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PubMed2025

Pathway-specific genomic alterations in pancreatic cancer across diverse cohorts.

BACKGROUND/OBJECTIVES: Pancreatic cancer (PC) is an aggressive malignancy with rising incidence and poor survival rates. While Hispanic/Latino (H/L) patients have a lower overall incidence compared to Non-Hispanic White (NHW) patients, they are diagnosed at younger ages, often present with more advanced disease, and experience worse survival outcomes. The molecular drivers underlying these disparities remain poorly understood. Key oncogenic pathways, including TP53, WNT, PI3K, TGF-Beta, and RTK/RAS, play crucial roles in tumor progression, therapy resistance, and response to targeted treatments. However, their ethnicity-specific alterations and prognostic implications in PC remain largely unexplored. This study aims to characterize pathway-specific mutations in PC among H/L and NHW patients, assess tumor mutation burden, and identify ethnicity-specific oncogenic drivers using publicly available datasets. The findings may provide critical insights to optimize precision medicine strategies and enhance targeted therapies for underrepresented populations. METHODS: A bioinformatics analysis was performed using publicly available PC datasets to evaluate mutation frequencies in genes associated with the TGF-Beta, RTK/RAS, WNT, PI3K, and TP53 pathways. The study included 4,248 patients, with 407 identified as H/L and 3,841 as NHW. Patients were stratified by ethnicity to assess differences in mutation prevalence. Chi-squared tests were conducted to compare mutation rates between groups, while Kaplan-Meier survival analysis was performed to evaluate overall survival differences based on pathway-specific alterations. RESULTS: Significant differences were observed in the TGF-Beta pathway between H/L and NHW patients. TGF-Beta mutations were less prevalent in H/L patients (18.4% vs. 24.4%, p = 8.6e-3). Additionally, genes related to the TGF-Beta pathway showed significant alterations, with SMAD2 (1.5% vs. 0.4%, p = 6.3e-3) and SMAD4 (15% vs. 19.9%, p = 0.02) exhibiting notable differences. Although RTK/RAS, WNT, PI3K, and TP53 pathway mutations were not statistically significant overall, borderline significance was observed in genes associated with these pathways, including ERBB4 (3.4% vs. 1.8%, p = 0.03), ALK (2.7% vs. 1.1%, p = 0.01), HRAS (1.2% vs. 0.1%, p = 1.3e-4), and RIT1 (0.7% vs. 0.1%, p = 0.03) in the RTK/RAS pathway, as well as CTNNB1 (2.9% vs. 1.3%, p = 0.01) in the WNT pathway. Survival analysis revealed no significant differences in overall survival among H/L patients. However, NHW patients with TP53 pathway alterations exhibited borderline significant differences in survival outcomes.

PI3K pathway↗

PubMed2025

Longitudinal Multi-Organ Transcriptomic Atlas of Salt-Induced Hypertension.

BACKGROUND: Salt-sensitive hypertension is a prevalent and clinically significant subtype of hypertension, where increased dietary salt intake elevates blood pressure and causes injury to multiple organ systems. Despite extensive research, dynamic molecular changes and conserved versus organ-specific transcriptional programs in hypertensive multi-organ damage remain poorly understood. Defining complex molecular pathways both in a temporal sequence and in an organ-specific manner is essential for developing targeted, precision therapies to mitigate hypertensive disease burden. METHODS: We generated a longitudinal multi-organ transcriptomic atlas of salt-sensitive hypertension using RNA sequencing of kidney cortex, kidney medulla, heart, and liver from Dahl salt-sensitive rats across four disease stages. A comprehensive bioinformatic analysis mapped dynamic transcriptional programs, evaluated 50 biological pathways, and defined upstream regulators. Histological and biochemical assays complemented transcriptomic analysis, while integration with human genome-wide association studies (GWAS) and compound-transcriptome analysis provided translational insights and identified candidate therapeutics. RESULTS: Salt-induced hypertension elicited both shared and tissue-specific transcriptional programs that evolved with disease progression. The kidney medulla showed robust early immune activation with metabolic suppression, while the cortex exhibited transient metabolic activation before declining and initiating immune activation. The liver and heart showed time-dependent metabolic and inflammatory remodeling. Cross-organ comparisons revealed a shared early proliferative response that converged on proinflammatory and fibrotic signatures. Upstream regulator analysis identified 79 time- and tissue-specific transcription factors associated with gene expression dynamics. GWAS integration analysis revealed endocrine signaling, ion transport, lipid metabolism, and detoxification as conserved pathways across species, underscoring the translational relevance of the model and study. Predictive compound-transcriptome analyses identified kinase inhibitors targeting phosphoinositide 3-kinase, mechanistic target of rapamycin and cyclin-dependent kinases as top candidates to counteract maladaptive transcriptional programs. CONCLUSIONS: This study defines temporal and tissue-specific transcriptomic remodeling in salt-sensitive hypertension and highlights the need for precision interventions to prevent progressive organ damage.

