Showing papers on "Gene published in 1975"
2,758 citations
TL;DR: This article suggests mechanisms that may account for the differentiated state of dividing or nondividing cells and that also attempt to explain the ordered switching on or off of genes during development.
Abstract: It is generally accepted that the differentiated state of a given type of cell is associated with the activity of a particular set of genes, together with the total inactivity of those sets associated with the differentiation of other cell types. It is also clear that the differentiated state of dividing or nondividing cells is often extremely stable. In this article we suggest mechanisms that may account for this stability and that also attempt to explain the ordered switching on or off of genes during development. The phenotype of the organism depends on the genotype, and the genetic contribution from both parents is in almost all cases equal. Since the ultimate control of development resides in the genetic material, the actual program must be written in base sequences in the DNA. It is also clear that cytoplasmic components can have a powerful or overriding influence on genomic activity in particular cells, yet these cytoplasmic components are, of course, usually derived from the activity of genes at some earlier stage in development. A continual interaction between cytoplasmic enzymes and DNA sequences is an essential part of the model to be presented. Modification Enzymes In bacteria, enzymes exist which modify DNA by methylating adenine in the 6-position ( 1 ). These enzymes are extremely specific in their action; they modify bases at particular positions in short defined sequences of DNA, which, at least in some instances, form a palindrome. (A palindrome in DNA is an inverted duplication, with twofold rotational symmetry. The 3′ →...
1,708 citations
TL;DR: This chapter discusses the immune response region, the genes of which appear to control a variety of immune phenomena—including antibody response to many antigens, susceptibility to tumor viruses, and graft-versus-host (GVH), and mixed lymphocyte culture (MLC) reactions.
Abstract: Publisher Summary One of the most rapidly developing areas of immunologic research deals with the H-2 gene complex, a tightly linked series of genes controlling a variety of immunologic traits, including histocompatibility and immune responsiveness. This chapter summarizes the varieties of phenotypic traits associated with differences in the H-2 complex. The mapping of the H-2 complex into four major regions marked by H-2K, Ir-1, Ss-Slp, and H-2D genes plus the associated Tla gene is discussed in the chapter, along with the phenotypic traits associated with these regions. The chapter discusses the immune response region, the genes of which appear to control a variety of immune phenomena—including antibody response to many antigens, susceptibility to tumor viruses, and graft-versus-host (GVH), and mixed lymphocyte culture (MLC) reactions. The H-2 complex consists of many genes with diverse functions, most of which control cell membrane structures and/or processes. The fact that lymphocytes are particularly affected by H-2 genes has important implications for immunology. However, some of the genes also affect other cell types, implying a still larger role for the H-2 complex, perhaps in development or in cell regulation. Because the H-2 complex is the most thoroughly characterized segment of a mammalian chromosome, it is also an important model for the studies of gene action, organization, and evolution in mammals.
737 citations
530 citations
TL;DR: Identification of mutant variants of the sequence combined with the in vitro biochemical studies of others has allowed us to tentatively identify the recognition site for each of these proteins, and to suggest how CAP might act at a distance to affect the interaction of RNA polymerase with the promoter.
Abstract: The nucleotide sequence of the lac promoter-operator region has been determined. The 122 base pairs comprising this region include the recognition sites for RNA polymerase, the positive regulatory protein, CAP, and the negative regulatory protein, the repressor. Identification of mutant variants of the sequence combined with the in vitro biochemical studies of others has allowed us to tentatively identify the recognition site for each of these proteins, and to suggest how CAP might act at a distance to affect the interaction of RNA polymerase with the promoter.
480 citations
TL;DR: It is suggested that the transformation process may require two distinct events, each related to A gene expression, which depended both on the nature of the A mutation in a given cell species and on the species of the cell transformed by a given mutant.
