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Showing papers on "Gene published in 1974"


Journal ArticleDOI
TL;DR: It is concluded that most of the variation in nuclear DNA mass in higher plant chromosomes can be accounted for by variation in repeated-sequence DNA.
Abstract: The reannealing kinetics of denatured DNA fragments from 23 species of higher plants have been studied, using hydroxylapatite chromatography to distinguish reannealed from single-stranded DNA. The 2C nuclear DNA contents of the species varied between 1.7 and 98 pg. The proportions of DNA in species with a nuclear DNA mass above 5 pg that reannealed with the kinetics of sequences present in more than 100 copies were high (69–92% with a mean of 80±2.0%). For species with less than 4 pg of DNA, the mean proportion of repeated-sequence DNA was 62±2.9%. It is concluded that most of the variation in nuclear DNA mass in higher plant chromosomes can be accounted for by variation in repeated-sequence DNA. The consequences of altering the adapted DNA content of a species by the addition of families of repeated sequences are discussed in relation to the proportion of repeated-sequence DNA.

555 citations


Journal ArticleDOI
01 May 1974-Genetics
TL;DR: Chemical analysis and a study of renaturation kinetics show that the nematode, Caenorhabditis elegans, has a haploid DNA content of 8 x 10(7) base pairs (20 times the genome of E. coli).
Abstract: Chemical analysis and a study of renaturation kinetics show that the nematode, Caenorhabditis elegans, has a haploid DNA content of 8 x 10(7) base pairs (20 times the genome of E. coli). Eighty-three percent of the DNA sequences are unique. The mean base composition is 36% GC; a small component, containing the rRNA cistrons, has a base composition of 51% GC. The haploid genome contains about 300 genes for 4S RNA, 110 for 5S RNA, and 55 for (18 + 28)S RNA.

552 citations


Journal ArticleDOI
11 Oct 1974-Nature
TL;DR: Evidence is presented that the mitochondrial genome is inherited maternally in mammals too, unlike chromosomal genes, which are inherited biparentally.
Abstract: EUKARYOTIC cells contain a class of cytoplasmic DNA molecules which are found only within the mitochondria, where they replicate and are transcribed (for a general review see ref. 1). This mitochondrial DNA (mtDNA) constitutes the ‘mitochondrial genome’ and carries genetic information essential to mitochondrial function. In view of its extranuclear location, it is not surprising that inheritance of the mitochondrial genome is not governed by the same rules that apply to chromosomal genes. For fungi2–7 and amphibians8 there is evidence that the mitochondrial genome of an individual is derived solely from the maternal parent (in contrast to chromosomal genes, which are inherited biparentally). We present here evidence that the mitochondrial genome is inherited maternally in mammals too.

508 citations


Journal ArticleDOI
TL;DR: The simplest of the three isolation procedures compared is shown to yield approximately two-thirds of the total mitochondrial DNA in the tissue culture cells examined and to yield at least four times the mitochondrial DNA mass per mitochondrial volume as HeLa cells.

496 citations


Journal ArticleDOI
TL;DR: Examination of the survival responses of multiple-mutant strains indicated a minimum of two pathways in the repair of X-ray damage, and a number of the mutants have been mapped and these were found to be dispersed over the genome.
Abstract: A set of 64 mutants of Saccharomyces cerevisiae that confer sensitivity to X-ray inactivation were analyzed genetically to determine the number of genetic loci involved. The mode of interaction of various combinations of mutants was also determined. A minimum of 17 genes, when mutant, increase X-ray sensitivity of yeast, primarily by eliminating the resistance of budding haploid cells and by removing the shoulder on the survival curves of diploid cells. Eight mutant loci affect principally X-ray sensitivity while the remaining genes also control sensitivity to ultraviolet. Some of the genes when homozygous block sporulation or result in partial or complete sterility. Examination of the survival responses of multiple-mutant strains indicated a minimum of two pathways in the repair of X-ray damage. A number of the mutants have been mapped and these were found to be dispersed over the genome.