Journal Article↗

PubMed2005

Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA.

This paper shows that the small RNA MicA (previously SraD) is an antisense regulator of ompA in Escherichia coli. MicA accumulates upon entry into stationary phase and down-regulates the level of ompA mRNA. Regulation of ompA (outer membrane protein A), previously attributed to Hfq/mRNA binding, is lost upon deletion of the micA gene, whereas overexpression of MicA inhibits the synthesis of OmpA. In vitro, MicA binds to the ompA mRNA leader. Enzymatic and chemical probing was used to map the structures of MicA, the ompA mRNA leader, and the complex formed upon binding. MicA binding generates a footprint across the ompA Shine-Dalgarno sequence, consistent with a 12 + 4 base-pair interaction, which is additionally supported by the effect of mutations in vivo and by bioinformatics analysis of enterobacterial micA/ompA homolog sequences. MicA is conserved in many enterobacteria, as is its ompA target site. In vitro toeprinting confirmed that binding of MicA specifically interferes with ribosome binding. We propose that MicA, when present at high levels, blocks ribosome binding at the ompA translation start site, which-in line with previous work-secondarily facilitates RNase E cleavage and subsequent mRNA decay. MicA requires the presence of the Hfq protein, although the mechanistic basis for this remains unclear.

Bacterial Outer Membrane Proteins↗

PubMed2003

The secreted protein discovery initiative (SPDI), a large-scale effort to identify novel human secreted and transmembrane proteins: a bioinformatics assessment.

A large-scale effort, termed the Secreted Protein Discovery Initiative (SPDI), was undertaken to identify novel secreted and transmembrane proteins. In the first of several approaches, a biological signal sequence trap in yeast cells was utilized to identify cDNA clones encoding putative secreted proteins. A second strategy utilized various algorithms that recognize features such as the hydrophobic properties of signal sequences to identify putative proteins encoded by expressed sequence tags (ESTs) from human cDNA libraries. A third approach surveyed ESTs for protein sequence similarity to a set of known receptors and their ligands with the BLAST algorithm. Finally, both signal-sequence prediction algorithms and BLAST were used to identify single exons of potential genes from within human genomic sequence. The isolation of full-length cDNA clones for each of these candidate genes resulted in the identification of >1000 novel proteins. A total of 256 of these cDNAs are still novel, including variants and novel genes, per the most recent GenBank release version. The success of this large-scale effort was assessed by a bioinformatics analysis of the proteins through predictions of protein domains, subcellular localizations, and possible functional roles. The SPDI collection should facilitate efforts to better understand intercellular communication, may lead to new understandings of human diseases, and provides potential opportunities for the development of therapeutics.

Cell Adhesion Molecules, Neuronal↗

PubMed2004

High-throughput expression of C. elegans proteins.

Proteome-scale studies of protein three-dimensional structures should provide valuable information for both investigating basic biology and developing therapeutics. Critical for these endeavors is the expression of recombinant proteins. We selected Caenorhabditis elegans as our model organism in a structural proteomics initiative because of the high quality of its genome sequence and the availability of its ORFeome, protein-encoding open reading frames (ORFs), in a flexible recombinational cloning format. We developed a robotic pipeline for recombinant protein expression, applying the Gateway cloning/expression technology and utilizing a stepwise automation strategy on an integrated robotic platform. Using the pipeline, we have carried out heterologous protein expression experiments on 10,167 ORFs of C. elegans. With one expression vector and one Escherichia coli strain, protein expression was observed for 4854 ORFs, and 1536 were soluble. Bioinformatics analysis of the data indicates that protein hydrophobicity is a key determining factor for an ORF to yield a soluble expression product. This protein expression effort has investigated the largest number of genes in any organism to date. The pipeline described here is applicable to high-throughput expression of recombinant proteins for other species, both prokaryotic and eukaryotic, provided that ORFeome resources become available.

