Showing papers on "Gene published in 1974"
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
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
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
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
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
TL;DR: Five Pillars of Evolution were culled from the accumulated evidence on molecular evolution and theoretical considerations of the population dynamics of mutant substitutions.
Abstract: The following five principles were deduced from the accumulated evidence on molecular evolution and theoretical considerations of the population dynamics of mutant substitutions: (i) for each protein, the rate of evolution in terms of amino acid substitutions is approximately constant/site per year for various lines, as long as the function and tertiary structure of the molecule remain essentially unaltered (ii) Functionally less important molecules or parts of a molecule evolve (in terms of mutant substitutions) faster than more important ones (iii) Those mutant substitutions that disrupt less the existing structure and function of a molecule (conservative substitutions) occur more frequently in evolution than more disruptive ones (iv) Gene duplication must always precede the emergence of a gene having a new function (v) Selective elimination of definitely deleterious mutants and random fixation of selectively neutral or very slightly deleterious mutants occur far more frequently in evolution than positive Darwinian selection of definitely advantageous mutants
467 citations
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
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
TL;DR: The rapid rate of gene rearrangement in mammals parallels both their rapid anatomical evolution and their rapid evolutionary loss of the potential for interspecific hybridization, and may be more important than point mutations as sources for evolutionary changes in anatomy and way of life.
Abstract: We have compared the relative rates of protein evolution and chromosomal evolution in frogs and mammals. The average rate of change in chromosome number has been about 20 times faster in mammals than in frogs. Whereas it takes only 3.5 million years, on the average, for a pair of mammal species to develop a difference in chromosome number, the corresponding period for frogs is 70 million years. In contrast, the rate of protein evolution in mammals has been roughly equal to that in frogs. The rapid rate of gene rearrangement in mammals parallels both their rapid anatomical evolution and their rapid evolutionary loss of the potential for interspecific hybridization. Thus, gene rearrangements may be more important than point mutations as sources for evolutionary changes in anatomy and way of life.
294 citations
TL;DR: It is thought that the most likely explanation for the marked molecular restriction on hybridization among mammals is that the ratio of regulatory evolution to protein evolution is higher for mammals than for frogs.
Abstract: To assess the significance of macromolecular sequence differences among species, we compared the serum albumins of 81 pairs of vertebrate species capable of producing viable hybrids. Micro-complement fixation experiments showed that the average difference between the albumins within such pairs was only 3 immunological distance units for placental mammals (31 pairs), but 36 units for frogs (50 pairs). Albumin immunological distance is strongly correlated with other measures of genetic distance, including those made with DNA annealing techniques. It therefore seems likely that mammalian species pairs capable of hybridization are far more similar at the macromolecular sequence level than is the case for most hybridizable frogs.
We think the most likely explanation for the marked molecular restriction on hybridization among mammals is that the ratio of regulatory evolution to protein evolution is higher for mammals than for frogs. Mammals may have experienced unusually rapid regulatory evolution; indeed, this could be the factor responsible for their unusually rapid anatomical evolution.
289 citations
TL;DR: In this paper, a family with C2 deficiency revealed evidence for close linkage between the C2 defect and the histocompatibility HL-A loci, and the possible significance of such linkage was discussed.
Abstract: HL-A analysis of a family with C2 deficiency revealed evidence for close linkage between the C2 defect and the histocompatibility HL-A loci. The propositus was homozygous both for C2 deficiency and the HL-A haplotype 10,W18. Among seven children of three double backcross matings, no recombinants were found. The possible significance of such linkage is discussed.
TL;DR: The requirements for killer cell production in the course of a mixed leukocyte reaction and the specificity of target cell lysis in the mouse were investigated using inbred strains carrying intra‐H‐2 recombinant chromosomes.
Abstract: The requirements for killer cell production in the course of a mixed leukocyte reaction and the specificity of target cell (PHA-blasts) lysis in the mouse were investigated using inbred strains carrying intra-H-2 recombinant chromosomes. Strong lytic activity was generated in all, and only those, responder-stimulator combinations which differed at either the H-2D or the H-2K, or both regions, even if the MLR incompatibility between responder and stimulator was very weak. Killing activity was specific and directed against determinants controlled by genes in the H-2K and H-2D regions. The slope of the killer dose-response curves is the same for either type of specificity. Quantitative comparison of the lytic activity of a given killer cell population on different targets demonstrated a dose effect of the number of specificities recognized. No significant killing against the Ir or the Ss-Slp regions of the H-2 complex could be detected.
