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At least 217 records · Page 12Linked to original sources
PubMed1988

A computer program to display codon changes caused by mutagenesis.

A FORTRAN program for displaying the correspondence between codon changes and different possible base changes is presented. Changes of both single bases and dimers are considered. The user can specify the mutagenesis spectrum. Additionally, the user can choose whether or not to consider single or double events in a codon and whether or not to consider the possibility that the change of two bases (a dimer) can overlap a codon boundary. Furthermore, a variety of ways may be chosen to display and summarize the codon changes that can result from the specified mutagenesis. A user-supplied sequence or the genetic code table can be analyzed.

Codon↗
PubMed2002

Odorant receptor expression defines functional units in the mouse olfactory system.

Odorant receptors (ORs) mediate the interaction of odorous compounds with olfactory sensory neurons (OSNs) and influence the guidance of OSN axons to synaptic targets in the olfactory bulb (OB). OSNs expressing the same OR send convergent axonal projections to defined glomeruli in the OB and are thought to share the same odorant response properties. This expectation of functional similarity has not been tested experimentally, because it has not been possible to determine reproducibly the response properties of OSNs that express defined ORs. Here, we applied calcium imaging to characterize the odorant response properties of single neurons from gene-targeted mice in which the green fluorescent protein is coexpressed with a particular OR. We show that the odorants acetophenone and benzaldehyde are agonists for the M71 OR and that M71-expressing neurons are functionally similar in their response properties across concentration. Replacing the M71 coding sequence with that of the rat I7 OR changes the stimulus response profiles of this genetically defined OSN population and concomitantly results in the formation of novel glomeruli in the OB. We further show that the mouse I7 OR imparts a particular response profile to OSNs regardless of the epithelial zone of expression. Our data provide evidence that ORs determine both odorant specificity and axonal convergence and thus direct functionally similar afferents to form particular glomeruli. They confirm and extend the notion that OR expression provides a molecular basis for the formation and arrangement of glomerular functional units.

Acetophenones↗
PubMed2006

The response of amino acid frequencies to directional mutation pressure in mitochondrial genome sequences is related to the physical properties of the amino acids and to the structure of the genetic code.

The frequencies of A, C, G, and T in mitochondrial DNA vary among species due to unequal rates of mutation between the bases. The frequencies of bases at fourfold degenerate sites respond directly to mutation pressure. At first and second positions, selection reduces the degree of frequency variation. Using a simple evolutionary model, we show that first position sites are less constrained by selection than second position sites and, therefore, that the frequencies of bases at first position are more responsive to mutation pressure than those at second position. We define a measure of distance between amino acids that is dependent on eight measured physical properties and a similarity measure that is the inverse of this distance. Columns 1, 2, 3, and 4 of the genetic code correspond to codons with U, C, A, and G in their second position, respectively. The similarity of amino acids in the four columns decreases systematically from column 1 to column 2 to column 3 to column 4. We then show that the responsiveness of first position bases to mutation pressure is dependent on the second position base and follows the same decreasing trend through the four columns. Again, this shows the correlation between physical properties and responsiveness. We determine a proximity measure for each amino acid, which is the average similarity between an amino acid and all others that are accessible via single point mutations in the mitochondrial genetic code structure. We also define a responsiveness for each amino acid, which measures how rapidly an amino acid frequency changes as a result of mutation pressure acting on the base frequencies. We show that there is a strong correlation between responsiveness and proximity, and that both these quantities are also correlated with the mutability of amino acids estimated from the mtREV substitution rate matrix. We also consider the variation of base frequencies between strands and between genes on a strand. These trends are consistent with the patterns expected from analysis of the variation among genomes.

Amino Acids↗
PubMed1995

Chou-Fasman conformational amino acid parameters and the genetic code.

It was found that the distribution of Chou-Fasman P alpha conformational parameters within the genetic code (arranged into the one-step mutation ring) may be described by a quite simple trigonometric function of mutational angle. The mutational angle is defined as k pi/32, where k is a number of codons count from i under consideration to k. The principal eight-codon periodicity defines the P alpha-genetic code correspondence, but the other perioditicies seem also to modulate the principal function. The eight-codon periodicity finds the explanation in the regular changes of third bases of successive codons. These changes appear in the order; C,U,A,G,G,A,U,C, assigning eight maxima and eight minima of P alpha curve. The experimental P alpha values fit well the dependence found, except proline, the amino acid which breaks the regular eight-codon P alpha periodicity. The analysis of dependence obtained suggest that, in agreement with the hypothesis of Jukes (1973), arginine CGR and AGR codons could be in an earlier genetic code used for coding of ornithine.