Abstract: In productive infection by simian virus 40, the A gene is known to regulate the initiation of viral DNA replication and to control the synthesis of late viral RNA. The function of the A gene in transforming infection was investigated by the infection of a variety of cell species with six independently isolated temperature-sensitive mutants belonging to the A complementation group. The A mutants failed to initiate the stable transformation of cells during continuous infection at the restrictive temperature. After the establishment of transformation at the permissive temperature and a subsequent shift to the restrictive temperature to block the A function, however, two distinct virus-cell interactions were identified. In one case, the increased colony-forming capacity of transformed cells remained stable after the temperature shift. In the other case, the temperature shift decreased the capacity of transformed cells to form colonies to the level of untransformed control cells. The outcome of the virus-cell interaction depended both on the nature of the A mutation in a given cell species and on the species of the cell transformed by a given mutant. These findings suggest that the transformation process may require two distinct events, each related to A gene expression.
403 citations
TL;DR: The properties of the lambdakan phage suggest that R factors contain systems capable of mediating genetic exchange in the absence of extensive DNA homology, and it is suggested that such systems of exchange may have played important roles in R factor evolution.
Abstract: Transpositions of segments of R factor (antibiotic resistance plasmids) to bacteriophage lambda have been selected and characterized Cells of Escherichia coli harboring R factors that determine kanamycin resistance were infected with phage lambda, and lambdakan transducing lines were obtained Each of the three examined is unusual when compared to lambda transducing phages containing E coli chromosomal genes: the kan insertions (a) occur at several sites, each well removed from the integration region POP', (b) are not associated with deletion of lambda phage DNA, and (c) are separable from the lambda genome during transduction or during lytic growth Two insertions from the same R factor contain 15 kilobase sequences repeated in inverted order The properties of the lambdakan phage suggest that R factors contain systems capable of mediating genetic exchange in the absence of extensive DNA homology It is suggested that such systems of exchange may have played important roles in R factor evolution
352 citations
TL;DR: It is advanced that a diploid species has two differing systems of genetic variability, and speciation may occur as selection operates on the perturbed genetic system to organize new coadapted closed systems which come to characterize the new species.
Abstract: A hypothesis is advanced that a diploid species has two differing systems of genetic variability. The "open" system consists of polymorphic gene loci which recombine freely without drastic effects on viability. Examples are electrophoretic, polygenic, clinal, and subspecific variability. The "closed" system consists of blocks of genes forming coadapted, internally balanced gene complexes with or without the presence of inversions as a stabilizing mechanism. Perturbation of these blocks (supergenes) by crossing over results in greatly reduced viability under normal natural selection. These blocks vary between but not within species. When natural selection is relaxed, as during a populational flush-crash-founder cycle, the coadaptive balances of the closed system may become disorganized and one or more discordant individuals may survive. Speciation may occur as selection operates on the perturbed genetic system to organize new coadapted closed systems which come to characterize the new species.
343 citations
TL;DR: Thirty-five temperature-sensitive mutants of Aspergillus nidulans which are defective in nuclear division, septation or distribution of nuclei along the mycelium have been isolated, and most have been subjected to complementation analysis and mapped to chromosome.
Abstract: Forty-five temperature-sensitive mutants of Aspergillus nidulans which are defective in nuclear division, septation or distribution of nuclei along the mycelium have been isolated, and most have been subjected to complementation analysis and mapped to chromosome. Thirty-five of the mutants were unable to complete nuclear division at the restrictive temperature. Twenty-six of these mutants exhibited a co-ordinate drop in both spindle and chromosome mitotic indices at 42 °C, indicating that they fail to enter mitosis. These mutants have been assigned to the gene symbol nim. Nine mutants exhibited a co-ordinate rise in spindle and chromosome mitotic indices at 42 °C, indicating that they are arrested in mitosis. These mutants were assigned the gene symbol bim. Five mutants failed to form septa and were given the gene symbol sep; and five mutants had an abnormal nuclear distribution and were given the gene symbol nud. All of the mutations were recessive. Most of the mutants were in different complementation groups. Mutants in the same complementation groups were phenotypically similar, but phenotypically similar mutants were not necessarily or usually in the same complementation group. There was no evidence for genetic clustering of phenotypically similar mutants. The mutants were located on all eight chromosomes.