AntiH2 sera, if directed against the killer cells, do not inhibit their activity, while they can block killing, if directed against the target. This inhibition is specific in that a serum that blocks killing against the H-2K specificity of a given target does not inhibit the lytic activity directed against the H-2D determinants on the same target.
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.
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.
TL;DR: Two independent groups show that the absence of all or part of the globin α-chain gene is the origin of the homozygous α thalassaemia.
Abstract: Two independent groups show that the absence of all or part of the globin α-chain gene is the origin of the homozygous α thalassaemia.
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.
TL;DR: This work concludes that a Chi mutation in phage λ stimulates Rec-mediated crossing over more to one side of itself than to the other, and whether recombination is measured “genetically” in standard crosses or "physically" in density-labeled crosses conducted in the absence of DNA replication is questionable.
Abstract: Crosses have been performed which identify phage mutants (chi) which cause recombinational hot spot activity in λ. The hot spot activity is found in crosses of red- gam- chi- strains in rec+ hosts; in the crosses reported here, both the chi- mutations and the hot spot are located near the right end of the chromosome. The hot spot occurs in standard crosses as well as under conditions which block DNA synthesis, and is dependent on a functional host recB gene.—The chi mutation is shown to be dominant, but the tests do not show whether chi is a gene or a site.
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 .
TL;DR: New stocks of mice carrying the autosomal recessive gene, retinal degeneration, have been developed and are characterized and a comparison is given of the advantages and disadvantages of several breeding schemes for propagating the rd and related genes.
Abstract: New stocks of mice carrying the autosomal recessive gene, retinal degeneration ( rd ), have been developed and are characterized in this report. The aim was to generate mutant and control mice that are (1) littermates, (2) distinguishable by linked marker gene(s) prior to recognizable phenotypic expression of the mutation, and (3) nearly identical at all genetic loci outside the chromosomal segment bearing rd and the marker mutations. C57BL/6J congenic strains carrying the linked genes rd , light ear ( le ), and viable dominant spotting ( W ) meet these criteria. The recombination percentages between these loci and their probable order is Wv -12- rd -1- le . The rd and le phenotypes on the C57BL/6J background appear not to interact with respect to expression of the photoreceptor cell degeneration. A comparison is given of the advantages and disadvantages of several breeding schemes for propagating the rd and related genes.
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.
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.
TL;DR: It is suggested that the predominant means for abolishing iso-1-cytochrome c by mutations are either through a complete loss, such as produced by chain terminating codons, or impairments through drastic changes of tertiary structure which lead to instability and thermolability.
Abstract: A medium containing chlorolactate has been devised to enrich for mutants that are unable to utilize lactate for growth, and therefore that may be defective in cytochrome c. Complementation tests of 6,520 chlorolactate-resistant mutants that were obtained spontaneously or induced with UV, ICR-170, or nitrosoimidazolidone resulted in the identification of 195 mutations at the cyc1 locus, which controls the primary structure of iso-1-cytochrome c. These 195 mutants, with 16 cyc1 mutants previously isolated, were examined for total cytochrome c by spectroscopic methods, growth on lactate medium, suppressibility by defined nonsense suppressors, mutational sites by x-ray-induced recombination, ability to revert, and in 86 cases, whether intragenic revertants contain altered iso-1-cytochrome c. Except for the deletion mutant cyc1-1, all of the mutants appeared to contain single-site mutations that could be assigned to at least 35 different sites within the gene. The cyc1 mutants either completely lacked iso-1-cytochrome c or contained iso-1- cytochromes c that were completely or partially nonfunctional. In spite of the fact that the cyc1 mutants obtained by the chlorolactate procedure were selected on the basis of defective function, 68% appeared to completely lack iso-1-cytochrome c. The remaining cyc1 mutants contained below normal amounts of iso-1-cytochromes c. Studies at several incubation temperatures indicated that these nonfunctional iso-1-cytochromes c were thermolabile. It is suggested that the predominant means for abolishing iso-1-cytochrome c by mutations are either through a complete loss, such as produced by chain terminating codons, or impairments through drastic changes of tertiary structure which lead to instability and thermolability.
TL;DR: Two large, stable populations of Drosophila melanogaster were surveyed at 21 allozyme loci on the second and third chromosomes and for chromosomal gene arrangements on those two chromosomes to interpret evidence of similar selective environments (ecological and genetic) in the two populations.
