Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “Exons”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 37 records · Page 2
All sourcesNASA NTRSDOE OSTI
NASA NTRS2005

Identification of transcribed sequences in Arabidopsis thaliana by using high-resolution genome tiling arrays

Using a maskless photolithography method, we produced DNA oligonucleotide microarrays with probe sequences tiled throughout the genome of the plant Arabidopsis thaliana. RNA expression was determined for the complete nuclear, mitochondrial, and chloroplast genomes by tiling 5 million 36-mer probes. These probes were hybridized to labeled mRNA isolated from liquid grown T87 cells, an undifferentiated Arabidopsis cell culture line. Transcripts were detected from at least 60% of the nearly 26,330 annotated genes, which included 151 predicted genes that were not identified previously by a similar genome-wide hybridization study on four different cell lines. In comparison with previously published results with 25-mer tiling arrays produced by chromium masking-based photolithography technique, 36-mer oligonucleotide probes were found to be more useful in identifying intron-exon boundaries. Using two-dimensional HPLC tandem mass spectrometry, a small-scale proteomic analysis was performed with the same cells. A large amount of strongly hybridizing RNA was found in regions "antisense" to known genes. Similarity of antisense activities between the 25-mer and 36-mer data sets suggests that it is a reproducible and inherent property of the experiments. Transcription activities were also detected for many of the intergenic regions and the small RNAs, including tRNA, small nuclear RNA, small nucleolar RNA, and microRNA. Expression of tRNAs correlates with genome-wide amino acid usage.

Arabidopsis/genetics↗
NASA NTRS2003

Microsatellites in the Eukaryotic DNA Mismatch Repair Genes as Modulators of Evolutionary Mutation Rate

All "minor" components of the human DNA mismatch repair (MMR) system-MSH3, MSH6, PMS2, and the recently discovered MLH3-contain mononucleotide microsatellites in their coding sequences. This intriguing finding contrasts with the situation found in the major components of the DNA MMR system-MSH2 and MLH1-and, in fact, most human genes. Although eukaryotic genomes are rich in microsatellites, non-triplet microsatellites are rare in coding regions. The recurring presence of exonal mononucleotide repeat sequences within a single family of human genes would therefore be considered exceptional.

Chang, Dong Kyung↗
NASA NTRS1999

Antigen S1, encoded by the MIC1 gene, is characterized as an epitope of human CD59, enabling measurement of mutagen-induced intragenic deletions in the AL cell system

S1 cell membrane antigen is encoded by the MIC1 gene on human chromosome 11. This antigen has been widely used as a marker for studies in gene mapping or in analysis of mutagen-induced gene deletions/mutations, which utilized the human-hamster hybrid cell-line, AL-J1, carrying human chromosome 11. Evidence is presented here which identifies S1 as an epitope of CD59, a cell membrane complement inhibiting protein. E7.1 monoclonal antibody, specific for the S1 determinant, was found to react strongly with membrane CD59 in Western blotting, and to bind to purified, urinary form of CD59 in ELISAs. Cell membrane expression of S1 on various cell lines always correlated with that of CD59 when examined by immunofluorescent staining. In addition, E7.1 antibody inhibited the complement regulatory function of CD59. Identification of S1 protein as CD59 has increased the scope of the AL cell system by enabling analysis of intragenic mutations, and multiplex PCR analysis of mutated cells is described, showing variable loss of CD59 exons.

Non-NASA Center↗
NASA NTRS2000

Orthostatic intolerance and tachycardia associated with norepinephrine-transporter deficiency

