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PubMed1995

Complete sequence of a sea lamprey (Petromyzon marinus) mitochondrial genome: early establishment of the vertebrate genome organization.

The complete nucleotide sequence of a sea lamprey (Petromyzon marinus) mitochondrial genome has been determined. The lamprey genome is 16,201 bp in length and contains genes for 13 proteins, two rRNAs, 22 tRNAs and two major noncoding regions. The order and transcriptional polarities of protein-coding genes are basically identical to those of other chordate mtDNAs, demonstrating that the common mitochondrial gene organization of vertebrates was established at an early stage of vertebrate evolution. The two major noncoding regions are separated by two tRNA genes. The first region probably functions as the control region because it contains distinctive conserved sequence blocks (CSB-II and III) common to other vertebrate control regions. The central conserved domain observed in other vertebrate control regions is not found in the lamprey, suggesting that it is a recently evolved functional domain in vertebrates. Noncoding segments are not found in the expected position of the origin of replication for the second strand, suggesting either that one of the tRNA genes has a dual function or that the second noncoding region may function as the second-strand origin. The base composition at the wobble positions of fourfold degenerate codon families is highly biased toward thymine (32.7%). Values of GC- and AT-skew are typical of vertebrate mitochondrial genomes.

Amino Acid Sequence↗
PubMed1996

Clonal evolution in B-lineage acute lymphoblastic leukemia by contemporaneous VH-VH gene replacements and VH-DJH gene rearrangements.

B-cell acute lymphoblastic leukemia (B-ALL), more frequently than any other B-lineage neoplasm, exhibits oligoclonal Ig heavy chain (IgH) gene rearrangement in 15% to 43% of all cases studied. To study the molecular processes that promote multiple IgH rearrangements, a comprehensive sequence analysis of a B-ALL case was performed in which seven clonal IgH gene rearrangements were identified. The genetic profiles suggested that a single leukemic progenitor clone evolved into several subclones through dual processes of variable (VH) to preexisting diversity-joining (DJH) gene segment rearrangement and VH to VH gene replacement. Predominant IgH-V usage and the uniquely rearranged clonotype-specific VHDJH region gene sequences were identified using a novel DNA-based gene amplification strategy. Polymerase chain reaction (PCR) was directed by an IgH-J generic primer and a complement of family-specific IgH-V primers that defined the major B-cell IgH-V gene usage. Clonality of rearranged VHDJH bands was substantiated by high resolution denaturant gel electrophoretic analysis. Sequence patterns of the amplified VHDJH fragments segregated into two groups defined by common DJH sequences. Partial N region homology at the VHD junction as well as shared DJH sequences firmly established VH to VHDJH gene replacement as a mechanism generating clonal evolution in one group. In the second subset, oligoclonality was propagated by independent VH gene rearrangements to a common DJH precursor. The contributions of all clonal Ig-VHDJH repertoires for each group was approximately 50% and reflected a symmetric distribution of leukemic subclones generated by either process. Thus, oligoclonal rearrangements evolved by two independent, yet seemingly contemporaneous molecular genetic mechanisms. All seven clones displayed nonfunctional Ig-VHDJH recombinations. These observations may have relevance to the recombinatorial opportunities available during normal B-cell maturation.

Base Sequence↗
PubMed1996

Evidence of reciprocity of bcl-2 and p53 expression in human colorectal adenomas and carcinomas.

Evidence of accumulating for the failure of apoptosis as an important factor in the evolution of colorectal cancer and its poor response to adjuvant therapy. The proto-oncogene bcl-2 suppresses apoptosis. Its expression could provide an important survival advantage permitting the development of colorectal cancer. The expression of bcl-2 and p53 was determined by immunohistochemistry in 47 samples of histologically normal colonic mucosa, 19 adenomas and 53 adenocarcinomas. Expression of bcl-2 in colonic crypts > 5 cm from the tumours was confined to crypt bases but was more extensive and intense in normal crypts < 5 mm from cancers. A higher proportion of adenomas (63.2%) than carcinomas (36.5%) expressed bcl-2 (P < 0.05). A lower proportion of adenomas (31.6%) than carcinomas (62.3%) expressed p53 (P < 0.02). A total of 26.3% of adenomas and 22% of carcinomas expressed both bcl-2 and p53. To determine whether these samples contained cells which expressed both proteins, a dual staining technique for bcl-2 and p53 was used. Only 1/19 adenomas and 2/53 carcinomas contained cells immunopositive for both bcl-2 and p53. Moreover there was evidence of reciprocity of expression of bcl-2 and p53 in these three double staining neoplasms. We suggest that bcl-2 provides a survival advantage in the proliferative compartment of normal crypts and colorectal neoplasms. However, its expression is lost during the evolution from adenoma to carcinoma, whereas p53 expression is increased, an event generally coincident with the expression of stabilised p53, which we presume to represent the mutant form.