Amino Acids↗
PubMed1984

Repeats of base oligomers as the primordial coding sequences of the primeval earth and their vestiges in modern genes.

Three outstanding properties uniquely qualify repeats of base oligomers as the primordial coding sequences of all polypeptide chains. First, when compared with randomly generated base sequences in general, they are more likely to have long open reading frames. Second, periodical polypeptide chains specified by such repeats are more likely to assume either alpha-helical or beta-sheet secondary structures than are polypeptide chains of random sequence. Third, provided that the number of bases in the oligomeric unit is not a multiple of 3, these internally repetitious coding sequences are impervious to randomly sustained base substitutions, deletions, and insertions. This is because the recurring periodicity of their polypeptide chains is given by three consecutive copies of the oligomeric unit translated in three different reading frames. Accordingly, when one reading frame is open, the other two are automatically open as well, all three being capable of coding for polypeptide chains of identical periodicity. Under this circumstance, a frame shift due to the deletion or insertion of a number of bases that is not a multiple of 3 fails to alter the down-stream amino acid sequence, and even a base change causing premature chain-termination can silence only one of the three potential coding units. Newly arisen coding sequences in modern organisms are oligomeric repeats, and most of the older genes retain various vestiges of their original internal repetitions. Some of the genes (e.g., oncogenes) have even inherited the property of being impervious to randomly sustained base changes.

Animals↗
PubMed2006

Detecting natural selection on cis-regulatory DNA.

Changes in transcriptional regulation play an important role in the genetic basis for evolutionary change. Here I review a growing body of literature that seeks to determine the forces governing the non-coding regulatory sequences underlying these changes. I address the challenges present in studying natural selection without the familiar structure and regularity of protein-coding sequences, but show that most tests of neutrality that have been used for coding regions are applicable to non-coding regions, albeit with some caveats. While some experimental investment is necessary to identify heritable regulatory variation, the most basic inferences about selection require very little functional information. A growing body of research on cis-regulatory variation has uncovered all the forms of selection common to coding regions, in addition to novel forms of selection. An emerging pattern seems to be the ubiquity of local adaptation and balancing selection, possibly due to the greater freedom organisms have to fine-tune gene expression without changing protein function. It is clear from multiple single locus and whole genome studies of non-coding regulatory DNA that the effects of natural selection reach far beyond the start and stop codons.

Animals↗
PubMed2004

Mutational analysis of susceptibility genes RNASEL/HPC1, ELAC2/HPC2, and MSR1 in sporadic prostate cancer.

Three putative prostate cancer-susceptibility genes, RNASEL/HPC1 at 1q24, MSR1 at 8p22, and ELAC2/HPC2 at 17p11, have recently been identified. Our objective was to investigate somatic mutations in these genes in sporadic prostate cancer. We analyzed 39 clinical prostate cancer specimens, 10 prostate cancer xenografts (LuCaP series), and 4 prostate cancer cell lines (LNCaP, DU145, PC-3, and MPC-3) for genetic changes using denaturing high-performance liquid chromatography and direct sequencing in order to screen the whole coding regions of RNASEL and MSR1, as well as exons 7 and 17 of ELAC2. The known 471delAAAG truncating mutation was found in the RNASEL gene in cell line LNCaP. The only new missense variation in RNASEL, Gly296Val, was found in cell line DU145, but not in any other samples. RNASEL and ELAC2 also showed the common missense polymorphic changes. A previously reported truncating mutation (Arg293X) was found in MSR1 in the germ line of one individual. Our results indicate that inactivation of the RNASEL, ELAC2, or MSR1 genes by somatic mutation is a rare phenomenon in sporadic prostate cancer.

Animals↗
PubMed2004

The effect of species models on estimates of within-lineage variation in integration.

Species may be modeled as comprised of individuals, populations or a virtual code. A virtual code can be understood as general potential that appears as actualization within specific environmental, both internal and external, contexts. These general potentials form a capacity to network that allows potentials to be expressed and offers robustness through its interconnections. In the present work, the degree of within-lineage variation in integration was not strongly model-dependent. However, the relationships among model-dependent estimates of such variation and within-lineage phyletic variation were not equal. The strongest relationship was between within-lineage variation in integration, when species were modeled as a virtual code, and within-lineage phyletic variation. The second strongest, and only other statistically significant relationship, was between variation in integration when species were modeled as a virtual code and as a collection of populations. The last result argues for a strong ontogenetic and micro-environmental effect on the expression of features in an individual. If species were a virtual code they would evolve by incorporation of all attributes, ontogenetic, environmental and genetic into that code until it becomes unstable and bifurcates. Species as a virtual code, an approach that explicitly incorporates developmental change into evolution, is a non-material representation of species as a complex information system, incorporating, if we refer to mathematical analysis, both the real and the imaginary. If one wished to stress the material, this study could be seen as empirical documentation of species as information systems.

