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G A Dover

Publications and source records attributed to G A Dover.

At least 55 records · Page 3Linked to original sources
PubMed1987

Evolutionary divergence of promoters and spacers in the rDNA family of four Drosophila species. Implications for molecular coevolution in multigene families.

The organization and sequence of the rDNA multigene family of four Drosophila species (melanogaster, orena, virilis and hydei) have been compared in order to understand the quality and quantity of the differences which are involved with interspecific divergence of promoters and the polymerase I complexes (molecular coevolution). Each species has an intergenic spacer (IGS) made up of subrepeats which contain duplications of the promoter. Major structural and point-mutational differences exist, most of which have been spread by unequal crossingover through the family and species. Structural differences involve the types, lengths and copy-number of the IGS subrepeats, and the lengths and position of "unique" regions between blocks of repeats. The 240 base-pair repeat array shared by D. melanogaster and D. orena has been replaced by a 220 base-pair repeat, and the 95 and 330 base-pair arrays are absent altogether in D. virilis and D. hydei. The length of the "unique" region between the 240/220 base-pair arrays and the start of transcription varies, with the unusual situation of the last of the 220 repeats ending at the external transcribed spacer (ETS) boundary in D. virilis. Other structural differences involve regions of high cryptic simplicity arising from slippage in D. virilis and D. hydei IGSs. Sequence analysis of IGS and the ETSs indicates that the rDNA is not uniformly divergent throughout its length. Apart from the genes, there are regions of relatively high conservation covering the promoter regions and at some but not all potential RNA processing sites. The conserved promoter regions are more extensive within each pair of species D. melanogaster versus D. orena and D. virilis versus D. hydei, in keeping with their phylogenetic distances. Slippage-like mechanisms are involved with large numbers of deletions/insertions that make up the ETS differences between the species. Patterns of shared mutations between IGS subrepeats indicate stages of transition during rDNA differentiation by continual homogenization. The simultaneous operation of different turnover mechanisms, at different periodicities and rates, generates a complex picture of reorganization, some of which would influence the process of molecular coevolution in the family.

Animals↗
PubMed1987

A novel arrangement of sequence elements surrounding the rDNA promoter and its spacer duplications in tsetse species.

Variation in organization and sequence of the rDNA of six species of tsetse fly (Glossina) has been investigated. Several novel tsetse-specific features have been uncovered. Like many other species the spacer is composed of subrepeats, which in some species contain duplications of the true promoter at the spacer-ETS boundary. In tsetse, however, the first 90 base-pairs of the external transcribed spacer (ETS) (that is, +1 to +90 after transcription initiation) is the 3' end of the last subrepeat. The absence of a "unique" region between the last subrepeat and the ETS suggests that the tsetse rDNA unit may consist of multiple true promoters, that is there is no single ETS boundary. Furthermore, interspecific comparisons show that the 90 base-pair region is part of a conserved 202 base-pair region, consisting of 72 base-pairs upstream from the initiation site and a further 40 base-pairs downstream, which is shared by all promoters other than the last. In genera other than tsetse, subrepeat lengths between species are generally similar; in tsetse they differ due to (1) variation in copy-number of the subsubrepeat motif A9T6CAG, and (2) the presence of large regions flanked by direct simple repeats such as GA5 or TGGTCTC. Slippage-like mechanisms are probably responsible for (1), and recombination and subsequent excision involving the direct repeats for (2). Different structural and sequence variants are seen to be homogenized in the family and fixed in each species, reflecting continual unequal crossing-over. However, notwithstanding this process of differentiation, the available comparisons also reveal that there are two small conserved regions between Glossina and Drosophila: one is part of the promoter and the other is an ETS processing site. Such intergeneric and interspecific differences are discussed in relation to the problem of the maintenance of several essential functions within the rDNA repeating unit despite the continual differentiation of the unit into novel arrangements.

Animals↗
PubMed1987

Tsetse fly rDNA: an analysis of structure and sequence.

