1. By the use of intervarietal chromosome substitution lines, the poor crossability with rye (S. cereale, 2n = 14) of the wheat (T. aestivum, 2n = 42) variety Hope was shown to be determined by chromosomes 5A and 5B. The genes Kr1 and Kr2, which are responsbile for poor crossability (Lein, 1943), are probably located on chromosomes 5B and 5A respectively.

2. Crossability is actively inhibited by the dominant alleles, Kr1 and Kr2, of Hope and is apparently not enhanced by the recessive alleles, kr1 and kr2, of the readily crossable variety Chinese Spring.

3. The inhibition of crossability with rye conferred evolutionary and agricultural advantage upon wheat by preventing the production of sterile wheat-rye hybrids which could be regarded as weeds generated from within the crop.

A Mendelian population without artificial external constraints does in general not increase at a constant rate. Formulas neglecting the changes in population size introduce an error which is negligible under ordinary circumstances but whose cumulative effect over long periods may be disastrous. Questions relating to the cost of natural selection, the nature of an unstable equilibrium, the survival of genes, etc. cannot be treated without regard to absolute population sizes. The limitation of the notion of relative fitnesses is illustrated by the fact that in some typical situations the survival of the a-gene depends only on the absolute fitness of the Aa-heterozygote, but not on the fitnesses of the homozygotes. Furthermore, a decrease of the (absolute or relative) fitness of one genotype may actually increase the viability of the population and its ultimate size.

Even when the relative frequency qn of the a-gene tends to zero the absolute number of such genes may increase from generation to generation at a geometric rate. Therefore the circumstance that qn → 0 may be insignificant as compared to the fact that the earth cannot sustain an infinitely increasing population. Ultimately the population size is bound to influence the environment and so the fitnesses will change. Thus we must consider density-dependent fitnesses and then observed fitnesses cannot be used to predict the ultimate fate of a population. It is now known (Dobzhansky, 1965) that relative fitnesses are sometimes very sensitive to small changes in environment and that the same species may occupy a great variety of environmental niches. It is therefore quite likely that at least part of a population will find itself in a modified environment before too many generations have passed. For the evolution of a species and the development of new forms it is then not important that under fixed conditions the relative frequency qn of the a-gene would tend to zero. The problem is whether the actual number of such genes will increase for a period sufficiently long to encounter changed conditions or to establish itself in new combinations. This question is significant because the convergence of the frequencies qn to zero may be extremely slow. Thus even in a population of fixed size a disappearing gene could exist long enough to contribute to evolutionary processes.

Speaking generally, the thinking in terms of an assumed steady state and relative fitnesses seems to aggravate the problem of applying the wonderful results of modern genetics to the theory of evolution. For example, various mechanisms which are often considered as eliminating genetic variability may sometimes produce the opposite effect. The theory of evolution should distinguish between what the physicist would call macroscopic and microscopic equilibrium. Even if the world as we see it were in a perfect equilibrium this would not imply an approximate steady state for individual species, not to speak of genes. It is clear that an evolution to higher forms depends on a frequent decrease in fertility rates. If one considers slow changes rather than an unattainable steady state then a loss of fitness may be beneficial in the long run and contribute to genetic variety.

A Statistical analysis of the genome of D. melanogaster indicates that functionally related genes tend to be found on a particular chromosome and, when their locations within a given chromosome are measured in terms of map units, show a tendency to cluster; this clustering within chromosomes, however, is completely accounted for by the known clustering of all genes within chromosomes. Thus the analysis does not reveal any obvious functional significance for the arrangement of the genes within the chromosomes of this organism.

1. The linkage order of four tryA mutants of S. typhimurium, and cysB-12, is:

Attempts to plot the position of tryA-50 were unsuccessful.

2. Some of the reversions of tryA-8, tryA-47, tryA-56 and tryA-50 were analysed genetically; tryA-52 does not revert. All four auxotrophs gave reversions that were phenotypically and genetically indistinguishable from that expected by back-mutation of the original mutant site.

3. Both tryA-8 and tryA-50 produced reversions that grew as wild-type but were due to unlinked suppressor mutations. Some of these were super-suppressors in that they suppressed both tryA-8 and tryB-4; others suppressed many site mutants in the tryA gene but did not suppress tryB-4.

