Locus control regions of mammalian β-globin gene clusters: combining phylogenetic analyses and experimental results to gain functional insights

Gene ◽  
1997 ◽  
Vol 205 (1-2) ◽  
pp. 73-94 ◽  
Author(s):  
Ross Hardison ◽  
Jerry L. Slightom ◽  
Deborah L. Gumucio ◽  
Morris Goodman ◽  
Nikola Stojanovic ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Globin Gene ◽  
Gene Clusters ◽  
Experimental Results ◽  
Locus Control Regions ◽  
Control Regions

Locus control regions

2003 ◽  
pp. 397-409
Author(s):  
Xiangdong Fang ◽  
Kenneth R. Peterson ◽  
Qiliang Li ◽  
George Stamatoyannopoulos
Keyword(s):  
Locus Control Regions ◽  
Control Regions

scholarly journals Expression of the chicken beta-globin gene cluster in mice: correct developmental expression and distributed control.

1995 ◽  
Vol 15 (1) ◽  
pp. 407-414 ◽  
Author(s):  
M M Mason ◽  
E Lee ◽  
H Westphal ◽  
M Reitman
Keyword(s):  
Developmental Stage ◽  
Globin Gene ◽  
Stage Iv ◽  
Gene Clusters ◽  
Developmental Expression ◽  
Single Element ◽  
Globin Genes ◽  
Beta Globin ◽  
Variable Expression ◽  
Hypersensitive Sites

To investigate the regulation of gene clusters, we introduced the entire chicken beta-globin cluster into mice. This 35-kb region includes the four globin genes (rho-beta H-beta A-epsilon), the four upstream hypersensitive sites, and the intergenic beta A/epsilon enhancer. The chicken globins are not arranged in order of developmental expression, which is unlike the case for the human beta-globin cluster, in which gene order plays a role in the regulation of globin expression. Mice carrying the chicken cluster expressed the transgenes with the same developmental patterns as seen in the chicken. Therefore, stage-specific erythroid transcriptional milieus existed before the divergence of birds and mammals and have been conserved since then. Mice bearing the complete cluster except for a deletion removing the beta A/epsilon enhancer displayed markedly reduced expression of the beta H, beta A, and epsilon genes with efficient (but variable) rho expression. Mice carrying the four genes and beta A/epsilon enhancer but without the upstream hypersensitive sites showed reduced expression of rho, beta H, and beta A, with variable expression of epsilon. We conclude that (i) all of the genes (except possibly rho) are under the control of both the upstream hypersensitive sites and the enhancer, (ii) the influence of the control elements can extend beyond the nearest active gene, (iii) a single element (the enhancer) can influence more than one gene in a single developmental stage, (iv) the enhancer can work bidirectionally, and (v) neither the upstream sites (as a group) nor the enhancer showed developmental stage specificity. Thus, the regulation of this cluster is achieved by interaction of two distinct control regions with each of the globin genes.

scholarly journals Pan-genome diversification and recombination in Cronobacter sakazakii, an opportunistic pathogen in neonates, and insights to its xerotolerant lifestyle

2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Isaiah Paolo A. Lee ◽  
Cheryl P. Andam
Keyword(s):  
Phylogenetic Analyses ◽  
Gene Clusters ◽  
Genomic Diversity ◽  
Ecological Niches ◽  
Cronobacter Sakazakii ◽  
Type Vi Secretion System ◽  
Accessory Gene ◽  
Pan Genome ◽  
Accessory Genes ◽  
Mannose Metabolism