A genomic library of Glossina morsitans morsitans (tsetse fly) has been constructed in the phage vector EMBL 4 and a complete rDNA unit isolated by using a D. melanogaster rDNA clone as a probe. The overall organisation is typical of higher eukaryotes, including an intergenic spacer consisting of a subrepeating structure. Atypically, however, the 45S precursor RNA promoter was shown to lie within the last subrepeat by S1 mapping; i.e. the last subrepeat extends 90 bp into the ETS. The sequence of the spacer subrepeats, the ETS and the first 151 nucleotides of the 18S gene was determined. Comparisons with the corresponding regions of other higher eukaryotes, including insects shows that the ETS has completely diverged, raising questions concerning their functional significance and evolutionary retention; depending on the method of alignment, only two short regions of reasonable homology are shared with Drosophila species: a stretch of nucleotides around the transcription initiation site, and AACATA at the NTS-18S gene junction; and the functionally important G at -16, conserved in all other examined species, is displaced no matter what method of alignment is used. These and other features reflect continual processes of change in the rDNA family to which the several functions of the repeating unit need to adjust.

Animals↗
PubMed1987

DNA turnover and the molecular clock.

Many detailed studies on the mechanisms by which different components of eukaryotic nuclear genomes have diverged reveal that the majority of sequences are seemingly not passively accumulating base substitutions in a clocklike manner solely determined by laws of diffusion at the population level. It appears that variation in the rates, units, biases, and gradients of several DNA turnover mechanisms are contributing to the course of DNA divergence. Turnover mechanisms have the potential to retard, maintain, or accelerate the rate of DNA differentiation between populations. Furthermore, examples are known of coding and noncoding DNA subject to the simultaneous operation of several turnover mechanisms leading to complex patterns of fine-scale restructuring and divergence, generally uninterpretable using selection and/or neutral drift arguments in isolation. Constancy in the rate of divergence, where observed over defined periods of time, could be a reflection of constancy in the rates and units of turnover. However, a consideration of the generally large disparity between rates of turnover and mutation reveals that DNA clocks, which would be independently driven by turnover in separate genomic components, would tend to be episodic. The utility of any given DNA sequence for measuring time and species relationships, like individual proteins, is proportional to the extent to which all contributing forces to the evolution of the sequence, internal and external, are understood.

Biological Evolution↗
PubMed1986

Conservation and divergence in multigene families: alternatives to selection and drift.

It is generally assumed that conservation and divergence of DNA signify function (selection) and no function (drift), respectively. This assumption is based on the view that a mutation is a unique event on a single chromosome, the fate of which depends on selection or drift. Knowledge of the rates, units and biases of widespread mechanisms of non-reciprocal DNA exchange, in particular within multigene families, provides alternative explanations for conservation and divergence, notwithstanding biological function. Such mechanisms of DNA turnover cause continual fluctuations in the copy-number of variant genes in an individual and, hence, promote the gradual and cohesive spread of a variant gene throughout a family (homogenization) and throughout a population (fixation). The dual processes (molecular drive) of homogenization and fixation are inextricably linked. Data are presented of the expected stages of transition in the spread of variant repeats by molecular drive in some non-genic families of DNA, seemingly not under the influence of selection. When a molecularly driven change in a given gene family is accompanied by the coevolution (mediated by selection) of other DNA, RNA or protein molecules that interact with the gene family then biological function is observed to be maintained despite sequence divergence. Conversely, the mechanics of DNA turnover and a turnover bias in favour of ancestral sequences can dramatically retard the rate of sequence change, in the absence of function. Examples of the maintenance of function by molecular coevolution and conservation of sequences in the absence of function, are drawn mainly from the rDNA multigene family.

Animals↗
PubMed1986

Transcription of the tandem array of ribosomal DNA in Drosophila melanogaster does not terminate at any fixed point.

Transcription termination of the polymerase I transcribed rRNA genes is thought to occur at or closely behind the end of the 28S gene coding region. We show here that this is not the case for Drosophila melanogaster. Nuclease S1 mapping of total RNA and a nuclear ;run-on' assay reveal that there is no defined point of termination throughout the whole spacer separating the two genes. Since the rRNA genes in D. melanogaster are organized in tandem arrays, this implies that readthrough transcription of one unit can occur up to, and possibly through, the promoter of the next unit. Readthrough transcription might be a component of transcription enhancement in a tandem array of genes.

Journal Article↗
PubMed1985

Conservation of major nuclease S1-sensitive sites in the non-conserved spacer region of ribosomal DNA in Drosophila species.