Animals↗

PubMed2004

High-content screening microscopy identifies novel proteins with a putative role in secretory membrane traffic.

Here we describe the establishment of microscope-based functional screening assays in intact cells that allow us to systematically identify new proteins involved in secretory membrane traffic, and proteins that can influence the integrity of the Golgi complex. We were able to identify 20 new proteins that affected either secretory transport, Golgi morphology, or both, when overexpressed in cells. Control experiments with human orthologs to yeast proteins with a role in membrane traffic, or already well characterized mammalian regulators of the secretory pathway, confirmed the specificity and significance of our results. Proteins localized to the Golgi complex or endoplasmic reticulum (ER) showed preferential interference in our assays. Bioinformatic analysis of the new proteins interfering with membrane traffic and/or Golgi integrity revealed broad functional variety, but demonstrated a bias towards proteins with predicted coiled-coil domains and repeat structures. Extending our approach to a much larger set of novel proteins in the future will be an important step toward a more comprehensive understanding of the molecular basis of the secretory pathway. It will also serve as an example for similar microscope-based screens addressing different biological questions.

Cell Membrane↗

PubMed2005

Gene-breaking: a new paradigm for human retrotransposon-mediated gene evolution.

The L1 retrotransposon is the most highly successful autonomous retrotransposon in mammals. This prolific genome parasite may on occasion benefit its host through genome rearrangements or adjustments of host gene expression. In examining possible effects of L1 elements on host gene expression, we investigated whether a full-length L1 element inserted in the antisense orientation into an intron of a cellular gene may actually split the gene's transcript into two smaller transcripts: (1) a transcript containing the upstream exons and terminating in the major antisense polyadenylation site (MAPS) of the L1, and (2) a transcript derived from the L1 antisense promoter (ASP) that includes the downstream exons of the gene. Bioinformatic analysis and experimental follow-up provide evidence for this L1 "gene-breaking" hypothesis. We identified three human genes apparently "broken" by L1 elements, as well as 12 more candidate genes. Most of the inserted L1 elements in our 15 candidate genes predate the human/chimp divergence. If indeed split, the transcripts of these genes may in at least one case encode potentially interacting proteins, and in another case may encode novel proteins. Gene-breaking represents a new mechanism through which L1 elements remodel mammalian genomes.

Animals↗

PubMed2006

MAIZEWALL. Database and developmental gene expression profiling of cell wall biosynthesis and assembly in maize.

An extensive search for maize (Zea mays) genes involved in cell wall biosynthesis and assembly has been performed and 735 sequences have been centralized in a database, MAIZEWALL (http://www.polebio.scsv.ups-tlse.fr/MAIZEWALL). MAIZEWALL contains a bioinformatic analysis for each entry and gene expression data that are accessible via a user-friendly interface. A maize cell wall macroarray composed of a gene-specific tag for each entry was also constructed to monitor global cell wall-related gene expression in different organs and during internode development. By using this macroarray, we identified sets of genes that exhibit organ and internode-stage preferential expression profiles. These data provide a comprehensive fingerprint of cell wall-related gene expression throughout the maize plant. Moreover, an in-depth examination of genes involved in lignin biosynthesis coupled to biochemical and cytological data from different organs and stages of internode development has also been undertaken. These results allow us to trace spatially and developmentally regulated, putative preferential routes of monolignol biosynthesis involving specific gene family members and suggest that, although all of the gene families of the currently accepted monolignol biosynthetic pathway are conserved in maize, there are subtle differences in family size and a high degree of complexity in spatial expression patterns. These differences are in keeping with the diversity of lignified cell types throughout the maize plant.

Cell Wall↗

PubMed2004

A systemic small RNA signaling system in plants.