4. All the slow-growing reversions of tryA-8, tryA-50 and tryA-56, and a minority of the semi-fast reversions of tryA-8, were due to unlinked suppressors.

5. All the slow-growing reversions of tryA-47, the semi-fast reversions of tryA-56 and the majority of the semi-fast reversions of tryA-8 were due to genetic changes that were inseparable, in very extensive experiments, from their original mutant site.

6. Slow-growing reversions of tryA-47 produced faster growing mutants. Some of these were due to mutation in unlinked modifying genes and in others the genetic change was within the tryA gene. Nine of the latter had the genetic change just to the left of the 47S site; in one the change was inseparable from the 47S site. None had this further change to the right of the 47S site. These further changes, in the absence of the 47S site, gave prototrophic phenotypes; they are inter-site suppressors.

Oocyte pachytene analysis of embryos heterozygous for the fd translocation confirmed the facts of this translocation as described by Ohno and Cattanach. Besides that it revealed that a small piece of the X-chromosome has been transferred to the autosome where in about 25% of cases it shows less stainable expansion.

Analysis of the inheritance of the three bar-properties of bacteriophage T4: exclusion of T2 from the progeny of crosses, glucosylation of the hydroxymethylcytosine (HMC)moiety of the DNA according to T4, and plating with large plaques on E. coli K strains, was carried out by means of marker rescue from T4 by T2 on E. coli K (λh) as a selective indicator. Five of the strains isolated plated with large plaques on K (λh), but did not exclude T2 and showed T2 glucosylation; plating on E. coli K (λh) was found to segregate from the other two bar-properties. The sixth isolate showed, in addition to plating with large plaques on K, partial non-excludability by the parental T4 and T4 glucosylation of HMC. If partial non-excludability is the result of T4 glucosylation, the role of the additional glucose substitutions might be a protective effect on the DNA against the exclusion factor of T4. This proposal is supported by the analysis of the progeny from a single burst from a cross of T4 and T2. The following T2 genes were partially excluded: host-range, no exclusion of parental T2, sensitivity to ultraviolet, and limited plating efficiency on E. coli K (λh). The exclusion factor of T4 is not transmitted to all progeny and does not behave like a bar-property. Only resistance to exclusion and T4 glucosylation were transmitted to all twenty-seven progeny of the single burst. The elimination of sensitivity to exclusion and T2 glucosylation is explained by assuming that the recombinant class with the exclusion factor of T4 and T2 α-glucosylation will exclude itself and be suicidal upon infection of a new host. Exclusion and differential glucosylation are discussed with regard to restriction and modification, respectively.

An LT2 Hfr strain, his metC gal, was crossed to a multiply marked LT2 F− line. Analysis of recombinant yields, segregation of unselected markers and interrupted matings indicated injection of the Hfr chromosome in the sequence

The introduction into the Hfr of the colicine factors colI, colE1 and colE2 and the R factor R2 had little or no effect on its fertility. All four factors were transmitted at low frequency to the F− population, and to recombinants at higher frequencies (colI 5–30%, colE1 30–80%, colE2 5–30%, R2 0–9%). Transfer of colE1 occurred before 20 min., that of colE2 and colI later than 100 min. Segregation data did not reveal close linkage of any factor to any chromosomal locus, but recombinants with a long stretch of donor chromosome were more likely than others to have acquired colE2 and colI. Nearly all recombinants and F− cells which acquired colI or colE2 acquired both, and colE1 also. Most cells which acquired R2 acquired one or more colicine factors. These plasmid associations can be formally represented by transfer of plasmids, independently of the chromosome, in the sequence colE1—(colI, colE2)—R2. Phage P22 grown on the Hfr carrying the four plasmids transduced the tet-r trait of R2 at very low frequency, and the sul-r str-r characters, together, at low frequency. Some of each sort of drug-resistance transductant, but no transductants in respect of chromosomal characters, acquired colEl or colE2 by co-transduction.

