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Sixty-two mutants of E. coli K-12 resistant to 40 μg./ml. valine were isolated from a sensitive strain. Transduction experiments using phage P1 showed that one group of these mutants, val-r-C, is closely linked to leu, another group, val-r-B is closely linked to thr, and a third mutant, val-r-D57, lies between leu and thr. Conjugation experiments showed that the remainder of the mutants could be divided into three groups, val-r-A, val-r-E and val-r-F on the basis of their different times of transfer from Vhf donors to val-s F− recipients. All the mutants are sensitive to 10,000 μg./ml. valine; val-r-B and val-r-D mutants are resistant up to 80 μg./ml. valine; val-r-C mutants are resistant up to 1000 μg./ml. valine, and val-r-A, val-r-E and val-r-F mutants up to 5000 μg./ml. The functional significance of the genetic locations of these groups is discussed.
In mutants at the ‘bristle’ locus of Aspergillus nidulans the conidiophore remains as a stiff hypha rather than developing a vesicle, sterigmata and conidia. The brlA 12 allele of this locus has a variegated phenotype, and genetic analysis has shown that this is associated with a translocation which has a breakpoint in the map interval adjacent to the bristle locus.
The mutant phenotype is partially repaired on high-salt medium at low pH, and can also be repaired by suppressors, one of which has been mapped at a locus unlinked to brlA 12.
The mutant provides proof that variegation is due to instability of gene expression and not to mutability since brlA 12 is genetically stable and can be propagated from either conidia or sterile conidiophores, the structures formed at the two extremes of variegation, and the resulting colonies in both cases are identical to the original strain.
It has been shown by mitotic recombination that the translocation associated with the variegated mutant is a ‘simple translocation’ in which the distal half of linkage group VIII is attached to the end of linkage group III. This terminal attachment site does not appear to be damaged in any genetically detectable way.
Models of two linked overdominant loci in moderately large, but finite, populations are examined by looking at the variance-covariance matrix of the two gene frequencies and the linkage disequilibrium around stable deterministic equilibrium points. In particular, the effect of genetic drift is examined in cases where, in infinite populations, two stable equilibria with non-zero linkage disequilibrium, D, are maintained. Theoretical formulae are produced and checked by computer simulation. In general, the results show that unless the population size is very large indeed, genetic drift causes the values of D to vary considerably about the equilibrium values and that for many models, where stable equilibria exist at non-zero D values, a wide range of values of D have a high probability. Thus it is very difficult to draw conclusions about the selection regime by measuring Linkage disequilibrium in a finite population.
The inheritance of three lymph protein fractions separable by starch-plate electrophoresis has been studied. Each fraction is under the control of a separate gene, the dominant allele determining its presence and the recessive its absence.
The gene for the fastest fraction is sex-linked, whilst those for the other two are autosomal and linked.
The third chromosome mutant, hairy1, adds a varying number of microchaetae to the scutellum. The genetic relationship between this character and scutellar bristles was investigated using the conventional techniques of full- and half-sib analysis of variance and covariance, direct and correlated response to selection for microchaetae and scutellars respectively and diallel crosses at two stages in the programme. There was a good correspondence between the predicted and realized divergence resulting from selection for increased and decreased microchaetae. The correlated response in scutellar bristles appears to be accounted for primarily by genetic changes in microchaetae.
In a population under artificial selection, the effective population size may be less than the actual number of parents selected because there will be variation between families in the character under selection and consequently in the probability of selection. Expressions are developed for the magnitude of the effect, which will be greater the more intense the selection and the higher the heritability of the selected character. The inbreeding due to outstanding individuals may rise for several generations after their use.
1. Approximately 25000 mice have been produced over twelve generations of selection in nine lines. The experimental design involved a 3 × 3 factorial arrangement of direction of selection with mating system. The primary character measured was 6-week body weight.
2. Consistently high phenotypic correlations between mates have been achieved, positive in the assortative lines, negative in the disassortative lines. Correlations were low and inconsistent in direction in the random-bred lines. These correlations have had very little, if any, effect in redistributing the genetic variance as estimated from the variance component analysis; the expected higher variances in the assortative lines and expected lower variances in the disassortative lines have not appeared, thus leaving heritability unaffected.