BACKGROUND: Orthostatic intolerance is a syndrome characterized by lightheadedness, fatigue, altered mentation, and syncope and associated with postural tachycardia and plasma norepinephrine concentrations that are disproportionately high in relation to sympathetic outflow. We tested the hypothesis that impaired functioning of the norepinephrine transporter contributes to the pathophysiologic mechanism of orthostatic intolerance. METHODS: In a patient with orthostatic intolerance and her relatives, we measured postural blood pressure, heart rate, plasma catecholamines, and systemic norepinephrine spillover and clearance, and we sequenced the norepinephrine-transporter gene and evaluated its function. RESULTS: The patient had a high mean plasma norepinephrine concentration while standing, as compared with the mean (+/-SD) concentration in normal subjects (923 vs. 439+/-129 pg per milliliter [5.46 vs. 2.59+/-0.76 nmol per liter]), reduced systemic norepinephrine clearance (1.56 vs. 2.42+/-0.71 liters per minute), impairment in the increase in the plasma norepinephrine concentration after the administration of tyramine (12 vs. 56+/-63 pg per milliliter [0.07 vs. 0.33+/-0.37 pmol per liter]), and a disproportionate increase in the concentration of plasma norepinephrine relative to that of dihydroxyphenylglycol. Analysis of the norepinephrine-transporter gene revealed that the proband was heterozygous for a mutation in exon 9 (encoding a change from guanine to cytosine at position 237) that resulted in more than a 98 percent loss of function as compared with that of the wild-type gene. Impairment of synaptic norepinephrine clearance may result in a syndrome characterized by excessive sympathetic activation in response to physiologic stimuli. The mutant allele in the proband's family segregated with the postural heart rate and abnormal plasma catecholamine homeostasis. CONCLUSIONS: Genetic or acquired deficits in norepinephrine inactivation may underlie hyperadrenergic states that lead to orthostatic intolerance.

Non-NASA Center↗
NASA NTRS2000

Time- and dose-related interactions between glucocorticoid and cyclic adenosine 3',5'-monophosphate on CCAAT/enhancer-binding protein-dependent insulin-like growth factor I expression by osteoblasts

Glucocorticoid has complex effects on osteoblasts. Several of these changes appear to be related to steroid concentration, duration of exposure, or specific effects on growth factor expression or activity within bone. One important bone growth factor, insulin-like growth factor I (IGF-I), is induced in osteoblasts by hormones such as PGE2 that increase intracellular cAMP levels. In this way, PGE2 activates transcription factor CCAAT/enhancer-binding protein-delta (C/EBPdelta) and enhances its binding to a specific control element found in exon 1 in the IGF-I gene. Our current studies show that preexposure to glucocorticoid enhanced C/EBPdelta and C/EBPbeta expression by osteoblasts and thereby potentiated IGF-I gene promoter activation in response to PGE2. Importantly, this directly contrasts with inhibitory effects on IGF-I expression that result from sustained or pharmacologically high levels of glucocorticoid exposure. Consistent with the stimulatory effect of IGF-I on bone protein synthesis, pretreatment with glucocorticoid sensitized osteoblasts to PGE2, and in this context significantly enhanced new collagen and noncollagen protein synthesis. Therefore, pharmacological levels of glucocorticoid may reduce IGF-I expression by osteoblasts and cause osteopenic disease, whereas physiological transient increases in glucocorticoid may permit or amplify the effectiveness of hormones that regulate skeletal tissue integrity. These events appear to converge on the important role of C/EBPdelta and C/EBPbeta on IGF-I expression by osteoblasts.

NASA Program Biomedical Research and Countermeasur↗
NASA NTRS1999

Contractile function is unaltered in diaphragm from mice lacking calcium release channel isoform 3

Skeletal muscle expresses at least two isoforms of the calcium release channel in the sarcoplasmic reticulum (RyR1 and RyR3). Whereas the function of RyR1 is well defined, the physiological significance of RyR3 is unclear. Some authors have suggested that RyR3 participates in excitation-contraction coupling and that RyR3 may specifically confer resistance to fatigue. To test this hypothesis, we measured contractile function of diaphragm strips from adult RyR3-deficient mice (exon 2-targeted mutation) and their heterozygous and wild-type littermates. In unfatigued diaphragm, there were no differences in isometric contractile properties (twitch characteristics, force-frequency relationships, maximal force) among the three groups. Our fatigue protocol (30 Hz, 0.25 duty cycle, 37 degrees C) depressed force to 25% of the initial force; however, lack of RyR3 did not accelerate the decline in force production. The force-frequency relationship was shifted to higher frequencies and was depressed in fatigued diaphragm; lack of RyR3 did not exaggerate these changes. We therefore provide evidence that RyR3 deficiency does not alter contractile function of adult muscle before, during, or after fatigue.

