Showing papers in "Genetics Research in 1964"

A mechanism for gene conversion in fungi.

Abstract: A mechanism for gene conversion is proposed which overcomes many of the difficulties that any copy choice model encounters. It is suggested that along with general genetic pairing of homologous genomes at meiosis, effective pairing over short regions of the genetic material occurs at the molecular level by the separation of the strands of the DNA double helices, followed by the annealing of strands from two homologous chromatids. If the annealed region happens to span a heterozygous site, mispairing of bases will occur. Such a situation may be analogous to that in DNA which is damaged by mutagens; the same or similar repair mechanisms may operate, and these, by adjusting the base sequences in order to restore normal base pairing, would bring about gene conversion in the absence of any genetic replication. The model indicates how precise breakage and rejoining of chromatids could occur in the vicinity of the conversion, so that conversion would frequently be accompanied by the recombination of outside markers. The model also proposes that the distance between two mutant sites on a fine structure map depends not so much on the frequency of a recombinational event occurring between them, but rather on the degree of inhibition of the processes of genetic pairing by the mutants themselves. The model will explain almost all the data in a formal way, and it has the advantage over copy choice mechanisms for gene conversion in (1) being compatible with semi-conservative replication of DNA, (2) not invoking DNA synthesis during or after genetic pairing, (3) providing a molecular mechanism for close specific pairing, (4) making it unnecessary to postulate sister strand exchange or a process akin to this, (5) suggesting why rates of gene conversion in opposite directions are sometimes unequal and (6) providing an explanation of the clustering of mutant sites, a basis for map expansion and for the apparently capricious departure of fine structure maps from additivity. Although the model proposed is a general rather than a specific one, it suggests that the process of conversion and intragenic recombination is more complex than is usually believed, since it depends on several interacting factors. Nevertheless, it is hoped that the introduction of a model with this complexity will help to stimulate specific experiments, and that these will provide definitive information which would never be obtained if simpler models of conversion and intragenic recombination were believed to explain the genetic data sufficiently well.

The overall rates of dominant and recessive lethal and visible mutation induced by spermatogonial X-irradiation of mice

Abstract: 1. Hybrid (C3H♀ × 101♂) male mice were given two doses of 600 r. acute x-irradiation eight weeks apart and outcrossed at the end of their sterile period. Their fully fertile sons were outcrossed and daughters of these sons were backcrossed to them, in order to study the rates of induction in spermatogonia of dominant and recessive lethal and visible mutations, as well as dominant semi-sterility.2. F1 litter-size decreased by 15·2% at birth and 15·8% at weaning age, as compared with controls. This decrease was very largely due to dominant lethality acting at about the time of embryonic implantation. There was also a highly significant increase in the incidence of heritable semi-sterility, the estimated rate of induction of reciprocal translocations being 3·3% per gamete.3. The dominant lethality was shown to be partly a secondary consequence of induced translocation heterozygosis. The estimated overall rate of dominant lethal induction was 10·6% per gamete, with ‘primary’ dominant lethals induced at a rate of 4·0% per gamete.4. The estimated mutation rate to dominant visible mutations was 4·6 × 10-7/gamete/r., but this was based on only two mutations in the irradiated series.5. In the backcross generation there was again significantly more embryonic death in the irradiated series, mainly at the small mole stage and this was attributed to induced lethal mutation. The survival in the irradiated series was 96·80% of that in the controls and from this the rate of induction of recessive lethals was calculated to be 2·5 × 10-4/gamete/r. There was no evidence of the induction of lethals acting later than 14 days' gestation.6. The estimated rate of induction of recessive visible mutations was 1·8 × 10-5/gamete/r., but the results showed heterogeneity, probably due to personal factors.7. No significant sex-ratio differences were found.8. The results were compared with those of specific locus and other relevant experiments. The rates of induction of recessive lethal mutations and of recessive visibles were both lower than might have been expected. On these results the mouse was only 4–5 times more sensitive than Drosophila to the mutagenic effects of radiation.