Abstract Background Cronobacter sakazakii is an emerging opportunistic bacterial pathogen known to cause neonatal and pediatric infections, including meningitis, necrotizing enterocolitis, and bacteremia. Multiple disease outbreaks of C. sakazakii have been documented in the past few decades, yet little is known of its genomic diversity, adaptation, and evolution. Here, we analyzed the pan-genome characteristics and phylogenetic relationships of 237 genomes of C. sakazakii and 48 genomes of related Cronobacter species isolated from diverse sources. Results The C. sakazakii pan-genome contains 17,158 orthologous gene clusters, and approximately 19.5% of these constitute the core genome. Phylogenetic analyses reveal the presence of at least ten deep branching monophyletic lineages indicative of ancestral diversification. We detected enrichment of functions involved in proton transport and rotational mechanism in accessory genes exclusively found in human-derived strains. In environment-exclusive accessory genes, we detected enrichment for those involved in tryptophan biosynthesis and indole metabolism. However, we did not find significantly enriched gene functions for those genes exclusively found in food strains. The most frequently detected virulence genes are those that encode proteins associated with chemotaxis, enterobactin synthesis, ferrienterobactin transporter, type VI secretion system, galactose metabolism, and mannose metabolism. The genes fos which encodes resistance against fosfomycin, a broad-spectrum cell wall synthesis inhibitor, and mdf(A) which encodes a multidrug efflux transporter were found in nearly all genomes. We found that a total of 2991 genes in the pan-genome have had a history of recombination. Many of the most frequently recombined genes are associated with nutrient acquisition, metabolism and toxin production. Conclusions Overall, our results indicate that the presence of a large accessory gene pool, ability to switch between ecological niches, a diverse suite of antibiotic resistance, virulence and niche-specific genes, and frequent recombination partly explain the remarkable adaptability of C. sakazakii within and outside the human host. These findings provide critical insights that can help define the development of effective disease surveillance and control strategies for Cronobacter-related diseases.

scholarly journals Developmental switch in the relative expression of the alpha 1- and alpha 2-globin genes in humans and in transgenic mice

Blood ◽  
1992 ◽  
Vol 79 (9) ◽  
pp. 2471-2474 ◽  
Author(s):  
M Albitar ◽  
FE Cash ◽  
C Peschle ◽  
SA Liebhaber
Keyword(s):  
Transgenic Mice ◽  
Globin Gene ◽  
Gene Activation ◽  
Experimental System ◽  
Gene Clusters ◽  
Globin Genes ◽  
Beta Globin ◽  
Relative Expression ◽  
Structural Identity ◽  
Alpha Globin

Abstract Human alpha-globin is encoded by two adjacent genes, alpha 2 and alpha 1. Despite their remarkable level of structural identity, the more 5′ (alpha 2) gene is the major alpha-globin locus in the normal adult, expressed at 2.6-fold higher levels than the adjacent and more 3′ (alpha 1) globin gene. In light of the well-characterized pattern of gene activation in the human alpha- and beta-globin gene clusters during development, we considered the possibility that the relative expression of these two alpha-globin loci might be developmentally controlled. Analysis of human embryonic and early fetal erythroid RNA samples confirmed this possibility; levels of mRNA encoded by the two alpha-globin loci are equal in the embryo and subsequently shift to dominant expression of the alpha 2-globin locus at week 8 in utero. In transgenic mice carrying the entire human alpha-globin cluster (except for the theta gene) we show the same shift from equal expression of the alpha 1- and alpha 2-globin loci at the embryonic stage to predominance of the alpha 2-globin locus in the adult. These data demonstrate a switch in the expression of the two adjacent alpha-globin genes during the embryonic-to-fetal switch in erythroid development and provide an experimental system for its further characterization.

scholarly journals Expanding magnetic organelle biogenesis in the domain Bacteria

Microbiome ◽  
2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Wei Lin ◽  
Wensi Zhang ◽  
Greig A. Paterson ◽  
Qiyun Zhu ◽  
Xiang Zhao ◽  
...  
Keyword(s):  
Phylogenetic Analyses ◽  
Biological Significance ◽  
Gene Clusters ◽  
Magnetic Sensors ◽  
Evolutionary Origin ◽  
Phylogenomic Analysis ◽  
Organelle Biogenesis ◽  
Taxonomic Distribution ◽  
Origin And Evolution ◽  
Bacterial Phyla