Non-NASA Center↗
NASA NTRS1995

Structural characterization and regulatory element analysis of the heart isoform of cytochrome c oxidase VIa

In order to investigate the mechanism(s) governing the striated muscle-specific expression of cytochrome c oxidase VIaH we have characterized the murine gene and analyzed its transcriptional regulatory elements in skeletal myogenic cell lines. The gene is single copy, spans 689 base pairs (bp), and is comprised of three exons. The 5'-ends of transcripts from the gene are heterogeneous, but the most abundant transcript includes a 5'-untranslated region of 30 nucleotides. When fused to the luciferase reporter gene, the 3.5-kilobase 5'-flanking region of the gene directed the expression of the heterologous protein selectively in differentiated Sol8 cells and transgenic mice, recapitulating the pattern of expression of the endogenous gene. Deletion analysis identified a 300-bp fragment sufficient to direct the myotube-specific expression of luciferase in Sol8 cells. The region lacks an apparent TATA element, and sequence motifs predicted to bind NRF-1, NRF-2, ox-box, or PPAR factors known to regulate other nuclear genes encoding mitochondrial proteins are not evident. Mutational analysis, however, identified two cis-elements necessary for the high level expression of the reporter protein: a MEF2 consensus element at -90 to -81 bp and an E-box element at -147 to -142 bp. Additional E-box motifs at closely located positions were mutated without loss of transcriptional activity. The dependence of transcriptional activation of cytochrome c oxidase VIaH on cis-elements similar to those found in contractile protein genes suggests that the striated muscle-specific expression is coregulated by mechanisms that control the lineage-specific expression of several contractile and cytosolic proteins.

Non-NASA Center↗
NASA NTRS1995

Hair-cell counts and afferent innervation patterns in the cristae ampullares of the squirrel monkey with a comparison to the chinchilla

1. The numbers of type I and type II hair cells were estimated by dissector techniques applied to semithin, stained sections of the horizontal, superior, and posterior cristae in the squirrel monkey and the chinchilla. 2. The crista in each species was divided into concentrically arranged central, intermediate, and peripheral zones of equal areas. The three zones can be distinguished by the sizes of individual hair cells and calyx endings, by the density of hair cells, and by the relative frequency of calyx endings innervating single or multiple type I hair cells. 3. In the monkey crista, type I hair cells outnumber type II hair cells by a ratio of almost 3:1. The ratio decreases from 4-5:1 in the central and intermediate zones to under 2:1 in the peripheral zone. For the chinchilla, the ratio is near 1:1 for the entire crista and decreases only slightly between the central and peripheral zones. 4. Nerve fibers supplying the cristae in the squirrel monkey were labeled by extracellular injections of horseradish peroxidase (HRP) into the vestibular nerve. Peripheral terminations of individual fibers were reconstructed and related to the zones of the cristae they innervated and to the sizes of their parent axons. Results were similar for the horizontal, superior, and posterior cristae. 5. Axons seldom bifurcate below the neuroepithelium. Most fibers begin branching shortly after crossing the basement membrane. Their terminal arbors are compact, usually extending no more than 50-100 microns from the parent exon. A small number of long intraepithelial fibers enter the intermediate and peripheral zones of the cristae near its base, then run unbranched for long distances through the neuroepithelium to reach the central zone. 6. There are three classes of afferent fibers innervating the monkey crista. Calyx fibers terminate exclusively on type I hair cells, and bouton fibers end only on type II hair cells. Dimorphic fibers provide a mixed innervation, including calyx endings to type I hair cells and bouton endings to type II hair cells. Long intraepithelial fibers are calyx and dimorphic units, whose terminal fields are similar to those of other fibers. The central zone is innervated by calyx and dimorphic fibers; the peripheral zone, by bouton and dimorphic fibers; and the intermediate zone, by all three kinds of fibers. Internal (axon) diameters are largest for calyx fibers and smallest for bouton fibers. Of the entire sample of 286 labeled fibers, 52% were dimorphic units, 40% were calyx units, and 8% were bouton units.(ABSTRACT TRUNCATED AT 400 WORDS).

Non-NASA Center↗
NASA NTRS2005

Genome-wide transcriptional analysis of flagellar regeneration in Chlamydomonas reinhardtii identifies orthologs of ciliary disease genes

The important role that cilia and flagella play in human disease creates an urgent need to identify genes involved in ciliary assembly and function. The strong and specific induction of flagellar-coding genes during flagellar regeneration in Chlamydomonas reinhardtii suggests that transcriptional profiling of such cells would reveal new flagella-related genes. We have conducted a genome-wide analysis of RNA transcript levels during flagellar regeneration in Chlamydomonas by using maskless photolithography method-produced DNA oligonucleotide microarrays with unique probe sequences for all exons of the 19,803 predicted genes. This analysis represents previously uncharacterized whole-genome transcriptional activity profiling study in this important model organism. Analysis of strongly induced genes reveals a large set of known flagellar components and also identifies a number of important disease-related proteins as being involved with cilia and flagella, including the zebrafish polycystic kidney genes Qilin, Reptin, and Pontin, as well as the testis-expressed tubby-like protein TULP2.