Evolutionary factors which tend to decrease the mutation rate through natural selection and those which tend to increase the mutation rate are discussed from the standpoint of population genetics. The author's theory of optimum mutation rate based on the principle of minimum genetic load is re-examined, assuming that mutation rate is adjusted in the course of evolution in such a way that the sum of mutational and substitutional load is minimized. Another hypothesis is also examined that only selection toward lowering the mutation rate is effective and the present mutation rate in each organism represents the physical or physiological limit that may be attained by natural selection.

The possibility cannot be excluded that the spontaneous mutation rate is near the minimum that may be attained under the present mode of organization of the genetic material, and at the same time is not very far from the optimum in the sense of minimizing the genetic load.

Mutants of the Y locus differed appreciably in their basic conversion frequencies (frequencies of conversion in one-point crosses) to wild type. The differences in the basic conversion frequencies in the opposite direction, i.e. from corresponding wild-type allele to mutant, were in general not pronounced. For some alleles frequencies of conversion in both directions were similar, but for the others they differed markedly. No evident correlation between the position of mutants on the map and their basic conversion frequencies was observed.

In two-point crosses in repulsion, the great majority of recombinant octads were of conversion type. In these crosses symmetry or asymmetry of conversion depended mainly on similarity or differences in basic conversion frequencies of mutants crossed. In crosses between mutants from different clusters the recombination frequencies were near to the sums of their basic conversion frequencies. Such ‘mutant specificity’ makes it impossible to establish the linear order of mutants on the basis of recombination frequencies in two-point crosses.

The results of two-point crosses in repulsion between mutants within clusters pointed to the influence of one allele on the frequency of conversion of another one. This ‘marker effect’ was also evident in some three-point crosses.

The frequencies of simultaneous conversions in two-point crosses in coupling did not show negative correlation with the distances between the mutants involved.

It seems that many of the data presented here are most easily explained by recently developed hybrid DNA models.

Nineteen axial skeletal variants are described in the frog Rana cyanophlictis, collected from five isolated populations of Delhi. Four of these populations came from large perennial ponds and one, a transitory population, was entrapped from a temporary rain pool. The populations were found to diverge significantly from each other in the incidence of these skeletal variants. We have attributed this divergence to genetic drift, but the effects of unknown selective forces cannot be ruled out.

The isolation and characterization of an isogenic series of twelve Hfr strains is described. From their points of origin it was concluded that the sex factor integrates at a limited number of sites on the bacterial chromosome. Although the nutritional requirements of these Hfr strains were similar to those of the parent F+ strain, it was observed that one group had a markedly slower growth rate. The relevance of these observations to theories on the nature of F+ fertility and on the formation of Hfr strains is discussed.

1. A number of stable nystatin-resistant mutants of the yeast Saccharomyces cerevisiae have been isolated from platings of a sensitive wild-type strain on low concentrations of the antibiotic.

2. These mutants were found to be resistant to 10, 15 or 60 units of drug/ml.

3. Analysis of meiotic segregants from crosses of these mutants to wild-type indicate that resistance is determined by two types of genes; resistance genes and modifiers.

4. Functional analysis of the mutants demonstrated the existence of three recessive resistance genes, nys-l, nys-2 and nys-3 and that nys-1 and nys-2 were linked.

5. Genetic analysis showed that nys-1 was affected by two modifiers, Mnys-1 and Mnys-2, but that only Mnys-2 affected nys-2 and nys-3.

6. The modifiers Mnys-1 and Mnys-2 are dominant.

7. An investigation of the effects of temperature and medium on resistance demonstrated marked interactions between genotype and environment for both the resistance genes and the modifiers.

8. Second-step mutants have been isolated by plating first-step mutants on higher concentrations of the drug. Some of these are resistant to 800 units/ml.

9. Some possible mechanisms of nystatin resistance are discussed.

Parameters necessary for predicting direct and correlated responses for large and small 13-day larval weight in T. castaneum on two levels of nutrition were estimated in the base population. Larval weight in the GOOD environment was approximately twice that observed in POOR. Heritabilities (estimated from the ratio of sire component to total phenotype variance) of larval weight on the two rations were similar, 0·21 ± 0·06 and 0·19 ± 0·05 for GOOD and POOR, respectively. Heritabilities based on dam-offspring covariances were similar to these, but those obtained from full-sib covariances were much larger (0·97 ± 0·07 for GOOD and 0·69 ± 0·07 for POOR). This suggested that considerable dominance rather than maternal effects were present. The genetic correlation between growth on GOOD and growth on POOR was estimated as + 0·60 ± 0·21.