The genetics and morphology of two ‘luxoid’ mutants in the house mouse

Abstract: 1. Dominant hemimelia (Dh) and postaxial hemimelia (px) both belong to the luxoid group of mouse mutants, tending to cause luxation of limb-bones associated with hemimelia and polydactyly or oligodactyly.2. Dh is about 4·8 units from leaden in linkage group XIII, while px is about 2·9 units from the microphthalmia locus in linkage group XI.3. The nature and range of skeletal anomalies found in Dh heterozygotes closely mimic those found in luxate heterozygotes and homozygotes. As in luxate, only the preaxial side of the hind-limb is affected, with (i) polydactyly or oligodactyly (sometimes also syndactyly), (ii) tibial hemimelia, (iii) reduction and fragmentation of the femur, (iv) reduction of the pubis. The more proximal the anomaly the less frequently does it occur; about 4% of Dh/ + mice show no limb anomaly. The defects in Dh homozygotes are similar but usually more extreme, with severe oligodactyly, loss of tibia, fragmentation of femur and reduction of pubis.4. All mice carrying Dh lack the spleen. Stomach size is reduced slightly in Dh/ + and greatly in Dh/Dh mice. In Dh/ + mice, the left kidney is either flattened antero-ventrally or (less frequently) hydropic; the right seems normal. Dh/Dh mice nearly always have severe hydronephrosis, as well as posterior visceral defects similar to those of the ‘uro-recto-caudal syndrome’. They usually die before weaning, but a few survive to maturity and a female has even bred.5. Preliminary developmental studies show that Dh/Dh skeletal defects can be traced back to the precartilaginous stage.6. When homozygous, px affects the postaxial side of the fore-limb and sometimes of the hind-limb also; a large ‘foramen infraspinatum’ is always present in the scapula. There may also be (i) oligodactyly and occasional syndactyly, (ii) ulnar hemimelia, (iii) distal reduction and distortion of the femur. Fore-limbs tend to be more severely affected on the right, but hind-limbs on the left. Extra sesamoid bones occur on the extensor side of digits in all four feet and are associated with extra tendons.7. Both sexes are sterile and show anomalies of the paramesonephric (Mullerian) ducts. In the female, the vagina is wholly or partly double and the uterine tubes uncoiled, with an abnormal relationship to the ovary. In the male the paramesonephric duct persists in the adult, while the vas deferens runs into the distal end of the vesicular gland instead of into the urethra. The epidermis of manus and pes shows abnormal dark papillae on the extensor side.8. The mean number of presacral vertebrae is reduced by 0·8 in Dh/ + and 1·6 in Dh/Dh mice. It is also reduced in high-grade postaxial hemimelics.9. The relationships of these two genes to other luxoid mutants are discussed.

Elements of the S -gene complex

Abstract: Cultivated plants of Nicotiana alata are self-incompatible and are of two kinds: normal (N); and exceptional (M). N plants are reciprocally compatible with N. langsdorffii; M plants are compatible only as males. M plants contain an unusual allele, SFI, which has a dual action in the style: it rejects both self-pollen, and Sf pollen from N. langsdorffii. The overall results agree with the assumption that the SFI gene produces two kinds of specificity in the style: primary specificity, which is responsible for the rejection of Sf pollen; and secondary specificity, which is responsible for the rejection of self-pollen as in SI alleles generally. The genetic sub-units concerned must be closely linked; there was no evidence for their dissociation in the 599 plants studied.In both compatible and incompatible pollinations, SFI pollen grows more slowly than SI and, in addition, appears to depress the normal rate of growth of SI pollen. In consequence, crosses SfSf × SISFI ♂ yielded significantly fewer S.I. plants than the 50% expected. The two kinds of pollen grew at comparable rates, however, when F1 (M × M) plants involving parents from different original sources were backcrossed to SfSf ♀. Progenies then showed the expected 1:1 ratio of S.I. to S.C. plants. These results are assumed to be due to differential behaviour of the SFI allele according to its genetic background. The change in background would be from a degree of homozygosity, in plants from the same source, to a degree of heterozygosity, in crosses between plants from different sources.The high incidence of the SFI gene in N. alata is considered to be due to the advantage it confers on a self-incompatible population when it is overlapping with a related self-compatible population (having the Sf gene). Plants carrying an SFI allele, by rejecting the Sf pollen, will restrict the spread of inbreeding and so be favoured by selection.The origin of the SFI and Sf alleles are discussed in relation to the author's hypothesis of S-gene structure.