Adenocarcinoma↗
PubMed2004

The complete nucleotide sequence of the resistance plasmid R478: defining the backbone components of incompatibility group H conjugative plasmids through comparative genomics.

Horizontal transfer of resistance determinants amongst bacteria can be achieved by conjugative plasmid DNA elements. We have determined the complete 274,762 bp sequence of the incompatibility group H (IncH) plasmid R478, originally isolated from the Gram negative opportunistic pathogen Serratia marcescens. This self-transferable extrachromosomal genetic element contains 295 predicted genes, of which 144 are highly similar to coding sequences of IncH plasmids R27 and pHCM1. The regions of similarity among these three IncH plasmids principally encode core plasmid determinants (i.e., replication, partitioning and stability, and conjugative transfer) and we conducted a comparative analysis to define the minimal IncHI plasmid backbone determinants. No resistance determinants are included in the backbone and most of the sequences unique to R478 were contained in a large contiguous region between the two transfer regions. These findings indicate that plasmid evolution occurs through gene acquisition/loss predominantly in regions outside of the core determinants. Furthermore, a modular evolution for R478 was signified by the presence of gene neighbors or operons that were highly related to sequences from a wide range of chromosomal, transposon, and plasmid elements. The conjugative transfer regions are most similar to sequences encoded on SXT, Rts1, pCAR1, R391, and pRS241d. The dual partitioning modules encoded on R478 resemble numerous sequences; including pMT1, pCTX-M3, pCP301, P1, P7, and pB171. R478 also codes for resistance to tetracycline (Tn10), chloramphenicol (cat), kanamycin (aphA), mercury (similar to Tn21), silver (similar to pMG101), copper (similar to pRJ1004), arsenic (similar to pYV), and tellurite (two separate regions similar to IncHI2 ter determinants and IncP kla determinants). Other R478-encoded sequences are related to Tn7, IS26, tus, mucAB, and hok, where the latter is surrounded by insLKJ, and could potentially be involved in post-segregation killing. The similarity to a diverse set of bacterial sequences highlights the ability of horizontally transferable DNA elements to acquire and disseminate genetic traits through the bacterial gene pool.

Base Sequence↗
PubMed2003

Photocatalytic degradation of E. coliform in water.

This study aims to further investigate the total mineralization of the bacteria to the extent of death and cell-mass inactivation using a TiO2-Fe2O3 membrane photocatalytic oxidation reactor. Experimental results clearly indicated that dissolved oxygen (DO), hydraulic retention time (HRT) and concentration of the model bacteria (Escherichia coliform) affected the removal efficiency. It was found that the ultimate removal efficiency was 99% at DO level of 21.34 mg/l, HRT at 60s and high concentration of E. coli at 10(9)CFU/ml. The morphologic studies also showed that E. coliform could be further mineralized into CO2 and H2O. Dissolved organic carbon, pH and gas chromatograph analysis had justified most importantly the evolution of CO2. Experimental results revealed that the photomineralization rate of E. coliform followed pseudo-first-order kinetics by the role of DO. The derived empirical models were found consistent with the proposed reaction pathways of a combined UV breakdown on mass cell and a dual-site Langmuir-Hinshelwood mechanism where the rate-controlling step is the surface interaction between the adsorbed cleavage bacterial cells and hydroxyl radicals.

Adsorption↗
PubMed2001

From xeroderma pigmentosum to the biological clock contributions of Dirk Bootsma to human genetics.