469 citations


Journal ArticleDOI
01 Mar 1974-Science
TL;DR: It is apparent that, in addition to regulating the transcription of defined genome loci, the nonhistone chromosomal proteins include enzymes that have a general function, proteins that are involved in determining the structure of chromatin, as well as proteins that serve as recognition sites for binding of regulatory macromolecules.
Abstract: Evidence from several model systems suggests that nonhistone chromosomal proteins may regulate gene expression in eukaryotic cells. The data indicate that the synthesis of new species of nonhistone chromosomal proteins as well as modifications of preexisting nonhistone chromosomal proteins are involved in the control of transcription. However, from the vast number of proteins included in this class, it is apparent that, in addition to regulating the transcription of defined genome loci, the nonhistone chromosomal proteins include enzymes that have a general function, proteins that are involved in determining the structure of chromatin, as well as proteins that serve as recognition sites for binding of regulatory macromolecules. The presence of a nucleoplasmic pool of nonhistone chromosomal proteins which may exchange with the chromatin has also been reported (89). While it is clear that the nonhistone chromosomal proteins play a key role in the regulation of gene expression, the exact manner in which they interact with the genome to initiate, modify, or augment the transcription of specific RNA molecules remains to be resolved.

415 citations


Journal ArticleDOI
TL;DR: Experiments involving the shift of mutant cells from the restrictive to the permissive temperature in the presence of cycloheximide demonstrated that the protein synthesis requirement for yeast DNA replication can be completed before the cdc 7-mediated step.

357 citations


Journal ArticleDOI
TL;DR: A series of isonuclear cytoplasmic petite (ϱ−) mutants presenting various patterns of large deletions and retentions in the C321R — E514R region was used to study the functional organization of mitochondrial DNA.

225 citations


Journal ArticleDOI
06 Dec 1974-Nature
TL;DR: Endogenous viruses from primates are concluded to have infected and become part of the germ line of an evolutionary distant group, the ancestors of the domestic cat.
Abstract: Genes related to the nucleic acid of an endogenous domestic cat C-type virus (RD114) are found in the cellular DNA of anthropoid primates while many members of the cat family Felidae lack these sequences. Endogenous viruses from primates are thus concluded to have infected and become part of the germ line of an evolutionary distant group, the ancestors of the domestic cat.

203 citations


Journal ArticleDOI
TL;DR: A tentative map of the cytoplasmic RNA sequences has been constructed for viral RNA extracted from cells both early and late during infection, suggesting that RNA processing and selection may play a role in the regulation of viral mRNA production.
Abstract: The strands of the six EcoRI fragments and the HpaI fragments E and C of Ad2 DNA were separated by electrophoresis in agarose gels. Using 32P-labeled fragment strands in solution hybridization experiments, the fraction of each strand complementary to RNA extracted from infected or transformed cells was assayed by chromatography on hydroxylapatite. In this manner, a tentative map of the cytoplasmic RNA sequences has been constructed for viral RNA extracted from cells both early and late during infection (see Fig. 16; in the map shown, the two strands of Ad2 are named the r and l strands following the bacteriophage convention). Since early cytoplasmic RNA anneals to four distinct regions of the genome, Ad2 probably codes for at least four early gene functions. Summation experiments have shown that all RNA sequences found in the cytoplasm of cells early during infection are also present in the cells' cytoplasm at late times. Viral RNA sequences in five independently isolated and cloned transformed rat cell lines were also mapped on the Ad2 genome. One class of Ad2-transformed rat cells contains RNA sequences complementary to only the segment of Ad2 DNA from 0.03-0.10 on the physical map, and this corresponds to one of the four regions of the genome expressed early during infection. If a viral gene product is necessary to maintain the transformed phenotype of the cell or codes for the virus-specific tumor (T) antigen, this genetic information must be at the left end of the genome (see Fig. 16). The two other classes of Ad2-transformed rat cells contain viral RNA sequences complementary to two or three of the regions of the genome transcribed into early cytoplasmic RNA. At both early and late times during the lytic cycle, the nucleus of the infected cell contains viral RNA sequences that are not transported to the cell's cytoplasm, suggesting that RNA processing and selection may play a role in the regulation of viral mRNA production.