Regular responses to selection 2. Recombination and accelerated response

Abstract: 1. It has been shown that the lines dp 1, dp 2, vg 4 and vg 6 of Thoday & Boam (1961) each have two high sternopleural chaeta number genes or ‘effective factors’ between h and eyg in chromosome III. Their line dp 6 does not contain these two genes. 2. Lines derived from ancestors of dp 2 and vg 4 before the latter produced their accelerated responses have third chromosomes affecting chaeta number as if they had only one or other of these genes. 3. Of the three stocks from which all the lines derived, one, Inbred Oregon, lacks these genes. The second, vg/vg , has third chromosomes similar in effect to Oregon. The third, dp/dp , was heterogeneous, having a class of third chromosomes similar in effect to those of Oregon and a class similar to those having one high gene. 4. It is suggested that the history of the accelerated response in dp 1, dp 2 and vg 4 was as follows. Initially most of these third chromosomes were − − at the two loci, but a minority (derived from the dp/dp stock) were + − and − + (where + indicates the allele increasing chaeta number. Selection would reduce the frequency of − −, and hence increase the proportion of + −/− + heterozygotes and the probability of recombination to produce + +. Origin and multiplication of + + would account for the accelerated response.

Dosage compensation and sex-chromatin in non-mammals

Abstract: 1. Inactivation of one X chromosome in somatic cells of female mammals is a form of dosage compensation of sex-linked genes, but the mechanism is entirely different from that operating in Drosophila . The latter is designated as dosage compensation sensu strictu . 2. There is no dosage compensation of barred, sex-linked dilution or slow-feathering in domestic fowls, of almond or faded in pigeons, or of cinnamon in canaries. Among Lepidoptera the same is true of sex-linked melanism in Lymantria monacha and of a locus controlling haemolymph colour in Choritoneura spp. There is no positive evidence that dosage compensation occurs outside Drosophila and mammals. 3. Sex-chromatin in female birds (heterogametic) has been reported by several authors; the genetical evidence is against the possibility that this represents (as in mammals) an inactivated X chromosome. Sex-chromatin in the heterogametic sex also occurs in some (not all) Lepidoptera and Heteroptera; in Heteroptera it usually represents a heteropyknotic Y chromosome. 4. Some complications in Muller's theory of dosage compensation sensu strictu are discussed. Not all ‘compensatory modifiers’ are necessarily sex-linked. 5. The problem of dosage compensation in species with impaternate males is discussed; fused in Habrobracon is not compensated.

The parasexual cycle in Verticillium albo-atrum

Abstract: Genetic recombination through the parasexual cycle, or some very similar system, was demonstrated. Diploid strains were very unstable, yielding about 95% haploid conidia from three-week-old cultures This high frequency of haploid segregants was at least partly attributable to greater sporulation of haploid mycelium, but may also reflect a higher frequency of haploidization than that found in Aspergillus nidulans.Mitotic crossing-over also occurred frequently, and gave segregants homozygous for some markers but heterozygous for others. It was also detectable by changes in the phase of linked markers occurring during vegetative growth. Some heterozygous segregants were either aneuploids, or were formed by double mitotic crossovers.Haploid segregants, derived from nuclei which had previously undergone mitotic crossing-over, were often recovered. This coincidence of mitotic crossing-over and haploidization in one nuclear lineage, together with the probable occurrence of double mitotic crossovers, makes mitotic analysis less clear cut than in Aspergillus nidulans.

Diabetes insipidus associated with oligosyndactyly in the mouse.

Abstract: 1. A mild diabetes insipidus is associated with the oligosyndactyly caused by the dominant gene Os. No recombinants were observed between the diabetes and the oligosyndactyly so the diabetes is probably a pleiotropic effect of the Os gene.2. There are one or more modifying genes which in combination with Os enhance the manifestation and cause a severe diabetes insipidus. This affects both sexes and becomes progressively worse in older animals, the average water intake reaching 50–60 ml. per 24 hours, or 1·7 times the body weight.3. The modifying gene or genes, in the absence of the Os gene, themselves produce a mild diabetes insipidus, which becomes severe in some old females.4. The severe diabetes insipidus associated with Os and the modifying genes together is probably renal in origin.