This paper commemorates the multiple contributions of Dirk Bootsma to human genetics. During a scientific 'Bootsma' cruise on his sailing-boat 'de Losbol', we visit a variety of scenery locations along the lakes and canals in Friesland, passing the highlights of Dirk Bootsma's scientific oeuvre. Departing from 'de Fluessen', his homeport, with his PhD work on the effect of X-rays and UV on cell cycle progression, we head for the pioneering endeavours of his team on mapping genes on human chromosomes by cell hybridization. Next we explore the use of cell hybrids by the Bootsma team culminating in the molecular cloning of one of the first chromosomal breakpoints involved in oncogenesis: the bcr-abl fusion gene responsible for chronic myelocytic leukemia. This seminal achievement enabled later development of new methods for early detection and very promising therapeutic intervention. A series of highlights at the horizon constitute the contributions of his team to the field of DNA repair, beginning with the discovery of genetic heterogeneity in the repair syndrome xeroderma pigmentosum (XP) followed later by the cloning of a large number of human repair genes. This led to the discovery that DNA repair is strongly conserved in evolution rendering knowledge from yeast relevant for mammals and vice versa. In addition, it resolved the molecular basis of several repair syndromes and permitted functional analysis of the encoded proteins. Another milestone is the discovery of the surprising connection between DNA repair and transcription initiation via the dual functional TFIIH complex in collaboration with Jean-Marc Egly et al. in Strasbourg. This provided an explanation for many puzzling clinical features and triggered a novel concept in human genetics: the existence of repair/transcription syndromes. The generation of many mouse mutants carrying defects in repair pathways yielded valuable models for assessing the clinical relevance of DNA repair including carcinogenesis and the identification of a link between DNA damage and premature aging. His team also opened a fascinating area of cell biology with the analysis of repair and transcription in living cells. A final surprising evolutionary twist was the discovery that photolyases designed for the light-dependent repair of UV-induced DNA lesions appeared to be adopted for driving the mammalian biological clock. The latter indicates that it is time to return to 'de Fluessen', where we will consider briefly the merits of Dirk Bootsma for Dutch science in general.

Amino Acid Sequence↗
PubMed1999

Influence of methodology on the presence and extent of mismatching between 99mTc-MIBI and 123I-BMIPP in myocardial viability studies.

UNLABELLED: Discordant uptake (mismatching) of 123I-labeled beta-methyl-piodophenyl-pentadecanoic acid (BMIPP) less than 99mTc-labeled methoxyisobutyl isonitrile (MIBI) is a good predictor of myocardial viability. However, methodological factors can influence assessment of the presence of mismatching because of differences in background activity between the tracers. In this study, we investigated the influence of methodological parameters on the mismatching between BMIPP and MIBI in patients with chronic ischemic heart disease. METHODS: Polar maps were created to quantify the extent of mismatched tissue measured in 10 patients with myocardial infarction according to three methods for data processing: no correction, subtraction of background activity measured in the left ventricle cavity and dual-window scatter correction. Mismatching was expressed as a percentage of the surface of the left ventricle globally as well as for each arterial territory using a BMIPP uptake of at least 10% less than MIBI as the threshold. The results of dobutamine stress echocardiography and the evolution of the regional contractility at 6-mo follow-up were used as references. RESULTS: Mean background activity in the ventricle cavity was 9.3% of the maximum activity for MIBI and 21.4% for BMIPP before, and 2.8% and 8.3% after scatter correction. Fourteen arterial vascular territories demonstrated baseline wall-motion abnormalities; 9 territories showed contractile reserve with dobutamine stress echocardiography. Significant mismatching was found in 5 of 14 regions without correction, 9 of 14 after scatter correction and 13 of 14 after background subtraction. Compared with the evolution of resting regional contractility at follow-up, optimal results were found when using the scatter-corrected data. Without correction, mismatching between BMIPP and MIBI was partially disguised because of the higher noise level in the iodine images. On the contrary, subtraction of background measured by means of a single region of interest overestimated the magnitude of mismatching due to the heterogeneous background distribution in the ventricular cavity. CONCLUSION: In quantifying the presence and extent of mismatching between MIBI and BMIPP in chronic ischemic heart disease, significant differences in the detection of viability are noted according to the acquisition and processing methods used. Scatter correction of the acquisition data is the most accurate and reliable method for identifying viable myocardium.

Fatty Acids↗
PubMed1994

[Technical problems posed by automatic treatment of arrhythmia by an implanted pacemaker].