185 citations


Journal ArticleDOI
TL;DR: Derepression of genes on the inactive X-chromosome and of liver phenylalanine hydroxylase production are presented as possible examples of abnormal epigenetic changes that could be quantitatively studied by direct selection in vitro.
Abstract: In vitro enumeration of diploid human cell variants that are resistant to purine analogues is a possible method of detecting mutagenesis. Their incidences can be increased by the known mutagens, X-rays and N -methyl- N ′-nitro- N -nitrosoguanidine (MNNG). Usefulness of this method depends on the kinds of hereditary changes that confer analogue-resistance on somatic cells. If resistance usually results from changes in genetic material, in vitro studies could be useful indicators of mutagenic effects on somatic cells and germ cells in vivo . If epigenetic changes are primarily responsible for analogue-resistant variants, their enumeration might not provide information relevant to germinal mutations but would still be a useful way to detect induction of general kinds of stable phenotypic changes that could cause cancer. This article outlines hypothetical epigenetic and genetic causes of somatic cell variation and a prospective genetic analysis of human cell variants that are resistant to 8-azaguanine (AG) or 2,6-diaminopurine ( (DAP). Recent evidences and arguments favoring epigenetic origins of resistance to base-analogues are inconclusive. The often cited high rate of changes causing impermeability to BUdR in hamster cells is based on one improperly executed determination. Comparisons of rates of variation conferring BUdR-resistance on cultured haploid and diploid frog cells included diploid variants that did not behave as mutants and ignored major sources of error in estimating mutation rates. AG-resistance could result from recessive mutations in X-chromosomal genes but comparisons of rates of mutation in hamster cells of different ploidies did not provide information about the numbers of X-chromosomes in the variants. Reports that normal rodent HGPRT reappeared in hybrids of enzyme-deficient rodent cells and HGPRT-containing cells of other species or in the rodent cells alone in response to the conditions of cell hybridization did not include adequate controls for reversions in mutant genes of the rodent cells. Questions about the epigenetic and genetic origins of analogue-resistance are mostly unanswered. It remains possible that some kinds of abnormal epigenetic changes cause somatic disease. Specific methods for detecting their occurrence and responsiveness to environmental factors should be devised by focusing efforts on traits that are normally subject to epigenetic regulation. Derepression of genes on the inactive X-chromosome and of liver phenylalanine hydroxylase production are presented as possible examples of abnormal epigenetic changes that could be quantitatively studied by direct selection in vitro .

Journal ArticleDOI
TL;DR: Analysis of suitable DNA-DNA heteroduplex molecules in the electron microscope clearly shows one constitutive revertant of galOP::IS2-308 isolated on the F′8gal episome is due to fusion of the gal genes to IS2 located in the F-sequences.
Abstract: Genetic analysis of the constitutive revertants of the IS2 mutation 308 located in the control region of the gal operon on the bacterial chromosome suggests that the constitutive expression of the gal genes might be due to inversion of IS2.

Journal ArticleDOI
TL;DR: It is concluded that transcription initiated at p L by E. coli RNA polymerase is so modified by interaction with N protein that even distant nonsense codons are no longer read as a cause of polarity.

Journal ArticleDOI
20 Sep 1974-Nature
TL;DR: A system to study enzyme evolution experimentally and it is proposed that such mutations will be acceptable only in ‘silent’ gene copies—shown here to be a frequent response to selective pressure.
Abstract: A system to study enzyme evolution experimentally has been developed. Multiple mutations are required to improve enzyme specificity and the authors propose that such mutations will be acceptable only in ‘silent’ gene copies—shown here to be a frequent response to selective pressure.

Journal ArticleDOI
01 Jan 1974-Virology
TL;DR: The variability in length of the terminal repetition in any one phage is consistent with the interpretation that there is a variability of about 1% of the full molecular length in the amount of DNA packaged by the head-full mechanism.

Journal ArticleDOI
TL;DR: Covalently closed, circular, double-stranded DNA isolated from cells infected with bacteriophage f1 has been used as a template for coupled transcription and translation in vitro and it has been possible to identify six gene-specific polypeptides.

Journal ArticleDOI
01 Mar 1974-Virology
TL;DR: The genetic mapping of a locus of the Escherichia coli chromosome involved in the expression of the N gene function of phage λ suggests that the nus + allele is responsible for theexpression of a function necessary for N product activity.

Journal ArticleDOI
TL;DR: There is no widespread elimination of globin genes in non-erythroid somatic mouse tissues, and globin cDNA is a faithful, but partial, transcript of reticulocyte 9 S RNA, which contains both o and β globin messenger RNAs.