Polycystic Kidney Diseases/genetics↗
NASA NTRSDate not supplied

A Dominant Arabidopsis Thaliana ACTIN7 Mutant for Studies of Cytoskeletal-Mediated Root Gravity and Spaceflight Stress Responses

A forward genetic screen for Arabidopsis thaliana mutants that exhibited differential sensitivity to the actin-disrupting compound, latrunculin B (LatB), was conducted to uncover new players involved in actin-mediated root gravity responses. This to the isolation of a mutant that exhibited robust primary root growth at 100 nM LatB, which is a concentration that severely inhibits wild-type root elongation. Phenotypic analysis revealed that hypocotyl elongation in the dark and root hair tip growth in the mutant could tolerate LatB concentrations that impaired these processes in wild type. A cross between the mutant and wild type resulted in progeny resistance to LatB, which indicated that the mutant is dominant (hereafter referred to as LBR1 for LatB Resistant1). Filamentous-actin (F-actin) organization in LBR1 primary roots remained intact at 100 nM LatB, while that of wild type exhibited fragmented F-actin. Next generation sequencing revealed that LBR1 had a single nucleotide polymorphism (SNP) in the AT5G09810 gene that changed cytosine to a thiamine at the first exon. AT5G09810 encodes ACTIN7 (ACT7), which is one of three vegetative actin isoforms in A. thaliana. The SNP in the ACT7 gene led to a change in a single amino acid from proline at position 32 to a serine. Transgenic complementation of LBR1 plants with wild-type ACT7 under the control of the ACT7 promoter (pACT7:ACT7) and wild-type plants with LBR1, which contained the proline to serine mutation, also under the ACT7 promoter (pACT7:LBR1) confirmed that LBR1 is ACT7. The pACT7:LBR1 construct was also able to confer LatB resistance to the act7-5 and act2-3 vegetative ACT mutants. Moreover, LBR1 exhibited partial tolerance to salt and low phosphate, and enhanced root skewing on a clinostat, suggesting that site-directed engineering of vegetative ACT presents a strategy for generating stress-tolerant plants for spaceflight applications and studies of actin-mediated gravity responses.

Plant Space Biology↗
NASA NTRSDate not supplied

MULTI-OMICS STUDY OF THE EFFECT OF REDOX-ACTIVE METALLOPORPHYRIN ON MURINE RETINA DURING SPACEFLIGHT

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Biostatistics↗
NASA NTRSDate not supplied

A Dominant Arabidopsis Thaliana ACTIN7 Mutant for Studies of Cytoskeletal-Mediated Root Gravity and Spaceflight Stress Responses

A forward genetic screen for Arabidopsis thaliana mutants that exhibited differential sensitivity to the actin-disrupting compound, latrunculin B (LatB), was conducted to uncover new players involved in actin-mediated root gravity responses. This led to the isolation of a mutant that exhibited robust primary root growth at 100 nM LatB, which is a concentration that severely inhibits wild-type root elongation. Phenotypic analysis revealed that hypocotyl elongation in the dark and root hair tip growth in the mutant could tolerate LatB concentrations that impaired these processes in wild type. A cross between the mutant and wild type resulted in progeny resistance to LatB, which indicated that the mutant is dominant (hereafter referred to as LBR1 for LatB Resistant1). Filamentous-actin (F-actin) organization in LBR1 primary roots remained intact at 100 nM LatB, while that of wild type exhibited fragmented F-actin. Next generation sequencing revealed that LBR1 had a single nucleotide polymorphism (SNP) in the AT5G09810 gene that changed cytosine to a thiamine at the first exon. AT5G09810 encodes ACTIN7 (ACT7), which is one of three vegetative actin isoforms in A. thaliana. The SNP in the ACT7 gene led to a change in a single amino acid from proline at position 32 to a serine. Transgenic complementation of LBR1 plants with wild-type ACT7 under the control of the ACT7 promoter (pACT7:ACT7) and wild-type plants with LBR1, which contained the proline to serine mutation, also under the ACT7 promoter (pACT7:LBR1) confirmed that LBR1 is ACT7. The pACT7:LBR1 construct was also able to confer LatB resistance to the act7-5 and act2-3 vegetative ACT mutants. Moreover, LBR1 exhibited partial tolerance to salt and low phosphate, and enhanced root skewing on a clinostat, suggesting that site-directed engineering of vegetative ACT presents a strategy for generating stress-tolerant plants for spaceflight applications and studies of actin-mediated gravity responses.