Genetic divergence in M. Vetukhiv's experimental populations of Drosophila pseudoobscura 1. Rudiments of sexual isolation*

Abstract: Weak but statistically significant sexual isolation has been demonstrated among Vetukhiv's six experimental populations of Drosophila pseudoobscura, all originally descended from founders taken from cultures of the same hybrids from four geographic localities. These six populations were maintained separately for almost 4½ years and then tested for the existence of sexual isolation. The sexual isolation has arisen in the absence of any selection for isolation, evidently as a by-product of genetic divergence.

The effects of x-rays on quantitative characters

Abstract: 1. The rate of production by X-rays of new genetic variation in two quantitative characters in Drosophila melanogaster (sternital and sternopleural bristles) has been investigated, using ‘plateaued’ populations which had reached the limit under artificial selection and, for sternital bristles only, populations which had been made genetically invariant by inbreeding. The genetic variation was always measured by the response of the population to selection. The X-rays dose given in any generation was always 1800 r. to adults.2. Seven plateaued lines had eight cycles of alternate irradiation and selection, each with its non-irradiated control. All the responses were small but in three lines they were significantly greater after irradiation.3. Selection was applied to three different inbred lines, genetically marked to detect contamination, after varying periods of irradiation. At the same time, the inbred lines and lines derived from them which had been mass mated in bottles were selected. The irradiated populations showed a greater response. The new genetic variance produced by the irradiation was approximately 10−5 units/r. The estimate of the dose required to introduce new variation equal to that in a standard outbred population was 500,000 r.4. The effective population size was an important factor in the interpretation of some of these results on the long-term effects of radiation. By observing the variation between replicate lines in the frequency of a gene with a visible effect under these culture conditions (i.e. in a single culture bottle) the effective population size was estimated at sixty. Outbred populations kept under these conditions for many generations showed a reduction of genetic variability in agreement with this value.5. To investigate the possibility that the deleterious genes produced by irradiation would interfere with the response to artificial selection, a standard outbred population was irradiated and selected. In spite of the observed high frequency of recessive lethals produced, the response to selection was very similar to that of the standard population.

Egg albumen polymorphisms in the fowl: The ovalbumin locus

Abstract: 1. Ovalbumin was shown, by starch gel electrophoresis, to exist in two genetically different forms, A and B. It was suggested that these are determined by two alleles at one locus, named Ov.2. Ovalbumin of each genetic type is electrophoretically heterogeneous. Dephos-phorylation of each type with human prostatic phosphatase and calf intestinal phosphatase removed some of the heterogeneity, but some remained.3. The genetic difference was shown not to reside in the fragment released from ovalbumin by the proteolytic enzyme subtilisin.4. The genetic difference was evident in the ovalbumin present in the fluid contained in right oviduct cysts.

The ecological genetics of growth in Drosophila 7. The role of canalization in the stability of growth relations