305 citations
TL;DR: Genetic studies show that Escherichia coli has three enzymes capable of phosphorylating glucose: soluble adenosine 5'-triphosphate-dependent glucokinase, which plays only a minor role in glucose metabolism; an enzyme II with high specificity for the D-glucose configuration; and another enzyme II, called mannosephosphotransferase, with broader specificity.
Abstract: Genetic studies show that Escherichia coli has three enzymes capable of phosphorylating glucose: soluble adenosine 5'-triphosphate-dependent glucokinase, which plays only a minor role in glucose metabolism; an enzyme II, called glucosephosphotransferase, with high specificity for the D-glucose configuration; and another enzyme II, called mannosephosphotransferase, with broader specificity. The former enzyme II is active on glucose and methyl-alpha-glucopyranoside, whereas the latter is active on D-glucose, D-mannose, 2-deoxy-D-glucose, D-glucosamine, and D-mannosamine. Mutations leading to loss of glucosephosphotransferase activity and designated by the symbol gpt are between the purB and pyrC markers in a locus previously called cat. The locus of mutations to loss of mannosephosphotransferase, mpt, is between the eda and fadD genes. Mutations to loss of glucokinase, glk, are between the ptsI and dsd genes.
289 citations
TL;DR: The results show that chromosomal evolution has been faster in placental mammals than in other vertebrates or molluscs, consistent with published evidence that placentals have also been evolving unusually fast in anatomy and way of life.
Abstract: To test the hypothesis that the evolution of organisms is dependent to a large degree on gene rearrangement, we devised a way of estimating rates of evolutionary change in karyotype. This non-biochemical method is based on consideration of chromosomal variability within taxonomic groups having a fossil record. The results show that chromosomal evolution has been faster in placental mammals than in other vertebrates or molluscs. This finding is consistent with published evidence that placentals have also been evolving unusually fast in anatomy and way of life. However, the structural genes of placentals seem not to have experienced accelerated evolution. Possibly, therefore, anatomical evolution may be facilitated by gene rearrangement. To explain how placentals achieved this rate of chromosomal evolution, we consider the process by which a new gene arrangement becomes fixed and spreads. The structure and dynamics of placental populations may be especially favorable for this process. The key factor involved seems to be the type of social behavior which produces small effective population sizes and inbreeding. As Bush points out elsewhere, such social structuring of populations may promote rapid fixation of gene rearrangements and rapid speciation.
TL;DR: Two copies of the structural gene for the elongation factor EF-Tu have been identified in Escherichia coli: one near rif and the other near str.
Abstract: Two copies of the structural gene for the elongation factor EF-Tu have been identified in Escherichia coli: one near rif and the other near str. The latter seems to belong to a single transcriptional unit together with the genes for ribosomal protein S7, S12 (str) and the elongation factor EF-G (fus).
TL;DR: The results of this study provide compelling evidence for the existence of the gene or genes controlling optimal T-B-cell cooperative interactions in the designated I region of the H-2 gene complex.
Abstract: The results of this study provide compelling evidence for the existence of the gene or genes controlling optimal T-B-cell cooperative interactions in the designated I region of the H-2 gene complex. Previously, we have speculated that the relevant gene(s) involved may well be located in this region based on several observations from our earlier work in this area (3, 5, 6). Thus, in the preceding paper, we showed that T and B cells from B10.BR and A strain mice developed effective cooperative interactions in vitro to DNP-KLH in a system identical to the one reported herein. Since these mice differ for genes in the S and D regions of H-2 but are identical for K and I region genes, we were able to localize the critical genes to the K-end of H-2.