The automatic treatment of arrhythmias by cardiac pacemakers requires a phase of recognition of the arrhythmia followed by its treatment. Different factors limit the analysis and recognition ranging from the quality of detection of spontaneous events to the recognition of the arrhythmias. Bipolar dual chamber pacing is essential: it allows minimisation of the detection of interference or cross talk between the atrial and ventricular chambers and better discrimination of episodes of rapid rhythm. The treatment algorithms are multiple, difficult to investigate in the laboratory, and their efficacy varies with the evolution of the pathology or with medical treatment. There is not a single response but a programme where the antitachycardia modes of pacing succeed one another until the reduction of the arrhythmia. This instability of treatment implies a capacity of memorization with a double objective: to authorize a posteriori diagnosis of the treated pathology and to analyse the evolution of the antitachycardia response. These diagnostic functions are also dependent on the quality of detection and pacing. The automaticity of the treatment, when essential, can only be envisaged in patients available for strict and regular clinical follow-up.

Arrhythmias, Cardiac↗
PubMed2006

Evidence for an early gene duplication event in the evolution of the mitochondrial transcription factor B family and maintenance of rRNA methyltransferase activity in human mtTFB1 and mtTFB2.

Most metazoans have two nuclear genes encoding orthologues of the well-characterized Saccharomyces cerevisiae mitochondrial transcription factor B (sc-mtTFB). This class of transcription factors is homologous to the bacterial KsgA family of rRNA methyltransferases, which in Escherichia coli dimethylates adjacent adenine residues in a stem-loop of the 16S rRNA. This posttranscriptional modification is conserved in most metazoan cytoplasmic and mitochondrial rRNAs. Homo sapiens mitochondrial transcription factor B1 (h-mtTFB1) possesses this enzymatic activity, implicating it as a dual-function protein involved in mitochondrial transcription and translation. Here we demonstrate that h-mtTFB2 also has rRNA methyltransferase activity but is a less efficient enzyme than h-mtTFB1. In contrast, sc-mtTFB has no detectable rRNA methyltransferase activity, correlating with the lack of the corresponding modification in the mitochondrial rRNA of budding yeast. Based on these results, and reports that Drosophila melanogaster mtTFB1 and mtTFB2 do not have completely overlapping functions, we propose a model for human mtDNA regulation that takes into account h-mtTFB1 and h-mtTFB2 likely having partially redundant transcription factor and rRNA methyltransferase functions. Finally, phylogenetic analyses of this family of proteins strongly suggest that the presence of two mtTFB homologues in metazoans is the result of a gene duplication event that occurred early in eukaryotic evolution prior to the divergence of fungi and metazoans. This model suggests that, after the gene duplication event, differential selective pressures on the rRNA methyltransferase and transcription factor activities of mtTFB genes occurred, with extreme cases culminating in the loss of one of the paralogous genes in certain species.

Animals↗
PubMed2005

The dual origin hypothesis: an evolutionary brain-behavior framework for analyzing psychiatric disorders.

According to the dual origin hypothesis, the cerebral cortex of higher mammals evolved from two primordial brain structures, the amygdala and hippocampal formation. This developmental process defines the orderly principles of cortical connectivity and gives rise to functionally distinct ventral and dorsal systems within the cerebrum. This paper reviews the basic features of the dual origin theory. This model is then applied to understanding symptom production in a number of psychiatric illnesses, with particular reference to recent structural and functional imaging studies. In this paper I propose that psychiatric symptoms can be conceptualized as arising from abnormal processing within dorsal (time-space-motility) or ventral (meaning-motivation) systems, or from a disturbance in the functional interaction/balance between them. Within this framework, one can identify symptom-specific correlations that cross-traditional diagnostic boundaries, as well as potential mechanisms that may explain biologically valid diagnostic entities. Integrating evolutionary, connectional and functional bases across multiple species, the dual origin hypothesis offers a powerful neural systems model to help organize our understanding of psychiatric illness, therein suggesting novel approaches to diagnosis, prevention and treatment.

Animals↗
PubMed1995

Chemical studies on the possible existence of life on Mars.

Although there is no direct evidence yet for the existence of life on Mars, it is reasonable to conclude that the emergence of life on Earth, which appears to have been controlled by universal laws of physics and chemistry, may have been repeated elsewhere in the universe. The dual approach of synthesis and analysis in our experimental studies has provided ample evidence in support of this hypothesis.

Aluminum Silicates↗
PubMed2005

Ultrafast intermolecular hydrogen bond dynamics in the excited state of fluorenone.