Systemic translocation of RNA exerts non-cell-autonomous control over plant development and defense. Long-distance delivery of mRNA has been proven, but transport of small interfering RNA and microRNA remains to be demonstrated. Analyses performed on phloem sap collected from a range of plants identified populations of small RNA species. The dynamic nature of this population was reflected in its response to growth conditions and viral infection. The authenticity of these phloem small RNA molecules was confirmed by bioinformatic analysis; potential targets for a set of phloem small RNA species were identified. Heterografting studies, using spontaneously silencing coat protein (CP) plant lines, also established that transgene-derived siRNA move in the long-distance phloem and initiate CP gene silencing in the scion. Biochemical analysis of pumpkin (Cucurbita maxima) phloem sap led to the characterization of C. maxima Phloem SMALL RNA BINDING PROTEIN1 (CmPSRP1), a unique component of the protein machinery probably involved in small RNA trafficking. Equivalently sized small RNA binding proteins were detected in phloem sap from cucumber (Cucumis sativus) and lupin (Lupinus albus). PSRP1 binds selectively to 25-nucleotide single-stranded RNA species. Microinjection studies provided direct evidence that PSRP1 could mediate the cell-to-cell trafficking of 25-nucleotide single-stranded, but not double-stranded, RNA molecules. The potential role played by PSRP1 in long-distance transmission of silencing signals is discussed with respect to the pathways and mechanisms used by plants to exert systemic control over developmental and physiological processes.

Amino Acid Sequence↗

PubMed2005

The Arabidopsis vitamin E pathway gene5-1 mutant reveals a critical role for phytol kinase in seed tocopherol biosynthesis.

We report the identification and characterization of a low tocopherol Arabidopsis thaliana mutant, vitamin E pathway gene5-1 (vte5-1), with seed tocopherol levels reduced to 20% of the wild type. Map-based identification of the responsible mutation identified a G-->A transition, resulting in the introduction of a stop codon in At5g04490, a previously unannotated gene, which we named VTE5. Complementation of the mutation with the wild-type transgene largely restored the wild-type tocopherol phenotype. A knockout mutation of the Synechocystis sp PCC 6803 VTE5 homolog slr1652 reduced Synechocystis tocopherol levels by 50% or more. Bioinformatic analysis of VTE5 and slr1652 indicated modest similarity to dolichol kinase. Analysis of extracts from Arabidopsis and Synechocystis mutants revealed increased accumulation of free phytol. Heterologous expression of these genes in Escherichia coli supplemented with free phytol and in vitro assays of recombinant protein produced phytylmonophosphate, suggesting that VTE5 and slr1652 encode phytol kinases. The phenotype of the vte5-1 mutant is consistent with the hypothesis that chlorophyll degradation-derived phytol serves as an important intermediate in seed tocopherol synthesis and forces reevaluation of the role of geranylgeranyl diphosphate reductase in tocopherol biosynthesis.

Amino Acid Sequence↗

PubMed2006

Rapid transcriptome changes induced by cytosolic Ca2+ transients reveal ABRE-related sequences as Ca2+-responsive cis elements in Arabidopsis.

The regulation of gene expression by cellular calcium is crucial for plant defense against biotic and abiotic stresses. However, the number of genes known to respond to specific transient calcium signals is limited, and as yet there is no definition of a calcium-responsive cis element in plants. Here, we generated specific cytosolic calcium transients in intact Arabidopsis thaliana seedlings and linked them to early transcriptome changes, followed by bioinformatic analysis of the responsive genes. A cytosolic calcium transient induced by calmodulin antagonists and blocked by lanthanides was characterized using aequorin-based luminometry and photon imaging. Analysis of transcriptome changes revealed 230 calcium-responsive genes, of which 162 were upregulated and 68 were downregulated. These include known early stress-responsive genes as well as genes of unknown function. Analysis of their upstream regions revealed, exclusively in the upregulated genes, a highly significant occurrence of a consensus sequence (P < 10(-13)) comprising two abscisic acid-specific cis elements: the abscisic acid-responsive element (ABRE; CACGTG[T/C/G]) and its coupling element ([C/A]ACGCG[T/C/G]) [corrected] Finally, we show that a tetramer of the ABRE cis element is sufficient to confer transcriptional activation in response to cytosolic Ca(2+) transients. Thus, at least for some specific Ca(2+) transients and motif combinations, ABREs function as Ca(2+)-responsive cis elements.

Arabidopsis↗

PubMed2006

Identification of important regions for ethylene binding and signaling in the transmembrane domain of the ETR1 ethylene receptor of Arabidopsis.