The selection experiment was replicated four times with each replication extending over eight generations. Good agreement between predicted and observed values for direct selection was observed for large selection in both environments and small selection in POOR. However, response to small selection in GOOD was significantly greater than predicted in all four replications and was associated with increased selection differentials. Realized heritabilities were approximately the same for both directions in GOOD yet asymmetrical responses occurred for all replications due to unequal selection differentials. On the other hand, realized heritabilities were asymmetrical in POOR. Those observed for small selection were more than twice the size of those calculated for large lines. However, the responses in POOR were symmetrical since the selection differentials varied inversely with the realized heritabilities.

Because of the asymmetry observed for heritabilities and selection differentials, correlated responses were poorly predicted. The average effective genetic correlation between growth in GOOD and growth in the POOR environment agreed remarkably well with the base estimate, yet asymmetry of the genetic correlation was a consistent phenomenon with values for the large lines being less than the base parameter while small lines were uniformly larger.

Asymmetries of the various genetic parameters were not anticipated from base estimates. They were not caused by sampling or chance fluctuations since all four replications were remarkably consistent. Asymmetry for any one genetic parameter (e.g. heritability) was associated with a particular environment or direction of selection while other genetic parameters reacted asymmetrically in populations exposed to a different set of environmental treatments.

For maximum performance in a single environment, these results show that selection should be practiced in that environment. With regard to mean performance in GOOD and POOR environments, selection for large size in POOR gave some 25% more gain than selection in GOOD. Selection for small size in either environment was equally effective in obtaining minimum size in both environments.

Crossing-over between the α and the β loci constituting the A incompatibility factor gives rise to two new specificities which are compatible with both parental As and with each other. The frequency of monokaryotic mycelia carrying re-combinant A factors is shown to be under genotypic control in a multiple crosses programme (6 × 6), selection for high and low recombination frequencies (two generations), and crosses between the selection lines. The recombination values based on samples of 100 monokaryons, range from 0 to 21%; however, the more accurately estimated values of the ‘High’ and ‘Low’ selections are 14% and 4%, each being based on approximately 2,000 mycelia.

The data are compatible with a gene-system consisting of the postulated locus rec which has a major effect on recombination and which is linked to the A factor, and several minor effects by other loci. Alternative interpretations are presented and discussed. The apparent dominance of low frequencies of recombination on high frequencies can be related to the breeding behaviour of S. commune. Thus close linkage between α and β allows a high number of A specificities to be maintained in a population as well as high out-breeding potential, while the inbreeding potential (i.e. dikaryotic combinations between monokaryons originating from a single fruit-body) is kept low and near its minimum.

The significance of the two-locus structure of the incompatibility factors is examined theoretically in an Appendix at the end of the Discussion section.

Maps have been made showing the order of am mutant sites using (a) frequencies of am+ recombinants from crosses between am mutants and (b) the modes of distribution of the am+ recombinants among the two parental and two recombinant classes with respect to the flanking markers inos and sp.

It is possible to arrange the sites in an order such that, in almost all the crosses yielding useful numbers of am+ recombinants, the sp allele originally in coupling with the distal am mutant site occurs in the majority of the recombinants. No such consistent pattern was found with respect to the inos marker. The order obtained by reference to sp agreed with the best order deducible from recombination frequencies.

The data are consistent with the hypothesis that am+ recombinants arise by a process of gene conversion, that there is a gradient of conversion frequencies from the right (inos or distal) end of the gene to the left (sp or proximal) end, and that conversion tends to be associated (though less than 50% of the time) with crossing-over, especially on the distal side.

There is no obvious relationship between the map position of a given am mutant and the properties of the protein product of the mutant gene.

1. By means of tetrad analysis three vitamin-requiring mutants have been established as markers of centromeres distinct from those of the two known chromosomes.