TL;DR: It is now apparent that steroids induce de novo synthesis of both messenger RNA (mRNA) and ribosomal RNA (rRNA); the role of the former in directing the synthesis of specific proteins is reasonably clear but that of the latter remains to be elucidated.
TL;DR: Recent analyses of the sequence components present in hnRNA and mRNA are discussed and how they may be related to each other and to the organization of the genome.
01 Jan 1975
TL;DR: The authors showed that gene differences in the I region of the H-2 complex prevent the development of T-B cell interactions irrespective of the existence of gene identities elsewhere in the H2 complex (including the I-C subregion).
Abstract: The data of our most recent investigations have mapped the relevant gene or genes coding for CI molecules to the I region of the H-2 complex of the mouse. Thus, T and B lymphocytes from donor mice which differ at genes in either the K , S or D regions of H-2 (or combinations of the latter), but which are identical for genes in the I region, are capable of developing cooperative immune responses. Conversely, gene differences in the I region, more precisely in the Ir-1A and Ir-1B subregions, prevent the development of T-B cell interactions irrespective of the existence of gene identities elsewhere in the H-2 complex (including the I-C subregion).
TL;DR: In the course of searching for T7 mutants that are unable to overcome restriction, it was discovered that mutants defective in gene 2 are able to plate on E. coli C with essentially normal efficiency, and most gene 7 mutants are ableto plate on both C and K strains.
TL;DR: A methylated nucleoside that chromatographed slightly ahead of 2′-O-methyladenosine (Am) is identified and it is found that it is common to mRNAs of human and mouse cells as well as at least one virus.
Abstract: MODIFIED 5′-terminal structures of the type m7G(5′)ppp(5′)Nm have been identified in various viral1–4 and cellular5–8 mRNAs. The 5′-terminal modification of mRNA may be carried out by specific guanylyl- and methyltransferases9 and the structure seems to be required for efficient in vitro translation10. Studies5 of the 5′-terminal sequences of HeLa cell mRNAs revealed a methylated nucleoside that chromatographed slightly ahead of 2′-O-methyladenosine (Am). We have now identified this novel nucleoside and found that it is common to mRNAs of human and mouse cells as well as at least one virus.
TL;DR: In the past decade the scope of the understanding of mechanisms of immune responses at the cellular level has broadened considerably and the delineation of the carrier recognition function of T cells and the growing awareness that their regulatory role spans a continuing spectrum ranging from suppression at one end to enhancement at the other have been particularly enlightening.
Abstract: In the past decade the scope of our understanding of mechanisms of immune responses at the cellular level has broadened considerably. Certain areas of investigation have been particularly fruitful in justifying an attempt to integrate various phenomena into a cogent working theory of cellular and molecular events involved in recognitive and regulatory processes in the immune system. First, the critical importance of the macrophages and possibly other accessory cells in antigen presentation for development of immune responses has been clearly elucidated {Unanue 1972). Second, the discovery of the role of thymus-derived (T) lymphocytes in governing induction and regulation of the responses of other T cells and of bone marrow-derived (B) lymphocytes has not only opened many new avenues for experimentation but also has forced upon us a complex conceptual framework in which to consider our phenomenological data (Miller & Mitchell 1969, Claman & Chaperon 1969, Katz & Benacerraf 1972). In this regard the delineation of the carrier recognition function of T cells and the growing awareness that their regulatory role spans a continuing spectrum ranging from suppression at one end to enhancement at the other have been particularly enlightening (Katz & Benacerraf 1972). Third, the discovery and identification of histocompatibility-hnked (H-linked) immune response (Ir) genes and their apparent role in the recognition functions of T lymphocytes provided the initial impetus to consider the existence of a comparably
TL;DR: Sensitized lymphocytes can transfer a state of delayed-type hypersensitivity to soluble protein antigens to naive mice only if donor and recipient share the I-A region of the H-2 gene complex, a requirement for an Ir-gene controlled mechanism which governs effective interaction between sensitized T lymphocytes and antigen presented on the surface of macrophages.