3. Selection differentials likewise show no consistent advantage for the assortative lines, so that the progress from selection has been virtually identical in all three mating systems in each direction.
4. Assortment of mates, either positively or negatively, for characters of even moderate heritability appears to have little influence on the outcome of selection. On the other hand, selection has been singularly effective in modifying the mean 6-week weight, with progress markedly greater in the downward direction; indeed it appears that the lower limit, may already have been approximately attained.
5. Environmental effects operating in the various generations have affected all lines in remarkably consistent fashion.
The influence of the linkage group II locus y on DDT resistance in Aedes aegypti has been studied in crosses between the Trinidad resistant strain and QS susceptible strain. The y locus influences DDT resistance in both R/R and R/+ larvae. The effect of y may be interpreted as reducing the penetrance of R (RDDT1), which is also located on linkage group II. y+ is partially dominant and incompletely penetrant in its resistance-enhancing role (although in its pleiotropic effect on larval colour it is dominant and fully penetrant). Penetrance of y+ is influenced by an environmental factor, probably associated with the larval diet.
The effect of y on resistance is evaluated in relation to other genetic influences on the expression of RDDT1.
The significance of polymorphism at the y locus is discussed.
Rice, Cloninger & Reich (1980) showed that correlational data on American I.Q. is consistent with a rather low genetic heritability. Here we confirm their general results with a more parsimonious model. From phenotypic data alone, the estimates of genetic and cultural heritability are 0·31 and 0·42, respectively. Using environmental indices, the parsimonious estimates become 0·34 and 0·26, respectively.
I + × I + crosses were studied, using various Coll plasmids. Exclusion due to presence of Coll in recipients was removed by starvation, with production of I – phenocopies. Superinfection immunity prevented normal replication of transferred genes: thus, Itrp + donated to an I + trp– recipient led to formation of abortive recombinants.
The effects of population size and selection intensity, which are in the breeder's control, are investigated for ranges of values of quantities outside his control, namely the number, initial distribution of frequencies and effects of genes influencing the trait. Two alleles are assumed to be initially segregating at each locus, with no linkage, dominance or epistasis. The effects are assumed to follow a gamma distribution, using a wide range of its two parameters which specify both mean gene effect or selective value and the shape of the distribution, or the ratio of Wright's effective number to actual number of genes. The initial gene frequencies (q) are assumed to be either 0·5 at all loci, uniformly distributed over the range 0–1, or to have a U-shaped distribution, proportional to [q(1 − q)]−1 such as derives from neutral mutation, with gene effect and frequency distributions independent. The mean and variance of selection response and limits, in the absence of new mutation, are derived.
The shape of the distribution of effects is not usually important even up to the selection limit. With appropriate parametrization, the influence of the initial frequency distribution is small over a wide range of parameters. For reasonable choices of parameters, the effects of changing population size from those typically used in animal breeding programmes are likely to be small, but not negligible. For the initial U-shaped frequency distribution, further increases in population size are always expected to give a greater limit, regardless of present value, but not for the other distributions.