2. Mutants existing in stock were tested for linkage with these centromere markers, and four previously unknown linkage groups with independent centromeres thereby established and accurately mapped.

3. Corrections were made to the maps of existing linkage groups. The A locus (Group I) was shown to be approximately four times as distant from its centromere as hitherto supposed (at least in most crosses); and several markers of Group II were mapped for the first time.

Reports of sex differences in crossing-over in animals, published since Haldane in 1922 suggested that crossing-over should be less frequent in the heterogametic sex, have been reviewed and discussed. No general rule is discernible apart from the absence of crossing-over in males of the dipteran genera Drosophila and Phryne and in females of some lepidopteran species, due apparently to failure of chiasma formation in the heterogametic sex. In the majority of animal species examined crossing-over occurs in both sexes. While there is some tendency in mammals for crossover values in females to exceed those in males, it was of greater interest to find that marked sex-differences occur in the same species (data chiefly from the house mouse) in opposite directions in different chromosomes. The influence of factors acting locally in the chromosomes, such as those associated with hetero-chromatin, were indicated as promising subjects for the study of variations associated with sex.

(a) Coprinus lagopus has in nature both a monokaryon with one haploid nucleus per cell and a dikaryon with two haploid nuclei per cell. It also has in experiment both a heterokaryon with two types of nuclei distributed irregularly in the mycelium and a diploid monokaryon with one diploid nucleus per cell.

(b) Two pairs of linked recessive auxotrophic mutants, me-5 ad-8 and adhis-1 chol-1 have been combined in two different sets of multiple heterogenotes so that in the dikaryon and heterokaryon the + (active) alleles of the four genes are distributed equally in the two component nuclei. In one combination the linked genes are in trans and in the other they are in cis arrangement in diploid, dikaryon and heterokaryon.

(c) Complementation between the + genes, as measured by growth on minimal and complete media, was complete in the diploid and dikaryon but was only partial in the heterokaryon.

(d) A similar comparison of a recessive suppressor of the mutant me-1 revealed that the recessive gene was not expressed and therefore was fully recessive in the diploid and dikaryon but was only partially recessive in the heterokaryon.

(e) The exact similarity of complementation of the structural genes of the auxotrophic mutants and the recessiveness of the me-1 suppressor in diploids and dikaryons exclude a localization of gene interaction in the nucleus. In a heterokaryon cytoplasmic dilution of the product of a dominant gene can occur and has the effect of producing a phenotypic difference between heterokaryons and diploids.

1. Lines with ten pairs of parents and selected at an intensity of 20% were exposed to 1000 r. of X-rays for 0, 2, 10 or 30 generations.

Lines which received some irradiation generally gave greater response than the unirradiated controls. The phenotypic variance in the irradiated lines was much higher than in the controls. There was little difference in behaviour between lines receiving ten generations of irradiation and those irradiated every generation. Lines receiving only two generations of irradiation had lower variances than the other irradiated lines, but in one of three replicates the response was greater than the corresponding continuously irradiated line.

3. Lethal frequencies were much higher in irradiated than unirradiated lines. Particular chromosome II and III lethals were at high frequencies in most of the irradiated lines but in only two out of five controls.

4. On relaxation, the mean of the irradiated lines generally declined considerably, but in the unirradiated lines there was only a very small regression.

5. It appears that most of the extra response and increased variance in the irradiated lines were caused by a few genes with large effect on bristle number.

1. Four lines selected for large size were crossed to form a base population for further selection for high 6-week weight; three small lines were crossed similarly, and the crossbred population was selected for low 6-week weight.

2. In every case, a cross between two selected lines resulted in heterosis increasing body weight. This shows that all of the selected lines were differentiated with respect to genes affecting body weight.

3. Further selection for large size produced a stock whose mean weight was 25% higher than the largest of the original lines at its limit. But the response to selection for small size was slow, and after twenty-four generations of selection, the low weights of two of the original lines had not been recovered.

4. The evidence points to linkage of genes affecting body weight in the mouse. It is suggested that this is a particular feature of crosses between previously selected lines, rather than a general feature of mouse populations.