Journal ArticleDOI
TL;DR: It is assumed that the complex found in lysates of infected cells previously did exist as such inside the cells, but it is unable to exclude that it formed during or after lysis, and the results of pulse-chase radioactive labeling experiments on infected cells can be interpreted as showing that with time the single-stranded DNA leaves complex, presumably to be matured into virions, while the gene 5 proteins are re-used to form more complex.

Journal ArticleDOI
TL;DR: These studies demonstrate conclusively that polyploidization of the silk gland involves replication of all its genes to at least 4 × 105 times their concentration in a haploid sperm nucleus, probably by seventeen or more rounds of complete genome replication without cell division during larval development.

Journal ArticleDOI
TL;DR: It is suggested that in infections defective in late gene expression and consequently in the maturation of replicated DNA, the increased P32 production is caused by the large expansion of the DNA pool.

Journal ArticleDOI
TL;DR: It is concluded that the number of germ line genes is too small to account for the observed diversity of antibody molecules.
Abstract: RNA preparations containing 70-80% mouse κ-chain mRNA have been prepared. The remainder consists of many RNA species, each of which represents a small fraction of the total RNA. The κ-chain mRNA preparation hybridizes with mouse liver DNA with bi-phasic kinetics, indicating that it consists of two fractions —“unique” and “reiterated.” Competition hybridization experiments show that the homology among the unique fractions from different mRNAs is the same as the homology among the amino acid sequences of the corresponding κ-chains. Hence, in addition to the C-region (constant-region) sequences, (most of) the V-region (variable-region) sequences are also derived from unique germ line genes. The reiterated fractions from different κ-chain mRNAs show essentially complete homology with each other. This fraction seems to consist mostly of sequences which do not code for amino-acid sequences of the secreted polypeptide chain, i.e., the “external” section of the mRNA molecule. It is concluded that the number of germ line genes is too small to account for the observed diversity of antibody molecules.

Journal ArticleDOI
TL;DR: The hybridization data suggest that the gene for rRNA must be amplified during macronuclear formation with each sexual generation, and demonstrate that the multiple copies of a repeated gene in a somatic nucleus of a eukaryote can be generated from a small number of copies of that genes in a germinal nucleus.
Abstract: The percentage of DNA complementary to 25S and 17S rRNA has been determined for both the macro- and micronucleus of the ciliated protozoan, Tetrahymena pyriformis. Saturation levels obtained by DNA·RNA hybridization indicate that approximately 200 copies of the gene for rRNA per haploid genome were present in macronuclei. The saturation level obtained with DNA extracted from isolated micronuclei was only 5-10% of the level obtained with DNA from macronuclei. After correction for contamination of micronuclear DNA by DNA from macronuclei, only a few copies (possibly only 1) of the gene for rRNA are estimated to be present in micronuclei. Micronuclei are germinal nuclei. Macronuclei serve as somatic nuclei during vegetative growth but are destroyed every sexual generation and are reformed from products of meiosis, fertilization, and division of the micronuclei. Thus, the hybridization data suggest that the gene for rRNA must be amplified during macronuclear formation with each sexual generation. These observations also demonstrate that the multiple copies of a repeated gene in a somatic nucleus of a eukaryote can be generated from a small number of copies of that gene in a germinal nucleus.

Journal ArticleDOI
TL;DR: A series of mouse-human hybrids was prepared from mouse cells deficient in adenine phosphoribosyltransferase (EC 2.4.7) and normal human cells as mentioned in this paper.
Abstract: A series of mouse-human hybrids was prepared from mouse cells deficient in adenine phosphoribosyltransferase (EC 2.4.2.7) and normal human cells. The hybrids were made in medium containing adenine and alanosine, an antimetabolite known to inhibit de novo adenylic acid biosynthesis. The mouse cells, unable to utilize exogenous adenine, were killed in this medium, but the hybrids proliferated as a consequence of their retaining the human aprt gene. The hybrids were then exposed to the adenine analogs 2,6-diaminopurine and 2-fluoroadenine to select for cells that had lost this gene. Before exposure to the adenine analogs, the expression of human adenine phosphoribosyltransferase by the hybrids was strongly associated only with the presence of human chromosome 16, and afterwards this was the only human chromosome consistently lost. This observation suggests that the human aprt gene can be assigned to chromosome 16.

Journal ArticleDOI
01 Jan 1974-Virology
TL;DR: Crosses of line 100 or related inbred line 7 with other lines showed that the dominant I e gene did not block RAV-O production, but merely restricted its spread from cell to cell.

