The analysis of the variation in the mutation rate in the fractionated progeny of treated males, revealed a marked differential cell stage response to the various chemical series investigated. The mustard derivatives of amino-acids (particularly L-phenylalanine) exert their minimal mutagenicity on mature sperm, but possess an appreciable activity on other stages of spermatogenesis, including spermatogonia. The carboxylic-acid mustards produce their maximal effect on an early spermatid, but are practically ineffective on spermatocytes and spermatogonia. The amine mustard corresponding to the phenylalanine derivative is effective on the stages of spermiogenesis (including the early spermatids) as well as on the spermatocytes, but is inactive on the spermatogonia (at least the primary stages). The response of the gonia, therefore, is a function of the amino-acid moeity of the mutagen, and is not merely due to the presence of an amino-group in the molecule.

The name zigzag has been given to an inherited behaviour defect in the mouse in which the animals walk with a zigzag motion. It is inherited polygenically. The anatomical defect responsible for the abnormal behaviour was a reduction or absence of the horizontal canals of the inner ear, the reduction consisting of a constriction in the middle of the canal length, rather than a shortening of the canal.

1. The earliest manifestations of the gene for syndactylism discovered include hyperplasia of the apical ectodermal ridge of the limbs and hyperplasia of parts of the limb epidermis (10–10½-day stage). Somewhat later, a similar hyperplasia of the epidermis in the distal parts of the tail is found in some sm/sm embryos.

2. Enlargement and deformation of the foot plates in both fore and hind limbs is present in the 12-day stage; in the fore limbs it probably starts on the preceding day. The foot plates are bent over in a palmar or plantar direction respectively; the crowding together of the middle digits thus produced is the mechanical cause of syndactylism.

3. It is suggested that the enlargement of the foot plates with the ensuing deformities is due to increased stimulation of mesenchymal growth by the hyperplastic apical ectodermal ridge. On this interpretation, all the skeletal effects (including those in the tail) are secondary to a systemic tendency to epidermal hyperplasia.

4. The hyperplastic regions of the apical ectodermal ridge and of the limb epidermis start to keratinize (parakeratosis) in the 13-day stage whereas in normal development keratinization of the skin does not start until some 3 days later.

A long-established laboratory stock was found to contain many individuals that were heterozygous for a lethal gene, called tailless-Edinburgh (te). Heterozygotes are indistinguishable from normals except by breeding tests with special tester stocks supplying brachyury (T) gametes, when tailless (Tte) progeny distinguish carrier parents from normal parents that produce only short-tailed (T +) progeny. When males are mated to tester females providing brachyury eggs, the ratio of Tte: T + progeny reflects the ratio of te: + spermatozoa. The proportion of te spermatozoa measured in this way led to the expectation that 62% of individuals in the original stock would be carriers, whereas 80% was found. Independent evidence is presented for + te males that the incidence of te in their effective spermatozoa was higher when normal eggs were fertilized in matings within the original stock than when brachyury eggs were fertilized in outcross matings to the tester stock. These observations suggest that the proportion of te spermatozoa partaking in fertilization was modified by the genotypes of the females or of their eggs.

Advantage was taken of a unique situation to test, with adequate controls, the assertion that male and female gametes conjugate at random. The data concern the aberrant locus T of the mouse, at which there are a number of t alleles that enter into the majority of effective spermatozoa of males heterozygous for one of them. Segregation in females is normal. Evidence is presented for one of these t alleles, tailless-Edinburgh (te), that conjugation between gametes was not at random when this gene was present in spermatozoa. When a choice of eggs was presented by heterozygous females, tailless-Edinburgh spermatozoa united more frequently with normal than with brachyury eggs and more frequently with brachyury than with tailless-Edinburgh eggs. The relevance of this finding is discussed in relation to expected equilibria of t alleles in closed populations. Other forms of selective fertilization are discussed and their genetic consequences compared.

1. The experiment was designed to provide basic information relevant to the utilization of heterosis in animal improvement. The character studied was the size of the first litter in mice.

2. Thirty inbred lines were crossed at random when the inbreeding coefficient reached 0·50 (three full-sib matings). The lines had been inbred without selection except for natural selection operating with lines.

3. The mean litter size of the crossbred mice did not exceed that of the outbred population from which the inbred lines had been derived. This indicates that the increased litter size normally associated with crossbred mice must be ascribed to some form of selection other than within-line natural selection.

4. Estimates were obtained of the variance components associated with general and special combining abilities. As anticipated, these estimates were very small, especially those relating to special combining ability. Before selection between crosses becomes possible, high levels of inbreeding must be achieved.

Some anomalous results are described of genetical tests using the sex-linked markers Tabby and Bent-tail. The results are shown to be consistent with the demonstration by Welshons & Russell (1959) that the X/O chromosome constitution is female, and suggest that the condition can arise from non-disjunction in the female as well as from non-disjunction in the male parent. A single animal of presumed X/X/y constitution appeared anatomically to be fully male, but died before breeding test could be performed.

1. A random bred population of mice was subjected to inbreeding and the changes of litter size, measured as the number of live young in first litters, were followed.

2. The mean litter size declined at a rate of 0·56 young per 10% increase of the inbreeding coefficient.

3. Selection for large litters within the lines during the inbreeding did not effectively reduce the rate of decline.

4. Out of twenty lines at the beginning of the inbreeding seventeen were lost by the time the inbreeding coefficient reached 76%. Two more were lost later and one survived indefinitely. The three lines that survived longest started at a level below the mean and did not decline in litter size. The one that survived indefinitely reached 99% inbreeding without dropping below the non-inbred control.