The ethylene binding domain (EBD) of the Arabidopsis thaliana ETR1 receptor is modeled as three membrane-spanning helices. We surveyed ethylene binding activity in different kingdoms and performed a bioinformatic analysis of the EBD. Ethylene binding is confined to land plants, Chara, and a group of cyanobacteria but is largely absent in other organisms, consistent with our finding that EBD-like sequences are overrepresented among plant and cyanobacterial species. We made amino acid substitutions in 37 partially or completely conserved residues of the EBD and assayed their effects on ethylene binding and signaling. Mutations primarily in residues in Helices I and II midregions eliminated ethylene binding and conferred constitutive signaling, consistent with the inverse-agonist model of ethylene receptor signaling and indicating that these residues define the ethylene binding pocket. The largest class of mutations, clustered near the cytoplasmic ends of Helices I and III, gave normal ethylene binding activity yet still conferred constitutive signaling. Therefore, these residues may play a role in turning off the signal transmitter domain of the receptor. By contrast, only two mutations were loss of function with respect to signaling. These findings yield insight into the structure and function of the EBD and suggest a conserved role of the EBD as a negative regulator of the signal transmitter domain.

Amino Acid Sequence↗

PubMed2004

Structure of Mesorhizobium loti arylamine N-acetyltransferase 1.

The arylamine N-acetyltransferase (NAT) enzymes have been found in a broad range of both eukaryotic and prokaryotic organisms. The NAT enzymes catalyse the transfer of an acetyl group from acetyl Co-enzyme A onto the terminal nitrogen of a range of arylamine, hydrazine and arylhydrazine compounds. Recently, several NAT structures have been reported from different prokaryotic sources including Salmonella typhimurium, Mycobacterium smegmatis and Pseudomonas aeruginosa. Bioinformatics analysis of the Mesorhizobium loti genome revealed two NAT paralogues, the first example of multiple NAT isoenzymes in a eubacterial organism. The M. loti NAT 1 enzyme was recombinantly expressed and purified for X-ray crystallographic studies. The purified enzyme was crystallized in 0.5 M Ca(OAc)2, 16% PEG 3350, 0.1 M Tris-HCl pH 8.5 using the sitting-drop vapour-diffusion method. A data set diffracting to 2.0 A was collected from a single crystal at 100 K. The crystal belongs to the orthorhombic spacegroup P2(1)2(1)2(1), with unit-cell parameters a = 53.2, b = 97.3, c = 114.3 A. The structure was refined to a final free-R factor of 24.8%. The structure reveals that despite low sequence homology, M. loti NAT1 shares the common fold as reported in previous NAT structures and exhibits the same catalytic triad of residues (Cys-His-Asp) in the active site.

Alphaproteobacteria↗

PubMed2026

Prenatal Alcohol Exposure Produces Selective Changes in Neuroimmune Gene Expression Across Brain Regions of Adult Mice.

BACKGROUND: An overwhelming body of evidence suggests neuroimmune dysfunction as a key underlying mechanism of fetal alcohol spectrum disorder (FASD)-associated adverse central nervous system (CNS) outcomes. While few studies have highlighted the lingering effects of prenatal alcohol exposure (PAE) on producing specific immune factors, others suggest a primed neuroimmune state in adulthood, in which a proinflammatory bias is unmasked following subsequent immune activation in later life. However, the PAE-induced neuroimmune landscape in adulthood remains poorly defined. We hypothesized that PAE induces long-term changes in gene expression linked to neuroimmune function that may be brain region-specific. METHODS: Using long-read next-generation RNA sequencing of brain tissues from a previously established model of a moderate PAE in mice, we compared across six regions: medial prefrontal cortex (mPFC), anterior cingulate cortex (ACC), hypothalamus, hippocampus, midbrain, and medulla. A comprehensive bioinformatics analysis investigated PAE-induced changes, dysregulated gene pathways, and transcriptional regulators with a focus on neuroimmune function. RESULTS: Our data identified at least 60 differentially expressed genes per brain region, many of which were associated with neuroimmune function. Upregulation of multiple pro-inflammatory factors and pathways was observed, suggesting ongoing baseline neuroimmune activation, potentially involving PXR, TNF, TLR4, the complement pathway, and various cytokine and chemokine signaling. A comparative analysis identified multiple upstream transcriptional regulators across multiple brain regions, including MECP2, TCF7L2, and IL-4. Importantly, this unbiased analysis revealed heterogeneity across brain regions in the activation of canonical immune pathways and highlighted previously unprecedented roles of pathways such as PXR, matrix metalloproteases, and cytokine signaling (e.g., IL-15, IL-27, IL-17) in PAE. CONCLUSIONS: PAE creates a unique inflammatory signature in the adult brain, even in the absence of secondary injury, with novel patterns of region-specific changes in genes implicated in glial-immune function. These data identify potential immune targets to elucidate the mechanisms underlying behavioral dysfunction and provide a framework for future therapeutic interventions.