Steady-state fluorescence and time-resolved absorption measurements in pico- and femtosecond time domain have been used to investigate the dynamics of hydrogen bond in the excited singlet (S(1)) state of fluorenone in alcoholic solvents. A comparison of the features of the steady-state fluorescence spectra of fluorenone in various kinds of media demonstrates that two spectroscopically distinct forms of fluorenone in the S(1) state, namely the non-hydrogen-bonded (or free) molecule as well as the hydrogen-bonded complex, are responsible for the dual-fluorescence behavior of fluorenone in solutions of normal alcoholic solvents at room temperature (298 K). However, in 2,2,2-trifluoroethanol (TFE), a strong hydrogen bond donating solvent, emission from only the hydrogen-bonded complex is observed. Significant differences have also been observed in the temporal evolution of the absorption spectroscopic properties of the S(1) state of fluorenone in protic and aprotic solvents following photoexcitation using 400 nm laser pulses. An ultrafast component representing the solvent-induced vibrational energy relaxation (VER) process has been associated with the dynamics of the S(1) state of fluorenone in all kinds of solvents. However, in protic solvents, in addition to the VER process, further evolution of the spectroscopic and dynamical properties of the S(1) state have been observed because of repositioning of the hydrogen bonds around the carbonyl group. In normal alcohols, two different kinds of hydrogen-bonded complex of the fluorenone-alcohol system with different orientations of the hydrogen bond with respect to the carbonyl group and the molecular plane of fluorenone have been predicted. On the other hand, in TFE, formation of only one kind of hydrogen-bonded complex has been observed. These observations have been supported by theoretical calculations of the geometries of the hydrogen-bonded complexes in the ground and the excited states of fluorenone. Linear correlation between the lifetimes of the equilibration process occurring because of repositioning of the hydrogen bonds and Debye or longitudinal relaxation times of the normal alcoholic solvents establish the fact that, in weakly hydrogen bond donating solvents, the hydrogen bond dynamics can be described as merely a solvation process. Whereas, in TFE, hydrogen bond dynamics is better described by a process of conversion between two distinct excited states, namely, the non-hydrogen-bonded form and the hydrogen-bonded complex.

Journal Article↗
PubMed2000

Thymic neuroendocrine self-antigens. Role in T-cell development and central T-cell self-tolerance.

The repertoire of thymic neuroendocrine precursors plays a dual role in T-cell differentiation as the source of either cryptocrine accessory signals in T-cell development or neuroendocrine self-antigens presented by the thymic major histocompatibility complex (MHC) machinery. Thymic neuroendocrine self-antigens usually correspond to peptide sequences highly conserved during the evolution of one family. The thymic presentation of some neuroendocrine self-antigens is not restricted by MHC alleles. Oxytocin (OT) is the dominant peptide of the neurohypophysial family. It is expressed by thymic epithelial and nurse cells (TEC/TNCs) of different species. Ontogenetic studies have shown that the thymic expression of the OT gene precedes the hypothalamic one. Both OT and VP stimulate the phosphorylation of p125FAK and other focal adhesion-related proteins in murine immature T cells. These early cell activation events could play a role in the promotion of close interactions between thymic stromal cells and developing T cells. It is established that such interactions are fundamental for the progression of thymic T-cell differentiation. Insulin-like growth factor 2 (IGF-2) is the dominant thymic polypeptide of the insulin family. Using fetal thymic organ cultures (FTOCs), the inhibition of thymic IGF-2-mediated signaling was shown to block the early stages of T-cell differentiation. The treatment of FTOCs with an mAb anti-(pro)insulin had no effect on T-cell development. In an animal model of autoimmune type 1 diabetes (BB rat), thymic levels of (pro)insulin and IGF-1 mRNAs were normal both in diabetes-resistant and diabetes-prone BB rats. IGF-2 transcripts were clearly identified in all thymuses from diabetes-resistant adult (5-week) and young (2- and 5-days) BB rats. In marked contrast, the IGF-2 transcripts were absent and the IGF-2 protein was almost undetectable in +/- 80% of the thymuses from diabetes-prone adult and young BB rats. These data show that a defect of the thymic IGF-2-mediated tolerogenic function might play an important role in the pathophysiology of autoimmune Type 1 diabetes.

Adult↗
PubMed1998

Wnt signaling stabilizes the dual-function protein beta-catenin in diverse cell types.