Abstract: 1. Similar changes in the body-size of Drosophila melanogaster have been achieved by different developmental pathways, especially either by altering the duration of the early exponential phase of larval growth or by influencing the growth rate in the phase which is independent of time. 2. Such changes have been effected by selecting in the same population for larger or smaller size or shorter development time on chemically defined media, deficient in alternative nutrients. Selection for larger size on media deficient in protein or choline does not involve correlated changes in the larval period, whereas selection on media deficient in RNA does. The evidence suggests that shortage of this nutrient may be uniquely favourable for promoting a correlated change between body-size and duration of the larval period. 3. Strains which differ in presence or absence of such correlation are characteristically different with respect to gene-environment interaction. In the former, the differences due to selection are generally more fully or completely expressed when the diet is changed whereas in the latter this is not so, and different, especially competitive condition, leads to a drastic reduction of the difference. 4. How far the expression of the differences due to selection are affected, when the diet is altered, is also influenced by how long selection has been carried out. In early generations, the difference is only or best expressed in the special conditions provided during selection, but later on the changes due to selection are either fully expressed or partly so, as noted above. 5. Many of the differences in gene-environment interaction between selected strains can be accounted for in terms of variation in the duration of the exponential phase. Thus two lines selected for small body-size on low RNA or low protein diets responded in different ways to the same nutritional change—one became relatively larger and took porportionately longer to develop, the other became relatively smaller and developed in a shorter time. 6. There is clear evidence from various tests in which the amino-acid composition of the diet has been altered, that the nutritional requirements in the two stages of growth are not identical and this is consistent with the evidence for considerable genetic independence as well. 7. It is proposed that the first stage of larval growth, which principally determines the duration of the larval period and may also influence body-size, is canalized. Genetic variation which can influence this stage is present in the population but contributes little to the phenotypic variation of adult size, except under special nutritional conditions as when ribonucleic acid is the sole limiting nutrient. But, at the same time, such canalization is dynamic in the sense that the absolute amount of growth which is completed in the first stage may vary with respect to diet and thereby lead to correlated variation in the duration of larval life and adult size. But individuals of an adapted population behave alike in this respect so that gene-environment interaction which leads to correlated variation in the two characters is of a very low order. 8. The canalized phase sets a limit to the potential growth in the later stage and thereby influences greatly the mean value about which such growth is equilibrated. This canalization plays a major role in the general stability of growth relations and body-size although this is normally concealed by the high level of phenotypic variation. This interpretation can account for a great variety of data and provides a rational guide to further analysis.

Selection for a threshold character in Drosophila I. An analysis of the phenotypic variance on the underlying scale

Abstract: The short-term response to artificial selection in a wild-type population for increased scutellar bristle number, has been interpreted in terms of two alternative threshold models. Both models have been shown to give a satisfactory transformation of the scale of measurement, in that the underlying variable shows an effectively linear response in terms of the accumulated selection differential, and the pheno-typic variance on the underlying scale remains virtually unchanged over a period of generations sufficient to increase the incidence of extra-bristles to almost 100%. A genetic analysis based on the bivariate model, which to a large extent takes account of the location of the supernumerary bristles, has shown the phenotypic variance on the underlying scale to have the following composition: the additive genetic variance is 27·2 ± 0·9% of the total, and the developmental error or ‘chance’ variance accounts for a further 63·8 ± 2·6%, so that the remaining 9·0 ± 2·7% of the variance must be due to environmental differences among individuals and to non-additive genetic effects. The relative magnitudes of these parameters are remarkably similar to those observed for two quasi-continuous variables in the same population, viz. abdominal and sternopleural hair number. In view of the ease with which scutellar bristles may be scored, the character can therefore serve as an extremely useful model character for quantitative genetic experiments.

Mi-spotted. A mutation in the mouse.

Abstract: Mi -spotted ( mi sp ) is a new mutation in the mouse at the microphthalmia ( mi ) locus. It has no obvious visible effect in either the heterozygote ( mi sp /+) or homozygote ( mi sp / mi sp ) and was discovered by virtue of its interaction with white ( mi wh ). Mice of genotype mi wh / mi sp are pale yellow with white spots; yellow areas later become ‘sooty’ at the first moult. Though mice of genotypes a / a ; mi sp /+ and a / a ; mi sp / mi sp cannot be visibly distinguished from those of a / a ; +/+, the amount of tyrosine-2-C 14 incorporated in melanin in skins of 5-day-old mice of these genotypes differed. Assays of tyrosine incorporation were extended to include other non-agouti genotypes differing only at the microphthalmia locus. The amount of tyrosine incorporated was greatest in +/+ followed in order by mi sp /+, mi sp /+, mi sp / mi sp , mi wh /+, mi wh / mi sp , and mi wh / mi wh . Pigment granules were examined in club hairs of these same genotypes for different regions of the hair shaft. Hairs of mi sp /+, mi sp / mi sp , and mi /+ could not be distinguished from +/+ either in number, kind or arrangement of granules. Hairs of mi wh /+ showed reduced cortical and medullary pigment, especially distally, which was even more pronounced in hairs of mi wh / mi sp . Medullary granules of mi wh / mi sp varied greatly in size with a few large yellow-brown granules.