Biological Evolution↗
PubMed1990

Comparison of vaccine strains and the virus causing the 1986 foot-and-mouth disease outbreak in Spain: epizootiological analysis.

RNAs of the most recent foot-and-mouth disease virus isolated in Spain (A5Sp86) during the 1986 outbreak, and of the three vaccine strains in use at that time in that country, have been compared. Although these viruses are serologically indistinguishable, differences have been found among them by T1 fingerprinting. This genetic heterogeneity affects the immunogenic VP1 gene, with amino acid changes located at the carboxyterminal end of the molecule. VP1-coding sequences obtained have been compared with those previously reported for European A5 FMDVs and it has been possible to trace their phylogenetic origin. The most parsimonious evolutionary tree obtained shows that the viruses analyzed are closely related to those previously isolated in 1983 in Spain, Portugal and Morocco. In spite of the VP1 sequence homology shown by this group of viruses, the genetic distances among field isolates and vaccine strains are significantly shorter than the distances found among field isolates. Thus, a significant relationship among virus recovered from recent outbreaks and the vaccine strains in use at that time in Spain, has been obtained.

Amino Acid Sequence↗
PubMed1997

The HRX proto-oncogene product is widely expressed in human tissues and localizes to nuclear structures.

Chromosomal rearrangement of the HRX (MLL, ALL-1, Htrx) gene situated at chromosome band 11q23 is one of the most frequent genetic changes in infant leukemias of myeloid and lymphoid lineage and in treatment-induced secondary leukemias. The HRX gene codes for a predicted 431-kD protein that shows significant homology to the Drosophila trithorax protein, an Hox epigenetic regulator. Typically, the region encoding the HRX gene is rearranged, mostly in reciprocal translocations with a number of partners, resulting in a range of fusion genes. However, this is not the only abnormality affecting HRX because partial duplication of the gene, as well as interstitial deletions, can occur. Despite extensive studies of HRX at the genetic level, the protein products of the HRX gene and their patterns of expression in normal and leukemic cells remain uncharacterized. In this study we analyzed the distribution and localization of HRX proteins in cell lines and human tissues, using both polyclonal and monoclonal antibodies. The specificity of these reagents was confirmed using cells transfected with the HRX-ENL fusion gene. Western blot analyses of protein extracts from cells carrying the t(11;19) and t(4;11) translocations showed HRX chimeric proteins whose migrations corresponded to the sizes predicted from analyses of translocation-induced fusion mRNAs expressed by the derivative 11 chromosomes. Immunocytochemical analysis showed a punctate distribution of wild-type and chimeric HRX proteins within cell nuclei, suggesting that HRX localizes to nuclear structures in cells with and without 11q23 translocations. Nuclear staining was found in the majority of tissues studied with the strongest reactivity in cerebral cortex, kidney, thyroid, and lymphoid tissues. Thus, HRX is widely expressed in most cell types including hematopoietic cells, a finding that precludes an immunocytochemical approach for diagnosis of leukemias bearing 11q23 structural abnormalities.

Animals↗
PubMed1999

Isolation and characterization of a transfectant influenza B virus altered in RNA segment 6.

This report describes the successful generation of an influenza B transfectant virus altered in RNA segment 6, which encodes the neuraminidase (NA) protein. The procedure for selection of the transfectant virus relies on the use of strain-specific anti-NA monoclonal antibodies to inhibit growth of the helper virus within the system. A transfectant virus has been engineered which has a coding change in the NA protein. This change resulted in attenuated growth in vitro that could be rescued by addition of exogenous bacterial NA. The mutant virus-associated NA activity was unstable as a result of the engineered changes. The ability to genetically manipulate influenza B virus segment 6 will allow us to assess the function of both NA and the small protein NB, also coded from this RNA, within the context of the virus infectious cycle.

Influenza B virus↗
PubMed2005

[The effects of chronic hypobaric conditions: skeletal, muscular, and other phenotypic characteristics in high altitude dwellers].

Many studies have concentrated on investigating the effects of short and medium term hypobaric conditions in people living at low altitudes. In contrast, only little is known about long term or genetic adaptations to chronic hypobaric conditions in people living at high altitudes. A small number of phenotypic characteristics have been defined in these people so far, comprising hormonal functions, oxygen saturation of hemoglobin, skeletal growth, muscular morphology and function, cardiovascular functions, and fluid and electrolyte changes. Several of these characteristics have been attributed to genetic adaptations. However, so far, no specific genes coding for any of the specific phenotypes found in high altitude dwellers have been detected.