The Wnt proteins constitute a large family of secreted signaling factors that performed a wide variety of inductive and regulatory functions in embryonic and postnatal development. In mammals, these include crucial roles in morphogenesis of the central nervous system, kidneys, limbs, and mammary glands. In recent years, much progress has been made in identifying components of the intracellular Wnt-1 signal transduction pathway through studies in Drosophila, C. elegans, Xenopus, and mammalian systems. Several features of this pathway are remarkably well conserved in evolution. A key component of the Wnt pathway is the cytoplasmic protein beta-catenin, whose stability is increased as a result of Wnt signaling. Although morphological effects of Wnt-1 in cell culture are seen in only a limited number of cell lines, we show here that responsiveness to Wnt-1 at the biochemical level is a common property of both epithelial and mesenchymal cells. The increased abundance of beta-catenin may have at least two functional consequences, depending on the subcellular localization of the protein. In some cell lines that respond to Wnt-1, there is a significant increase in the beta-catenin fraction associated with the plasma membrane, where the protein acts as a component of cell-cell adhesive junctions. In other cell types, the major effect of Wnt signaling is an increase in the cytosolic pool of beta-catenin. Increased abundance of this pool has recently been correlated with entry of beta-catenin into the nucleus, where the protein forms complexes with Tcf transcription factors and is thought to modulate the expression of specific genes. The dual consequences of Wnt signaling on cell adhesion and/or gene expression provide at least two potential mechanisms by which this key pathway can function in the regulation of morphogenesis.

Animals↗
PubMed2006

Structure of the mouse peptide N-glycanase-HR23 complex suggests co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.

Peptide N-glycanase removes N-linked oligosaccharides from misfolded glycoproteins as part of the endoplasmic reticulum-associated degradation pathway. This process involves the formation of a tight complex of peptide N-glycanase with Rad23 in yeast and the orthologous HR23 proteins in mammals. In addition to its function in endoplasmic reticulum-associated degradation, HR23 is also involved in DNA repair, where it plays an important role in damage recognition in complex with the xeroderma pigmentosum group C protein. To characterize the dual role of HR23, we have determined the high resolution crystal structure of the mouse peptide N-glycanase catalytic core in complex with the xeroderma pigmentosum group C binding domain from HR23B. Peptide N-glycanase features a large cleft between its catalytic cysteine protease core and zinc binding domain. Opposite the zinc binding domain is the HR23B-interacting region, and surprisingly, the complex interface is fundamentally different from the orthologous yeast peptide N-glycanase-Rad23 complex. Different regions on both proteins are involved in complex formation, revealing an amazing degree of divergence in the interaction between two highly homologous proteins. Furthermore, the mouse peptide N-glycanase-HR23B complex mimics the interaction between xeroderma pigmentosum group C and HR23B, thereby providing a first structural model of how the two proteins interact within the nucleotide excision repair cascade in higher eukaryotes. The different interaction interfaces of the xeroderma pigmentosum group C binding domains in yeast and mammals suggest a co-evolution of the endoplasmic reticulum-associated degradation and DNA repair pathways.

Amino Acid Sequence↗
PubMed2003

Gene duplication and other evolutionary strategies: from the RNA world to the future.

Beginning with a hypothetical RNA world, it is apparent that many evolutionary transitions led to the complexity of extant species. The duplication of genetic material is rooted in the RNA world. One of two major routes of gene amplification, retroposition, originated from mechanisms that facilitated the transition to DNA as hereditary material. Even in modern genomes the process of retroposition leads to genetic novelties including the duplication of protein and RNA coding genes, as well as regulatory elements and their juxtapositon. We examine whether and to what extent known evolutionary principles can be applied to an RNA-based world. We conclude that the major basic Neo-Darwinian principles that include amplification, variation and selection already governed evolution in the RNA and RNP worlds. In this hypothetical RNA world there were few restrictions on the exchange of genetic material and principles that acted as borders at later stages, such as Weismann's Barrier, the Central Dogma of Molecular Biology, or the Darwinian Threshold were absent or rudimentary. RNA was more than a gene: it had a dual role harboring, genotypic and phenotypic capabilities, often in the same molecule. Nuons, any discrete nucleic acid sequences, were selected on an individual basis as well as in groups. The performance and success of an individual nuon was markedly dependent on the type of other nuons in a given cell. In the RNA world the transition may already have begun towards the linkage of nuons to yield a composite linear RNA genome, an arrangement necessitating the origin of RNA processing. A concatenated genome may have curbed unlimited exchange of genetic material; concomitantly, selfish nuons were more difficult to purge. A linked genome may also have constituted the beginning of the phenotype/genotype separation. This division of tasks was expanded when templated protein biosynthesis led to the RNP world, and more so when DNA took over as genetic material. The aforementioned barriers and thresholds increased and the significance and extent of horizontal gene transfer fluctuated over major evolutionary transitions. At the dawn of the most recent transformation, a fast evolutionary transition that we will be witnessing in our life times, a form of Lamarckism is raising its head.

