides 5'-TG. ... CA-3', which were part of a delimiting inverted repeat, a feature conserved in the long terminal repeats of retroviruses and retrovirus-like elements. As in retrovirus-like elements, the entire composite element, including the alpha elements, was transcribed into an approximately unit-length mRNA. The expression of this transcript was greatly increased when cells were grown at 25 versus 37 degrees C. As has been found in many retrotransposons, the composite element was flanked by a 5-bp duplication and varied in both copy number and genomic location in various strains. We conclude that the composite element is a retrotransposon-like element, and we have designated this element Tca1. We suggest that Tca1 may be relevant to the genomic evolution of C. albicans and the pathogenic potential of the organism.

Base Sequence↗