Animals↗

PubMed2006

An integrative approach for the identification of quantitative trait loci.

The genetic dissection of complex traits is one of the most difficult and most important challenges facing science today. We discuss here an integrative approach to quantitative trait loci (QTL) mapping in mice. This approach makes use of the wealth of genetic tools available in mice, as well as the recent advances in genome sequence data already available for a number of inbred mouse strains. We have developed mapping strategies that allow a stepwise narrowing of a QTL mapping interval, prioritizing candidate genes for further analysis with the potential of identifying the most probable candidate gene for the given trait. This approach integrates traditional mapping tools, fine mapping tools, sequence-based analysis, bioinformatics and gene expression.

Animals↗

PubMed2006

Distinct comparative genomic hybridisation profiles in gastric mucosa-associated lymphoid tissue lymphomas with and without t(11;18)(q21;q21).

t(11;18)(q21;q21) occurs specifically in mucosa-associated lymphoid tissue (MALT) lymphoma and the translocation generates a functional API2-MALT1 fusion product that activates nuclear factor (NF)kappaB. t(11;18) positive lymphomas usually lack the chromosomal aberrations and microsatellite alterations frequently seen in the translocation-negative MALT lymphomas. To further understand their genetic differences, we investigated gastric MALT lymphomas with and without t(11;18) by comparative genomic hybridisation. In general, both chromosomal gains and losses were far more frequent in t(11;18)-negative (median = 3.4 imbalances) than t(11;18)-positive cases (median = 1.6 imbalances), with gains being more frequent than losses. Recurrent chromosomal gains involving whole or major parts of a chromosome were seen for chromosomes 3, 12, 18 and 22 (23%, 19%, 19% and 27% respectively). Discrete recurrent chromosomal gains were found at 9q34 (11/26 = 42%). Bioinformatic analysis of genes mapping to 9q34 revealed potential targets. Among them, TRAF2 and CARD9 are known interaction partners of BCL10, playing a role in NFkappaB activation. Interphase fluorescent in situ hybridisation confirmed genomic gain of the TRAF2, CARD9 and MALT1 loci in 5/6 and 2/2 cases showing chromosomal gains at 9q34 and 18q21 respectively. The results further highlight the genetic difference between MALT lymphomas with and without t(11;18). Moreover, our findings suggest that genomic gain of genes that modulate NFkappaB activation, such as MALT1, TRAF2 and CARD9, may play a role in the pathogenesis of the translocation-negative MALT lymphoma.

Adaptor Proteins, Signal Transducing↗

PubMed2006

Bacterial nucleoid dynamics: oxidative stress response in Staphylococcus aureus.

A single-molecule-imaging technique, atomic force microscopy (AFM) was applied to the analyses of the genome architecture of Staphylococcus aureus. The staphylococcal cells on a cover glass were subjected to a mild lysis procedure that had maintained the fundamental structural units in Escherichia coli. The nucleoids were found to consist of fibrous structures with diameters of 80 and 40 nm. This feature was shared with the E. coli nucleoid. However, whereas the E. coli nucleoid dynamically changed its structure to a highly compacted one towards the stationary phase, the S. aureus nucleoid never underwent such a tight compaction under a normal growth condition. Bioinformatic analysis suggested that this was attributable to the lack of IHF that regulate the expression of a nucleoid protein, Dps, required for nucleoid compaction in E. coli. On the other hand, under oxidative conditions, MrgA (a staphylococcal Dps homolog) was over-expressed and a drastic compaction of the nucleoid was detected. A knock-out mutant of the gene encoding the transcription factor (perR) constitutively expressed mrgA, and its nucleoid was compacted without the oxidative stresses. The regulatory mechanisms of Dps/MrgA expression and their biological significance were postulated in relation to the nucleoid compaction.

Bacterial Proteins↗

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↗