A null allele of the Gpi-1s structural gene, that encodes glucose phosphate isomerase (GPI-1; E.C. 5.3.1.9), arose in a mutation experiment and was designated Gpi-1sa-m1H. The viability of homozygotes has been investigated. No offspring homozygous for the null allele were produced by intercrossing two heterozygotes, so the homozygous condition was presumed to be embryonic lethal. Embryos were produced by crossing Gpi-1sa/null heterozygous females and Gpi-1sb/null heterozygous males. Homozygous null embryos were identified at different stages of development by electrophoresis and staining either for GPI-1 alone or GPI-1 plus phosphoglycerate kinase (PGK) activity. At 6½ and 7½ days post coitum homozygous null embryos were present at approximately the expected 25% frequency (37/165; 22·4% overall) although at 7½ days the homozygous null embryos tended to be small. By 8½ days most homozygous null embryos were developmentally retarded and had not developed significantly further than at 7½ days; some were dead or dying. By 9½ days the homozygous null conceptus was characterised by a small implantation site that contained trophoblast and often a small amount of extraembryonic membrane. Surviving trophoblast tissue was also detectable at 10½ days. Previous studies have shown that oocyte-coded GPI-1 persists only until 5½ or 6½ days. Survival of homozygous null embryos to 7½ or 8½ days and survival of certain extraembryonic tissue to 10½ days suggests that the homozygous null condition may not be cell-lethal although it is certainly embryo-lethal. Mutant cells that are deficient in glycolysis may use the pentose phosphate shunt to bypass the block in glycolysis created by the deficiency of glucose phosphate isomerase, and/or might be rescued by the transport, from the maternal blood, of energy sources other than glucose (such as glutamine). Either strategy may only permit slow cell growth that would not be adequate to support normal embryogenesis. Transport of maternal nutrients would be more efficient to the trophoblast and extraembryonic membranes and this may help to explain why these tissues survive for longer than the embryo itself. The morphological similarity between homozygous nulls and androgenetic conceptuses, where the trophoblast also survives better than the embryo, is discussed.
A variety of Klebsiella strains examined all show either a strong (ML+) or a weak (ML−/+) lactose-positive phenotype on MacConkey agar. ML+ Klebsiellae have about 10 times the β-galactosidase activity of ML−/+ strains in cultures both induced and not induced for this enzyme. Of 14 ML+ strains of diverse origin tested, at least 13 carry a lac operon on a plasmid which can be transferred to Escherichia coli. The seven plasmids so far studied in detail all belong to the F compatibility group but are unable to promote their own transfer. To explain these results it is suggested that the Klebsiella group derive from a common ancestor with a chromosomal lac operon of low efficiency, which was made good by the acquisition of a lac operon from another bacterial strain, probably E. coli: the new lac genes remained as a plasmid, possibly because they could not be integrated in the new host.
Tenebrio molitor satellite DNA has been analysed in order to study sequential organization of tandemly repeated monomers, i.e. to see whether different monomer variants are distributed randomly over the whole satellite, or clustered locally. Analysed sequence variants are products of single base substitutions in a consensus satellite sequence, producing additional restriction sites. The ladder of satellite multimers obtained after digestion with restriction enzymes was compared with theoretical calculations and revealed the distribution pattern of particular monomer variants within the satellite. A defined higher order repeating structure, indicating the existence of satellite subfamilies, could not be observed. Our results show that some sequence variants are very abundant, being present in nearly 50 % of the monomers, while others are very rare (0-1 % of monomers). However, the distribution of either very frequent, or very rare sequence variants in T. molitor satellite DNA is always random. Monomer variants are randomly distributed in the total satellite DNA and thus spread across all chromosomes, indicating a relatively high rate of sequence homogenization among different chromosomes. Such a distribution of monomer variants represents a transient stage in the process of sequence homogenization, indicating the high rate of spreading in comparison with the rate of sequence variant amplification.
A model of the balance between mutations and stabilizing selection affecting a quantitative character is developed and analysed. This model is essentially a discretized version of the continuum-of-alleles models analysed previously by Kimura, Lande, Turelli and others, and is formally similar to the stepwise mutation models used to interpret electrophoretic data. The complete model cannot be solved even for a haploid species, but there are useful approximations for most parameter values of interest. The ‘house-of-cards’ approximation can be used when selection is strong relative to mutation, and a normal approximation can be used when selection is relatively weak. For intermediate levels of selection a new ‘five-allele’ approximation provides accurate results over a wide range of parameter values. The house-of-cards and five-allele approximations applied to recessive alleles in a diploid population show that, for a given mutation rate, a somewhat larger genetic variance is maintained at equilibrium than in a comparable model of additive alleles. Under directional selection, the increase in genetic variance is largest for alleles of large effect and is much smaller for alleles of intermediate or small effect. At an equilibrium under stabilizing selection, homozygotes would tend to have a higher average fitness than heterozygotes when each mutation has a relatively large effect (the house-of-cards approximation), with the reverse if each mutation has a small effect (the normal approximation).