Plant Space Biology↗
NASA NTRS2024

Multi-Omics Study of the Effect of Redox-Active Metalloporphyrin on Murine Retina During Spaceflight

Astronauts returning from spaceflight have experienced eye problems, which may decrease retinal performance and lead to long-term effects on visual acuity. This study leverages the collected data from spaceflown murine retinas that were treated with redox-active metalloporphyrin (BuOE) to mitigate spaceflight-induced changes and respective ground controls. 10-week-old adult C57BL/6 male mice (n=5 in each of BuOE treated and saline control groups for spaceflown and ground control samples) were flown on Space-X 24 to the ISS national lab, kept in low earth orbit for 35 days and returned to Earth alive. Our multi-omics analysis of RNA-sequencing and reduced representation bisulfite sequencing (RRBS) data generated from subsequent murine retina tissues uncovered genes, pathways, and epigenetic modifications consistent with therapeutic potential of BuOE. From RNA-Seq analysis of spaceflown murine samples, the treatment group show differentially expressed genes relative to saline controls that reached significance (adjusted p-value < 0.05) and included genes Gpx3 and Crhbp, which are related to protection against cell oxidative damage and cellular response to organonitrogen compounds. Ranked fold-changes from the same contrast were used for gene set enrichment analysis, which showed biological processes reaching significance (adjusted p-value < 0.05) including glutathione metabolic processes and cellular response to xenobiotic stimulus. RRBS data of the spaceflown murine samples found 139 hyper or hypo differentially methylated sites spread across chromosomes 1-19 (20% promoters, 21% exons, 43% introns | 20 CpG islands, 7 CpG shores) with a 10% methylation difference (q-value < 0.05).The findings from this investigation have the potential to provide valuable insights into the molecular mechanisms underlying conditions like spaceflight associated neuro-ocular syndrome and assess the effectiveness of BuOE as a countermeasure for astronauts experiencing neuro-ophthalmic abnormalities, which can lead to long-term effects on visual acuity.

Biostatistics↗
NASA NTRS1995

Statistical and linguistic features of DNA sequences

We present evidence supporting the idea that the DNA sequence in genes containing noncoding regions is correlated, and that the correlation is remarkably long range--indeed, base pairs thousands of base pairs distant are correlated. We do not find such a long-range correlation in the coding regions of the gene. We resolve the problem of the "non-stationary" feature of the sequence of base pairs by applying a new algorithm called Detrended Fluctuation Analysis (DFA). We address the claim of Voss that there is no difference in the statistical properties of coding and noncoding regions of DNA by systematically applying the DFA algorithm, as well as standard FFT analysis, to all eukaryotic DNA sequences (33 301 coding and 29 453 noncoding) in the entire GenBank database. We describe a simple model to account for the presence of long-range power-law correlations which is based upon a generalization of the classic Levy walk. Finally, we describe briefly some recent work showing that the noncoding sequences have certain statistical features in common with natural languages. Specifically, we adapt to DNA the Zipf approach to analyzing linguistic texts, and the Shannon approach to quantifying the "redundancy" of a linguistic text in terms of a measurable entropy function. We suggest that noncoding regions in plants and invertebrates may display a smaller entropy and larger redundancy than coding regions, further supporting the possibility that noncoding regions of DNA may carry biological information.

Non-NASA Center↗
NASA NTRS2001

Analysis of the myosins encoded in the recently completed Arabidopsis thaliana genome sequence