Journal ArticleDOI
18 Oct 1974-Nature
TL;DR: Results from this study have provided new information Regarding the functioning of the genes coding for the Leloir pathway enzymes in man1, and have revealed a relatively close and potentially useful linkage between the genes for galactokinase and for thymidine kinase.
Abstract: PROGRESS in somatic cell genetics now allows more rapid and precise localisation of genes within the human genome. A large number of mouse × human hybrid cell lines are available, permitting the investigator to choose, for phenotype assay, lines with a particular reduced human chromosome complement. An increasingly large number of hybrid lines carrying rearranged chromosomes are also becoming available for regional localisation studies. We have used such hybrid cell lines to assign a gene coding for galactokinase (EC 2.7.1.6) to human chromosome 17 and to further localise the gene to band 21–22 on the long arm of the chromosome. Results from this study have provided new information Regarding the functioning of the genes coding for the Leloir pathway enzymes in man1, and have revealed a relatively close and potentially useful linkage between the genes for galactokinase and for thymidine kinase (EC 2.7.1.21).

Journal ArticleDOI
01 Oct 1974-Virology
TL;DR: In this paper, the deletions were mapped genetically, making use of their effect on plaque morphology, and by electron microscopy of DNA heteroduplexes to T2, a T2 T4 hybrid, and T4 wild type.

Journal ArticleDOI
TL;DR: The size and nucleotide sequence complexity of the Bombyx mori genome has been determined from the kinetics of reassociation of its DNA and compares favorably with the DNA content of haploid B. mori spermatids and mature sperm determined cytophotometrically by Rasch (1973).
Abstract: The size and nucleotide sequence complexity of the Bombyx mori genome has been determined from the kinetics of reassociation of its DNA. Nonrepeated DNA comprises 55% of the genome, and the remainder is divided equally between sequences repeated roughly 500 and 50000 times. Non-repeated sequence DNA virtually free of repeated sequences was prepared by partial reassociation and subsequent fractionation on hydroxyapatite. The nucleotide sequence complexity of this component was determined relative to DNA from B. subtilis and E. coli. After correction for the size of the repeated sequence fraction, the DNA content of the Bombyx mori genome was calculated to be 0.53±0.02×10−12 g. This value compares favorably with the DNA content of haploid B. mori spermatids and mature sperm determined cytophotometrically by Rasch (1973).

Journal ArticleDOI
05 Jul 1974-Nature
TL;DR: A mutation which maps between genes 52 and t defines a new regulatory gene in IN T4 infections, and some of the properties of such a mutation are described.
Abstract: IN T4 infections the mechanisms determining the time and rates of expression of early genes are not yet clearly understood. Although mutants which do not make late gene products or which are defective in DNA synthesis generally fail to turn off the synthesis of most early gene products, no mutations have been described which affect either the time of appearance or the initial rate of synthesis of proteins from more than a single early gene. This preliminary report describes the isolation and some of the properties of such a mutation. This mutation which maps between genes 52 and t defines a new regulatory gene.

Journal ArticleDOI
TL;DR: Thermal melting profiles of the DNA:RNA and DNA:DNA hybrids suggest that the partial homology of the viral nucleic acid sequences is the result of base alterations throughout the viral genomes, rather than the loss of discrete segments of viral sequences.
Abstract: The nucleic acid sequence homology between various murine, endogenous type-C viruses (three host range classes of BALB/c virus, the AT-124 virus, and the CCL 52 virus) and two laboratory strains of murine leukemia virus (Rauscher and Kirsten) was determined by DNA:RNA hybridization. The viral sequences exhibit varying degrees of partial homology. DNA:DNA hybridizations were performed between [3H]DNA probes prepared from N- and X-tropic BALB/c endogenous viruses and cellular DNAs from BALB/c, NIH Swiss, and AKR inbred mouse strains as well as from California feral mice and the Asian mouse subspecies Mus musculus molossinus and M. musculus castaneus. All of these strains of mice are shown to possess multiple (six to seven per haploid genome), partially related copies of type-C virogenes in their DNAs. Thermal melting profiles of the DNA:RNA and DNA:DNA hybrids suggest that the partial homology of the viral nucleic acid sequences is the result of base alterations throughout the viral genomes, rather than the loss of discrete segments of viral sequences.