Killing activity from lysed kappa particles of Paramecium

Abstract: Lysis of stock 7 killers with ½% sodium deoxycholate, yields preparations with one half as much killing activity as homogenates, while lysing virtually all of the bright particles known to have killing activity in homogenates. The killing activity which persists is associated with particles which sediment at the same rate as the refractile bodies, the only visible remnant of the bright particles. It is concluded that killing activity is probably associated primarily, if not exclusively, with the refractile bodies of the bright kappa particles. Partially purified killer particles when stored at 27° C. for more than one day, progressively lose their ability to produce spinning of sensitives but retain their ability to produce paralysis. Loss of activity in crude preparations of refractile bodies kept 2 hours at 31° C. can be retarded by homogenates of either killers or sensitives.

The effect of continued selection of phenotypic intermediates on gene frequency

Abstract: The selection of animals or plants for high values of a certain character may favour not only genotypes associated with these high values but also genotypes associated with high variability. Any differences between genotypes in variability may therefore be of considerable importance in plant and livestock improvement programmes as well as in evolution. The effects of various selection procedures on variability have been studied in three recent experiments [Falconer & Robertson (1956) Falconer (1957) and Prout (1962)]. In these experiments one line was continued by selecting, in each generation, parents with values of a particular character near the population mean. Manning (1955, 1956) has described the effects of this kind of selection applied to cotton. Robertson (1956) derived and discussed the theory of such selection procedures when certain simplifying approximations can be made We shall obtain some more general results and show that Robertson was incorrect in saying that the selection procedure would lead to gene fixation even if the heterozygotes are less variable than the homozygotes. The importance of the results is discussed in section 8.

Nutritional requirements of inbred lines and crosses of Drosophila melanogaster

Abstract: 1. The problem of whether or not hybrids are more efficient, less variable and have less stringent nutritional needs than their parents is examined by finding the dose-responses of four inbred Drosophila lines and their crosses to casein, choline, RNA, riboflavine, nicotinic acid, pyridoxine and folic acid, under germ-free conditions.2. Under more or less optimal conditions, survival, development rate and weight of the hybrids are generally superior to those of the inbreds; the 4-way cross is not inferior to the 2-way crosses. Variability of the crosses is not necessarily lower than that of the inbreds, and the 4-way cross is no more variable than the 2-way crosses.3. As measured by growth rate, the hybrids use casein more effectively than the pure lines, but their relative efficiency declines as the casein supply is decreased. There is a positive correlation between casein requirements for optimal growth and minimum requirements of pyridoxine. Hybrids also tend to be more efficient in their use of choline, but not of the other nutrients examined.4. Deficiencies of particular nutrients (and also of excess provision of the non-vitamins) affect the lines and crosses differently, so that their relationships to one another are altered. The hybrids show no special advantage in resisting departures from the optimum. Variability is also changed significantly under sub-optimal conditions and, in some situations, the hybrids may then be more variable than the inbreds.5. Each line and each cross is found to have its own optimal nutritional environment, and its particular reactions to departure from this. The full potential of the genotypes cannot be manifest, therefore, by tests in a single, standard environment.

The effect of dose-rate on the yield of translocations and dominant lethals following spermatogonial irradiation of mice

Abstract: 1. F 1 (CSH♀ × 101♂) male mice were given 1200 r. 60 Co Υ-irradiation over welve weeks and mated twelve weeks after the end of irradiation. The incidences of foetal and neonatal lethality and of semi-sterility in their offspring were compared with those in controls. 2. Embryonic survival to 15 days in the irradiated series was 98·2% that of controls, while the incidence of semi-sterility was 0·9% compared with nil in the controls. Neither of these differences is significant. 3. Comparison of these results with the significant rates of induction of dominant lethals and translocations in a previous experiment, in which a dose of 1200 r. acute x-irradiation was given to males of the same hybrid stock, show the existence of a dose-rate effect. Its magnitude cannot at present be accurately estimated. 4. The reasons for this effect are discussed. It is concluded that the main cause of the lowered translocation yield is that restitution of breaks will be favoured at low dose-rates, with less opportunity for the formation of interchanges. This could partly account for the lowered rate of induction of dominant lethals as well, but a full explanation is not yet possible.