Abstract: Sensitized lymphocytes can transfer a state of delayed-type hypersensitivity to soluble protein antigens to naive mice only if donor and recipient share the I-A region of the H-2 gene complex. Identity at the K or D region is not essential. The restriction is unlikely to result from ineffective homing of the injected cells or from their early destruction. It is thought to reflect a requirement for an Ir-gene controlled mechanism which governs effective interaction between sensitized T lymphocytes and antigen presented on the surface of macrophages.
30 Sep 1975
TL;DR: The epidemiological implications of the discovery that antibiotic resistance genes can migrate from molecule to molecule are most significant, no longer should one simply think of the direct extension of drug resistance plasmids by transfer but rather of an enormous reservoir of genes available to insert into any DNA species.
Abstract: : The antibiotic resistance gene of R plasmids which encodes for ampicillin resistance resides upon a 3.7 x 3700000 dalton sequence of DNA, TnA, which can migrate (translocate) from plasmid to plasmid. The translocation of TnA occurs independently of normal bacterial rec functions so that it permits rearrangement and recombination of DNA species from diverse backgrounds. The insertion of TnA is mutagenic and may have either a polar effect or a promotor effect depending upon its orientation of insertion. Translocation sequences such as TnA are powerful tools for genetic research since insertion of a resistance gene into a DNA molecule provides a readily identifiable genetic and physical marker. This feature has been exploited to mark Ent and K plasmids and can be used for the construction of vaccine strains. The epidemiological implications of the discovery that antibiotic resistance genes can migrate from molecule to molecule are most significant. No longer should one simply think of the direct extension of drug resistance plasmids by transfer but rather of an enormous reservoir of genes available to insert into any DNA species.
TL;DR: IN androgen-resistant male mice of genotype Tfm/Y spermatogenesis is arrested at first meiotic division, likely to be due, at least in part, to the need for testosterone if sperMatogenesis is to proceed beyond prophase of first meiosis1.
Abstract: IN androgen-resistant male mice of genotype Tfm/Y spermatogenesis is arrested at first meiotic division. This is likely to be due, at least in part, to the need for testosterone if spermatogenesis is to proceed beyond prophase of first meiosis1. It would be somewhat surprising if the response to androgen involved any gene action in the developing sperm cell itself, since the locus of the gene for response to androgen, Tfm, is on the X chromosome2. The X–Y chromosome pair is believed to become genetically inactive during meiotic prophase3, and at stages beyond meiosis I only 50% of spermatocytes and spermatids possess an X chromosome.
TL;DR: The results firmly support the hypothesis that the number of α-globin structural genes in haemoglobin-H disease is duplicated and that α thalassaemia-1 and αThalassAemia-2 are caused by a defect of greater and lesser severity affecting alleles of a single α- globin locus.
Abstract: FOUR clinical syndromes are associated with α thalassaemia: (1) the silent carrier state (α thalassaemia-2) with no clinical effect; (2) heterozygous α thalassaemia (α thalassaemia-1) in which a more severe defect in α-chain synthesis produces microcytic red cells but little or no anaemia; (3) haemoglobin-H disease usually the combination of α thalassaemia-1 and α thalassaemia-2 resulting in mild to moderate haemolytic anaemia and (4) hydrops fetalis associated with haemoglobin Barts an invariably fatal condition which represents the homozygous state of α thalassaemia-1 (for recent reviews see refs 1 and 2). To explain these syndromes one hypothesis proposes that α thalassaemia-1 and α thalassaemia-2 are caused by a defect of greater and lesser severity affecting alleles of a single α-globin locus3. A second hypothesis is based on evidence that the α-globin structural gene is duplicated4; the four syndromes may be the result of involvement of one, two, three or all four α structural genes by thalassaemia. In this study we tested these hypotheses by measuring the number of α-globin structural genes in haemoglobin-H disease and the results firmly support the latter hypothesis.