Animals↗
PubMed2006

Evolution of a basic helix-loop-helix protein from a transcriptional repressor to a plastid-resident regulatory factor: involvement in hypersensitive cell death in tobacco plants.

The tobacco gene NtWIN4 (Nicotiana tabacum wound-induced clone 4) is transiently up-regulated in response not only to wounding but also to pathogen attack. NtWIN4 encodes a putative basic helix-loop-helix protein with an apparent molecular mass of 28 kDa that exhibited clear nuclear transcription repression activity in Dual-Luciferase assays. However, immunoblotting indicated the existence of a 17-kDa form of NtWIN4 localized exclusively in tobacco leaf chloroplasts. Subsequent peptide dissection analyses with green fluorescent protein fusions revealed that a polypeptide of 81 amino acids starting at position 13 from the N terminus is maximally necessary for this localization. Further fine dissection analysis strongly suggested that the protein actually begins at the second Met located at position 27, yielding a signal peptide of 67 amino acids. However, the last C-terminal 15 amino acids overlap with the conserved basic region critical for DNA binding, so NtWIN4 presumably does not function as a transcription factor in planta. Transgenic tobacco plants constitutively overexpressing NtWIN4 demonstrated mortality with abnormal features, including albinism, and transient expression upon agroinfiltration resulted in distinct necrosis with a sharp decrease in chlorophyll content, consistent with the phenomenon known as chlorosis. Transgenic RNA interference tobacco plants exhibited reduced hypersensitive cell death, showing delayed tissue necrosis upon pathogen infection. These results suggest that NtWIN4 arose by divergence, becoming a chloroplast-resident factor from a nuclear transcriptional repressor by obtaining a transit peptide sequence, and that, upon translocation, it interacts with chloroplast components to induce hypersensitive cell death through chloroplast disruption, thereby contributing to plant stress responses.

Amino Acid Sequence↗
PubMed2001

Detection of single- and double-strand DNA breaks after traumatic brain injury in rats: comparison of in situ labeling techniques using DNA polymerase I, the Klenow fragment of DNA polymerase I, and terminal deoxynucleotidyl transferase.

DNA damage is a common sequela of traumatic brain injury (TBI). Available techniques for the in situ identification of DNA damage include DNA polymerase I-mediated biotin-dATP nick-translation (PANT), the Klenow fragment of DNA polymerase I-mediated biotin-dATP nick-end labeling (Klenow), and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL). While TUNEL has been widely utilized to detect primarily double-strand DNA breaks, the use of PANT to detect primarily single-strand DNA breaks and Klenow to detect both single- and double-strand DNA breaks has not been reported after TBI. Accordingly, coronal brain sections from naive rats and rats at 0, 0.5, 1, 2, 6, 24, and 72 h (n = 3-5/group) after controlled cortical impact with imposed secondary insult were processed using the PANT, Klenow, and TUNEL methods. Cells with DNA breaks were detected by PANT in the ipsilateral hemisphere as early as 0.5 h after injury and were maximal at 6 h (cortex = 66.3+/-15.8, dentate gyrus 58.6+/-12.8, CA1 = 15.8+/-5.9, CA3 = 12.8+/-4.2 cells/x 400 field, mean +/- SEM, all p < 0.05 versus naive). Cells with DNA breaks were detected by Klenow as early as 30 min and were maximal at 24 h (cortex = 56.3+/-14.3, dentate gyrus 78.0+/-16.7, CA1 = 25.8+/-4.7, CA3 = 29.3+/-15.1 cells/x 400 field, all p < 0.05 versus naive). Cells with DNA breaks were not detected by TUNEL until 2 h and were maximal at 24 h (cortex = 47.7+/-21.4, dentate gyrus 63.0+/-11.9, CA1 = 5.6+/-5.4, CA3 = 6.9+/-3.7 cells/x 400 field, cortex and dentate gyrus p < 0.05 versus naive). Dual-label immunofluorescence revealed that PANT-positive cells were predominately neurons. These data demonstrate that TBI results in extensive DNA damage, which includes both single- and double-strand breaks in injured cortex and hippocampus. The presence of multiple types of DNA breaks implicate several pathways in the evolution of DNA damage after TBI.

Animals↗