Abstract Background The discovery of membrane-enclosed, metabolically functional organelles in Bacteria has transformed our understanding of the subcellular complexity of prokaryotic cells. Biomineralization of magnetic nanoparticles within magnetosomes by magnetotactic bacteria (MTB) is a fascinating example of prokaryotic organelles. Magnetosomes, as nano-sized magnetic sensors in MTB, facilitate cell navigation along the local geomagnetic field, a behaviour referred to as magnetotaxis or microbial magnetoreception. Recent discovery of novel MTB outside the traditionally recognized taxonomic lineages suggests that MTB diversity across the domain Bacteria are considerably underestimated, which limits understanding of the taxonomic distribution and evolutionary origin of magnetosome organelle biogenesis. Results Here, we perform the most comprehensive metagenomic analysis available of MTB communities and reconstruct metagenome-assembled MTB genomes from diverse ecosystems. Discovery of MTB in acidic peatland soils suggests widespread MTB occurrence in waterlogged soils in addition to subaqueous sediments and water bodies. A total of 168 MTB draft genomes have been reconstructed, which represent nearly a 3-fold increase over the number currently available and more than double the known MTB species at the genome level. Phylogenomic analysis reveals that these genomes belong to 13 Bacterial phyla, six of which were previously not known to include MTB. These findings indicate a much wider taxonomic distribution of magnetosome organelle biogenesis across the domain Bacteria than previously thought. Comparative genome analysis reveals a vast diversity of magnetosome gene clusters involved in magnetosomal biogenesis in terms of gene content and synteny residing in distinct taxonomic lineages. Phylogenetic analyses of core magnetosome proteins in this largest available and taxonomically diverse dataset support an unexpectedly early evolutionary origin of magnetosome biomineralization, likely ancestral to the origin of the domain Bacteria. Conclusions These findings expand the taxonomic and phylogenetic diversity of MTB across the domain Bacteria and shed new light on the origin and evolution of microbial magnetoreception. Potential biogenesis of the magnetosome organelle in the close descendants of the last bacterial common ancestor has important implications for our understanding of the evolutionary history of bacterial cellular complexity and emphasizes the biological significance of the magnetosome organelle.

scholarly journals DNA polymorphism and molecular pathology of the human globin gene clusters

1985 ◽  
Vol 70 (1) ◽  
pp. 95-99 ◽  
Author(s):  
Stylianos E. Antonarakis ◽  
Haig H. Kazazian ◽  
Stuart H. Orkin
Keyword(s):  
Molecular Pathology ◽  
Dna Polymorphism ◽  
Globin Gene ◽  
Gene Clusters

Genetic recombination as a major cause of mutagenesis in the human globin gene clusters

2009 ◽  
Vol 42 (18) ◽  
pp. 1839-1850 ◽  
Author(s):  
Joseph Borg ◽  
Marianthi Georgitsi ◽  
Vassiliki Aleporou-Marinou ◽  
Panagoula Kollia ◽  
George P. Patrinos
Keyword(s):  
Genetic Recombination ◽  
Globin Gene ◽  
Gene Clusters

scholarly journals Characterization of the Nodularin Synthetase Gene Cluster and Proposed Theory of the Evolution of Cyanobacterial Hepatotoxins

2004 ◽  
Vol 70 (11) ◽  
pp. 6353-6362 ◽  
Author(s):  
Michelle C. Moffitt ◽  
Brett A. Neilan
Keyword(s):  
Gene Cluster ◽  
Rational Design ◽  
Polyketide Synthase ◽  
Alternative Hypothesis ◽  
Phylogenetic Analyses ◽  
Cyanobacterial Bloom ◽  
Gene Clusters ◽  
Biosynthetic Gene Cluster ◽  
Biosynthetic Gene ◽  
Microcystin Synthetase

ABSTRACT Nodularia spumigena is a bloom-forming cyanobacterium which produces the hepatotoxin nodularin. The complete gene cluster encoding the enzymatic machinery required for the biosynthesis of nodularin in N. spumigena strain NSOR10 was sequenced and characterized. The 48-kb gene cluster consists of nine open reading frames (ORFs), ndaA to ndaI, which are transcribed from a bidirectional regulatory promoter region and encode nonribosomal peptide synthetase modules, polyketide synthase modules, and tailoring enzymes. The ORFs flanking the nda gene cluster in the genome of N. spumigena strain NSOR10 were identified, and one of them was found to encode a protein with homology to previously characterized transposases. Putative transposases are also associated with the structurally related microcystin synthetase (mcy) gene clusters derived from three cyanobacterial strains, indicating a possible mechanism for the distribution of these biosynthetic gene clusters between various cyanobacterial genera. We propose an alternative hypothesis for hepatotoxin evolution in cyanobacteria based on the results of comparative and phylogenetic analyses of the nda and mcy gene clusters. These analyses suggested that nodularin synthetase evolved from a microcystin synthetase progenitor. The identification of the nodularin biosynthetic gene cluster and evolution of hepatotoxicity in cyanobacteria reported in this study may be valuable for future studies on toxic cyanobacterial bloom formation. In addition, an appreciation of the natural evolution of nonribosomal biosynthetic pathways will be vital for future combinatorial engineering and rational design of novel metabolites and pharmaceuticals.

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