We have analysed nuclease S1-sensitive sites in cloned ribosomal DNA repeats from Drosophila melanogaster, D. hydei and D. virilis. All species contain major S1-sensitive sites in the spacer near the region of transcription termination, albeit with somewhat different positions and sensitivities. The same sites are also sensitive to the single-strand specificity of Bal31 nuclease at neutral pH. Additional major sites exist at each end of the intervening sequence within the 28 S gene of non-transcribed intervening-sequence-positive ribosomal DNA units of D. hydei. Only minor sites, however, were detected in the Pol I promoter regions. This is in contrast to Pol II transcribed genes, where S1 hypersensitivity becomes apparent at the 5' ends during gene expression. We have sequenced and mapped the S1 sites in the D. hydei spacer. They consist mainly of alternating A and T nucleotides that could form small cruciform structures. Cross-hybridization at low stringencies between the relevant S1-sensitive spacer regions of the three species indicates that the sites lie within very divergent sequences. We discuss the potential functional significance of S1 sites in rDNA spacers and intervening sequences, and the manner in which they might be maintained during rDNA sequence divergence.

Animals↗
PubMed1985

Transition stages of molecular drive in multiple-copy DNA families in Drosophila.

Multigene and non-genic DNA families are in a state of turnover and hence are continually being replaced throughout a population by new variant repeats. To quantify such molecular processes, in the absence of selection, it is necessary to find and compare stages of transistion during the homogenization of at least two non-genic families evolving in parallel in a closely related group of species. Detailed sequence analysis of patterns of variation, at each nucleotide position considered independently, amongst repeats of two tandem DNA families from seven related Drosophila species, reveals all stages of transition during the spread of randomly produced variant repeats. Variant repeats are found at different stages of homogenization and fixation in a population, irrespective of the loci, chromosomes or individuals from which they were cloned. Differences between the families in the relatively small number of variants at each transition stage and the greater number of fully homogenized and fixed variants between species of greater divergence indicate that the process of spread (molecular drive) is rapid relative to the mutation rate and occurs at seemingly different constant rates for each family. Occasional gene conversions, in addition to unequal exchanges, have contributed to family turnover. The significance of these results to the evolution of functional multigene families and divergence and conservation of sequences is discussed.

Journal Article↗
PubMed1984

Unexpectedly slow homogenisation within a repetitive DNA family shared between two subspecies of tsetse fly.

Repetitive DNA families in sexual species are subject to a variety of turnover mechanisms capable of homogenising newly arising mutations. Very high levels of homogeneity in DNA families in some species of Drosophila indicate that the rate of turnover is fast relative to that of mutation. To gauge the generality of such phenomena, we cloned and sequenced individual members of homologous repetitive DNA families from two subspecies of tsetse fly, Glossina morsitans centralis and G. morsitans morsitans. Unexpectedly high levels of variation were found within each subspecies, averaging 24% and 31%, respectively. Contiguous repeats and repeats cloned at random were comparably divergent. Nevertheless, it was possible to identify three instances of apparent homogenisation, each being, remarkably, of an insertion/deletion nature. We conclude that the rate of turnover in the tsetse families is comparable to that of most mutations, and discuss the possible parameters affecting flux in these families.

Animals↗
PubMed1984

The cohesive population genetics of molecular drive.

The long-term population genetics of multigene families is influenced by several biased and unbiased mechanisms of nonreciprocal exchanges (gene conversion, unequal exchanges, transposition) between member genes, often distributed on several chromosomes. These mechanisms cause fluctuations in the copy number of variant genes in an individual and lead to a gradual replacement of an original family of n genes (A) in N number of individuals by a variant gene (a). The process for spreading a variant gene through a family and through a population is called molecular drive. Consideration of the known slow rates of nonreciprocal exchanges predicts that the population variance in the copy number of gene a per individual is small at any given generation during molecular drive. Genotypes at a given generation are expected only to range over a small section of all possible genotypes from one extreme (n number of A) to the other (n number of a). A theory is developed for estimating the size of the population variance by using the concept of identity coefficients. In particular, the variance in the course of spreading of a single mutant gene of a multigene family was investigated in detail, and the theory of identity coefficients at the state of steady decay of genetic variability proved to be useful. Monte Carlo simulations and numerical analysis based on realistic rates of exchange in families of known size reveal the correctness of the theoretical prediction and also assess the effect of bias in turnover. The population dynamics of molecular drive in gradually increasing the mean copy number of a variant gene without the generation of a large variance (population cohesion) is of significance regarding potential interactions between natural selection and molecular drive.