TL;DR: Findings indicate that muscle and non-muscle tropomyosins are grouped into two similar but non-identical classes of protein, and is likely that both gene classes evolved from an ancestral gene by a process involving gene duplication.
TL;DR: Results lead to the conclusion that FeLV-related genes were transmitted from a rodent to cat ancestor and have been perpetuated in the germ line of cats.
Abstract: Reiterated gene sequences related to the RNA of feline leukemia virus (FeLV) are detected in all tissues of domestic cats and their close Felis relatives but not in more distantly related Felis species. Partially homologous viral gene sequences are found in rodent, and particularly rat, DNA. Together with the immunologic relationships observed between FeLV and endogenous rodent type C viruses, the results lead to the conclusion that FeLV-related genes were transmitted from a rodent to cat ancestor and have been perpetuated in the germ line of cats.
TL;DR: The induction of host DNA synthesis is impaired when cultures are infected with mutants of the A group at 42.5 C rather than 40 C, suggesting that the A function may be responsible for host induction.
Abstract: Host DNA synthesis is induced when CV-1 (monkey kidney) cell cultures are infected at 40 C with wild-type virions or with temperature-sensitive Simian virus 40 mutants of the "early" complementation group A. Host DNA synthesis is not induced when cultures are infected with mutants of the late complementation group D. The simplest explanation for these observations, that induction depends not upon the expression of some early gene function but rather on the presence of an active D protein in the infecting virion, has been examined. Indirect experiments suggest that this explanation is not correct. Moreover, the induction of host DNA synthesis is impaired when cultures are infected with mutants of the A group at 42.5 C rather than 40 C, suggesting that the A function may be responsible for host induction. The inability of D virions to induce host DNA synthesis may reflect their inability to "uncoat" at 40C.
TL;DR: In the (C57BL/6J X SJL)F1 hybrid, complementation between two parental nonresponder strains, each of which carried beta genes derived from different H-2 haplotypes, yet lacked functional alpha genes are noted.
Abstract: The immune response to the random linear terpolymer of L-glutamic acid, L-lysine, and L-phenylalanine (GLphi) is under dominant H-2-linked Ir gene control in the mouse. Matings between two nonresponder strains produced responder F1 hybrids, demonstrating complementation of the nonresponder alleles. This observation, coupled with the fact that several intra H-2 recombinant strains derived by recombination between two nonresponder parental haplotypes are also GLphi responders, indicated at least two dominant loci are concerned with responsiveness to this terpolymer. The complementary genes were termed alpha (tentatively localized in a new subregion of the H-2 complex, I-F) and beta, which maps in the I-A subregion. Generally, both the alpha(+) and beta(+) alleles are required for responsiveness. However, in the (C57BL/6J X SJL)F1 hybrid we noted complementation between two parental nonresponder strains, each of which carried beta genes derived from different H-2 haplotypes, yet lacked functional alpha genes. The possible cell levels at which these genes may function in the regulation of the immune response are discussed.
TL;DR: Cytoplasmic RNA, isolated from cells late after infection by adenovirus type 2 and fractionated by hybridization to specific fragments of adenOVirus DNA produced by cleavage with the endonuclease R-EcoRI, was used as template for protein synthesis in cell-free mammalian extracts.
Abstract: Cytoplasmic RNA, isolated from cells late after infection by adenovirus type 2 and fractionated by hybridization to specific fragments of adenovirus DNA produced by cleavage with the endonuclease R-EcoRI, was used as template for protein synthesis in cell-free mammalian extracts. Each of the R-EcoRI fragments of DNA selects RNA that encodes specific subsets of the viral polypeptides. From the known order of the R-EcoRI fragments, the following partial map is deduced: (III, IIIa, IVa2, V, P-VII, IX), (II, P-VI), 100K, IV-where the relative order of the components enclosed in parentheses has not yet been determined.