BACKGROUND: Three types of molecular motors play an important role in the organization, dynamics and transport processes associated with the cytoskeleton. The myosin family of molecular motors move cargo on actin filaments, whereas kinesin and dynein motors move cargo along microtubules. These motors have been highly characterized in non-plant systems and information is becoming available about plant motors. The actin cytoskeleton in plants has been shown to be involved in processes such as transportation, signaling, cell division, cytoplasmic streaming and morphogenesis. The role of myosin in these processes has been established in a few cases but many questions remain to be answered about the number, types and roles of myosins in plants. RESULTS: Using the motor domain of an Arabidopsis myosin we identified 17 myosin sequences in the Arabidopsis genome. Phylogenetic analysis of the Arabidopsis myosins with non-plant and plant myosins revealed that all the Arabidopsis myosins and other plant myosins fall into two groups - class VIII and class XI. These groups contain exclusively plant or algal myosins with no animal or fungal myosins. Exon/intron data suggest that the myosins are highly conserved and that some may be a result of gene duplication. CONCLUSIONS: Plant myosins are unlike myosins from any other organisms except algae. As a percentage of the total gene number, the number of myosins is small overall in Arabidopsis compared with the other sequenced eukaryotic genomes. There are, however, a large number of class XI myosins. The function of each myosin has yet to be determined.

NASA Discipline Plant Biology↗
NASA NTRS1995

Systematic analysis of coding and noncoding DNA sequences using methods of statistical linguistics

We compare the statistical properties of coding and noncoding regions in eukaryotic and viral DNA sequences by adapting two tests developed for the analysis of natural languages and symbolic sequences. The data set comprises all 30 sequences of length above 50 000 base pairs in GenBank Release No. 81.0, as well as the recently published sequences of C. elegans chromosome III (2.2 Mbp) and yeast chromosome XI (661 Kbp). We find that for the three chromosomes we studied the statistical properties of noncoding regions appear to be closer to those observed in natural languages than those of coding regions. In particular, (i) a n-tuple Zipf analysis of noncoding regions reveals a regime close to power-law behavior while the coding regions show logarithmic behavior over a wide interval, while (ii) an n-gram entropy measurement shows that the noncoding regions have a lower n-gram entropy (and hence a larger "n-gram redundancy") than the coding regions. In contrast to the three chromosomes, we find that for vertebrates such as primates and rodents and for viral DNA, the difference between the statistical properties of coding and noncoding regions is not pronounced and therefore the results of the analyses of the investigated sequences are less conclusive. After noting the intrinsic limitations of the n-gram redundancy analysis, we also briefly discuss the failure of the zeroth- and first-order Markovian models or simple nucleotide repeats to account fully for these "linguistic" features of DNA. Finally, we emphasize that our results by no means prove the existence of a "language" in noncoding DNA.

NASA Discipline Number 14-10↗
NASA NTRS1995

Long-range correlation properties of coding and noncoding DNA sequences: GenBank analysis

An open question in computational molecular biology is whether long-range correlations are present in both coding and noncoding DNA or only in the latter. To answer this question, we consider all 33301 coding and all 29453 noncoding eukaryotic sequences--each of length larger than 512 base pairs (bp)--in the present release of the GenBank to dtermine whether there is any statistically significant distinction in their long-range correlation properties. Standard fast Fourier transform (FFT) analysis indicates that coding sequences have practically no correlations in the range from 10 bp to 100 bp (spectral exponent beta=0.00 +/- 0.04, where the uncertainty is two standard deviations). In contrast, for noncoding sequences, the average value of the spectral exponent beta is positive (0.16 +/- 0.05) which unambiguously shows the presence of long-range correlations. We also separately analyze the 874 coding and the 1157 noncoding sequences that have more than 4096 bp and find a larger region of power-law behavior. We calculate the probability that these two data sets (coding and noncoding) were drawn from the same distribution and we find that it is less than 10(-10). We obtain independent confirmation of these findings using the method of detrended fluctuation analysis (DFA), which is designed to treat sequences with statistical heterogeneity, such as DNA's known mosaic structure ("patchiness") arising from the nonstationarity of nucleotide concentration. The near-perfect agreement between the two independent analysis methods, FFT and DFA, increases the confidence in the reliability of our conclusion.

Non-NASA Center↗
NASA NTRS1994

Mosaic organization of DNA nucleotides

Long-range power-law correlations have been reported recently for DNA sequences containing noncoding regions. We address the question of whether such correlations may be a trivial consequence of the known mosaic structure ("patchiness") of DNA. We analyze two classes of controls consisting of patchy nucleotide sequences generated by different algorithms--one without and one with long-range power-law correlations. Although both types of sequences are highly heterogenous, they are quantitatively distinguishable by an alternative fluctuation analysis method that differentiates local patchiness from long-range correlations. Application of this analysis to selected DNA sequences demonstrates that patchiness is not sufficient to account for long-range correlation properties.

NASA Discipline Number 14-10↗