Adaptation, Physiological↗
PubMed2002

Mitochondrial DNA in metazoa: degree of freedom in a frozen event.

The mitochondrial genome (mtDNA), due to its peculiar features such as exclusive presence of orthologous genes, uniparental inheritance, lack of recombination, small size and constant gene content, certainly represents a major model system in studies on evolutionary genomics in metazoan. In 800 million years of evolution the gene content of metazoan mitochondrial genomes has remained practically frozen but several evolutionary processes have taken place. These processes, reviewed here, include rearrangements of gene order, changes in base composition and arising of compositional asymmetry between the two strands, variations in the genetic code and evolution of codon usage, lineage-specific nucleotide substitution rates and evolutionary patterns of mtDNA control regions.

Animals↗
PubMed2002

Alternative CUG codon usage (Ser for Leu) in Pichia farinosa and the effect of a mutated killer gene in Saccharomyces cerevisiae.

The halotolerant yeast Pichia farinosa KK1 strain produces a killer toxin termed SMKT (salt-mediated killer toxin). Mass spectrometry and Edman sequencing of peptides from the mature SMKT and secreted protoxin demonstrate that positions specified by the CUG codon contain unmodified serine (Ser) in P.farinosa. In order to express the authentic SMK1 product in Saccharomyces cerevisiae, which uses the universal genetic code, the three CUG codons corresponding to Ser87, Ser137 and Ser206 in the SMK1 gene were changed to universal Ser codons by site-directed mutagenesis. The expression of the modified SMK1 gene with universal Ser codons was lethal in S.cerevisiae, as well as that of the unmodified SMK1 gene with the CUG codons. The secretion of protoxin with the authentic amino acid sequence from the modified SMK1 was significantly increased, whereas the transcription level of SMK1 was not affected in the presence or absence of CUG codon. Our results provide the first in vivo evidence that non-universal decoding of CUG is used in a hemiascomycetous yeast, P.farinosa.

Amino Acid Substitution↗
PubMedDate not supplied

A hydrogen-harps model for intracellular communication and its implications for the second genetic code.

Hydrogen bonds (HB) in proteins and nucleic acids oscillate with frequencies of 10(11)-10(12) Hz, so giving rise to mm waves and far infrared emission. As HB undergo stretching and compression, their oscillation frequency will correspondingly change. The author (1989) 1b has devised a "musical" model, in which HB are compared to the strings of a string instrument: the harp. On the length, number and cooperation of "strings" (small and large hydrogen-harps) will depend the frequency, intensity and quality of "sound" (i.e. electromagnetic emission). Of course, this elementary hydrogen-harps model needs a physico-mathematical development. Nevertheless it can already be utilized to explain some essential moments of proteins and DNA function, on the base of its logical connection with Fröhlich's theory of coherent excitations. It might also help the understanding of the second genetic code mechanisms.

Cell Communication↗
PubMed1995

Multisite oligonucleotide-mediated mutagenesis: application to the conversion of a mitochondrial gene to universal genetic code.

Using multisite oligonucleotide-mediated mutagenesis in conjunction with a mutagenesis selection procedure and rapid screening by allele-specific oligonucleotide hybridization has allowed us to develop a reliable protocol that enables a large number of base changes to be introduced rapidly into a piece of DNA, with the minimum number of manipulations. We have applied this protocol to generate synthetic versions of four mouse mitochondrial genes capable of being expressed in the nucleus/cytosol.

Amino Acid Sequence↗
PubMed1998

Information Theory, Scaling Laws and the Thermodynamics of Evolution.

Renormalization symmetry and the Legendre transformation are imposed on a parametized form of ergodic source uncertainty, a widely-applied model for "languages" ranging from the spoken word to genetic codes. Using the Shannon-McMillan theorem to identify a duality between source uncertainty and free energy density, this procedure: (i) suggests that a punctuated "phase change" and resulting sudden fragmentation or coalescence should be the norm for "language"-based phenomena, particularly the transfer of "genetic" information within reproducing populations; (ii) gives a power law for that phase change near transition; (iii) provides a "disorder" construct similar to an entropy which may trigger higher degrees of punctuation in social systems than is suggested from simple physical analogs; and (iv) gives "equations of state" relating ensemble averages which should be observable within coalesced systems. The general formalism is explicitly applied to problems of speciation, coevolution and group selection, and comparison made with the work of Eigen and his associates.Copyright 1998 Academic Press Limited

Journal Article↗