Abstract: Two large, stable populations (Texas and Japan) of Drosophila melanogaster were surveyed at 21 allozyme loci on the second and third chromosomes and for chromosomal gene arrangements on those two chromosomes. Over 220 independent gametes were sampled from each population. The types and frequencies of the surveyed genetic variation are similar to those observed previously and suggest only slight differentiation among geographically distant populations. Linkage disequilibrium among linked allozymes loci is only slightly, if at all, detectable with these sample sizes. Linkage disequilibrium between linked inversions and allozymes loci is common especially when located in the same arm. These disequilibria appear to be in the same direction for most comparisons in the two population samples. This result is interpreted as evidence of similar selective environments (ecological and genetic) in the two populations. It is also noted that the direction of these linkage disequilibria appears to be oriented with respect to the gene frequencies at the component loci.
TL;DR: The temperate bacteriophages P22 of Salmonella typhimurium and λ of Escherichia coli form viable hybrids in which the immunity, early control and DNA replication genes of P22 are substituted for the analogous λ genes.
Abstract: The temperate bacteriophages P22 of Salmonella typhimurium and λ of Escherichia coli form viable hybrids in which the immunity, early control and DNA replication genes of P22 are substituted for the analogous λ genes. The specificity of the early control and DNA replication genes differs between P22 and λ; the immunity of the hybrid is identical with that of the lambdoid coliphage 21. Implications for the evolution of viruses are discussed.
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.
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.
TL;DR: The hypothesis suggests specific experimental vectors designed to enhance information on the molecular basis of the morbid process which occurs with viral infection, and suggests that, although the dsRNA molecule may be viewed as a rather simple unit structure, the opportunity for further diversity in the biological activity of a given ds RNA molecule always exists.
Abstract: Double-stranded RNA, made as an intermediary substance in the replication of most, if not all, viruses, may play a much more important role in the pathogenesis and the recovery from virus infections than has hitherto been suspected. Apparently, dsRNA is used by both the challenge virus and the host cell in an attempt to gain "molecular control." Double-stranded RNA exerts a set of effects, which may be well balanced, not only at the level of the individual cell but also at the complex assemblage of these cells termed the organism (Fig. 1). In the cell, interferon synthesis is triggered, although interferon mRNA translation may not occur if dsRNA shuts off protein synthesis too quickly. In the whole organism, the disease severity will depend on how certain toxic reactions evoked by infection (such as cell necrosis and fever) are counterbalanced by an increase in the host defense mechanisms (for example, immune responsiveness and interferon production). Many aspects of the response, relating to either progress of, or recovery from, the disease, can be explained on the basis of a dsRNA. In addition to drawing attention to the biodynamic role of dsRNA, our hypothesis suggests specific experimental vectors designed to enhance our information on the molecular basis of the morbid process which occurs with viral infection. Finally, we suggest that, although the dsRNA molecule may be viewed as a rather simple unit structure, the opportunity for further diversity in the biological activity of a given dsRNA molecule always exists. Namely, each deviation from a perfectly double-helical arrangement introduces the possibility for emphasizing one biological reactivity at the expense of another. This latter structure-activity property may partially account for the extreme apparent diversity, commonly encountered, in the presentations of virologic illness. Appendix note added in proof. Subsequent to submission of this text, we have found that the potent mitogen effect of dsRNA for lymphocytes (murine and human) is also exquisitively sensitive to the fidelity in base pairing of the input polymer pair (59). For example, infrequent "loops" (one nucleotide per 20 base pairs) in an otherwise perfectly helical rI(n) (.) rC(n) molecule [for example, rI(n) (.) r(C(19,)U)(n)] strongly changes its mitogenic properties. This observation, which supports our thesis that a "fine structure" term can be developed for other reactions triggered by dsRNA's in biological systems, emphasizes that diverse biological effects may be encountered with an ostensibly uniform family of dsRNA's.
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.
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.
TL;DR: The findings indicate a pleiotropic effect of the retinoblastoma gene which may act as an initiator in two forms of neoplasia.
Abstract: Vigorous treatment of retinoblastoma in the last 30 years has resulted in a large population of survivors with useful vision, in which the late effects of genetically associated tumours can be seen. An increase in second primary tumours, mainly osteogenic sarcoma, has been found in those children who carry the germinal mutations, and not in the majority of survivors of unilateral disease. The findings indicate a pleiotropic effect of the retinoblastoma gene which may act as an initiator in two forms of neoplasia.