Biological Evolution↗
PubMed1984

Genetic relationships between subspecies of the tsetse fly Glossina morsitans inferred from variation in mitochondrial DNA sequences.

A 750 base pair segment of DNA from the tsetse fly Glossina morsitans morsitans was isolated by means of molecular cloning. It was shown by DNA hybridization to have substantial sequence homology with a defined region of the mitochondrial genomes of several Drosophila species. When used as a probe against DNA prepared from single tsetse flies, the cloned sequence revealed local restriction site variation between members of the G. morsitans subspecies complex. This feature was used to demonstrate maternal inheritance of the sequence in progeny of hybrid crosses and to assemble comparative restriction maps for a 3-kilobase segment of each mitochondrial genome. The data obtained from these exercises point to a higher genetic identity between G. m. morsitans and G. m. centralis than between either form and G. m. submorsitans.

Animals↗
PubMed1983

Unequal exchanges and the coevolution of X and Y rDNA arrays in Drosophila melanogaster.

We have examined the molecular basis of the response of individuals of D. melanogaster to artificial selection for high and low abdominal bristles. By monitoring the fate of particular rDNA spacer length variants associated with individually isolated X and Y chromosomes, we show that flies from the low bristle number selection lines have undergone an unequal exchange between the X and Y rDNA arrays. Such exchanges result in translocations between X and Y chromosomes, visualised as X.Y compound chromosomes at mitosis. Transfer of few copies of a length variant between X and Y indicates a clustering of variants. Flies that have reverted back to wild-type seemingly have undergone a second unequal exchange, giving rise to a compound X.Y chromosome containing Y rDNA of normal amounts. Unequal exchanges between X and Y rDNA arrays could contribute to the observed coevolution of rDNA sequences on these chromosomes. The biological significance of this outcome is discussed.

Animals↗
PubMed1983

Population genetics of multigene families that are dispersed into two or more chromosomes.

The evolution of multigene families whose members are dispersed into two or more nonhomologous chromosomes is studied from the standpoint of population genetics. By using a simple model of gene conversion, equilibrium and transient properties of the probability of identity of genes belonging to the family are investigated. Also, the time until fixation of a mutant belonging to a subdivided multigene family is studied by an approximation method. It is shown that dispersion of the family into two or more chromosomes has a relatively minor effect on the extent of identity between genes, unless the conversion rate between genes on nonhomologous chromosomes is extremely low, or unless the number of nonhomologous chromosomes on which gene members are dispersed is large.

Animals↗
PubMed1982

Molecular drive.

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Animals↗
PubMed1982

Multiple Pol I initiation sequences in rDNA spacers of Drosophila melanogaster.

Sequence analysis of the rDNA nontranscribed spacer (NTS) of D.melanogaster shows that it contains many regions that are perfectly homologous with the Pol I transcription initiation site. Each initiation site homology is contained within a 240 base pair repeated sequence which are organised in a tandem array terminating 140 bases pairs upstream from the transcription initiation site. We discuss the significance of these regions and the maintenance of multiple homologies against the observed high rate of spacer divergence between related Drosophila species. In addition there are two other regions of repetition in the NTS: a 90 base pair periodicity commencing 16 bases downstream from the 3' end of the 28S gene and a number of 340 base pair repeats. A similar complex of different periodicities has been described in Xenopus and may be a general feature of NTS sequences.

Animals↗
PubMed1980

The specific organisation of satellite DNA sequences on the X-chromosome of Mus musculus: partial independence of chromosome evolution.

DNA was isolated from a chinese hamster/mouse hybrid cell line containing a single mouse chromosome, the X-chromosome, and digested with a variety of restriction endonucleases known to cut mouse satellite DNA. After agarose gel electrophoresis and transfer to nitrocellulose, hybridisation was carried out to a radioactive mouse satellite DNA probe. In this manner the organisation of satellite sequences at an individual chromosome was determined. We have found that the organisation of centromeric satellite DNA sequences on the mouse X-chromosome differs from that of other chromosomes in the complement. The nature of the differences suggests features of evolution of highly repeated sequences within a karyotype.

Animals↗