5. The three lines surviving at 81% inbreeding were crossed and the litters produced by the crossbred progeny were larger than the non-inbred control by about two young per litter. This gain from heterosis is attributable to selection among the lines on their performance as inbreds. A second and third cycle of inbreeding and crossing yielded no further progress, and the level of the first cross was never regained. This is attributable to the ineffectiveness of the selection applied and to the previous restrictions of the population size.

6. The behaviour of the lines in the inbreeding and crossing point to simple dominance rather than over-dominance at the loci causing variation of litter size.

7. This experiment suggests that, as a means of improvement of farm animals, cyclical inbreeding and crossing does not look very hopeful.

Two mosaic birds are described, from a sex-linked F1 cross (Rhode Island Red ♂ × Light Sussex ♀). They are sexually normal males and full brothers. Each has the following abnormalities on one side of the body: absence of the maternal dominants S (silver, sex-linked), W (white skin) and Co (Columbian restriction of black), and reduction in size. In one case all the melanocytes appear to be derived from the smaller side, so that the plumage pattern is identical on the two sides; in the other there is a minor deviation (modified expression of Co) from normal F1 plumage pattern on the larger side. Mated to Brown Leghorn hens, both mosaics bred as normal F1 males, with no evidence of germinal mosaicism. Over thirty full sibs were all found to be normal.

A purely paternal origin of the smaller side appears to be excluded in both cases by the lack of striping in the down, and by minor deviations from normal Brown Leghorn phenotype in adult plumage pattern. Origin by some kind of maldistribution of chromosomes at first cleavage division would require the X-chromosome and possibly as many as three autosomes to be affected simultaneously.

Two further unrelated crossbred mosaic males are described. Each has yellow skin (w) on one side of the body. In one case this is accompanied by a slight difference in plumage pattern, reduction in size and abnormal proportions in the limb bones; in the other merely by a slight reduction in size. Loss or non-disjunction of a single chromosome at first cleavage division is a possible explanation of these.

1. The interrelations between environment and the phenotypic expression of genetic differences have not received the attention they merit. Laboratory studies in quantitative inheritance, either by choice of character or experimental conditions, have not shed much light on this problem. Selection for the same character in different environments is likely to involve qualitative differences in physiology and development. Comparative study of such changes will throw light on the genetics of development generally, which in turn is relevant to how far the selection response can be pushed in a given direction. Since statistical variation between individuals must ultimately be interpreted in biological terms, the unnatural barriers between quantitative and physiological genetics must be broken down to clear the way for a greater variety of experimental analysis and a more widely based approach to the interpretation of individual differences in populations. The ecology of the animal provides the point of departure and guide to the kind of environmental variation which should be studied first. Since the suggested approach cuts across the conventional limits of quantitative, physiological and population genetics and exploits the concepts and methods of these alternative approaches to a common end, it is convenient to have a descriptive label. The term ‘ecological genetics’ has been adopted.

2. This introductory paper is the first of a series dealing with experiments orientated along these lines. Since environmental variation largely consists of variation in the quantity and composition of the diet, the growth of individuals from a cage population of Drosophila melanogaster and also other strains has been studied on a variety of aseptic, synthetic diets. Body size and duration of the larval period are taken as measures of growth. There is a well-marked ability to regulate body size, by extending the duration of development, provided the diet is not too deficient. When the diet is further reduced development time is further lengthened and body size is reduced as well.

3. To test for genetic differences in reaction to the diet, strains have been created by selecting for large or small body size, and their performance, together with that of the cross between them, has been compared with the performance of unselected individuals on alternative diets for the first few generations of mass selection. There is evidence of gene-environment interaction quite early in selection, and after six generations striking differences were detected. It is concluded that genetic differences in reaction to different sub-optimal diets are widespread in the population.

4. The within-culture variance is increased by growing larvae on progressively more deficient diets and is approximately twice as great on a low-protein diet as on the usual live yeast medium. This increase is attributed to the segregation of genetic differences which are unimportant and contribute little to the variance under more favourable conditions.

5. Comparison of body size and development time in repeated tests with two diets lacking fructose or deficient in ribonucleic acid revealed evidence of a plasticity of response to minor nutritional variation which is characterized by a positive association between body size and the duration of the growth period. This relationship is the reverse of that associated with crude variation in the diet which leads to a negative association between development time and body size. This plasticity of response probably represents an aspect of physiological homeostasis. Genetic differences in the magnitude and direction of this response probably contribute to gene-environment interaction generally, and this probably accounts for apparent discrepancies in alternative estimates of the response to selection for large and small body size when these are based on deviations from the unselected. This suggests the need for determining how far body size may be increased either by altering the growth rate or by extending the growth period, and also how far strains differentiated in such respects differ in their reaction to controlled differences in nutrition.

1. Strains from a cage population of Drosophila melanogaster were selected for increased body size on the live yeast medium and on two aseptic synthetic media, (1) deficient in protein and (2) with all nutrients reduced to one-third the normal concentration required for growth to normal size. Both these media reduce body size by about 25%.

2. In two strains, mass selected on the live yeast medium, the response continued fairly steadily for at least sixteen generations, when the experiment was discontinued. By this time body size had been increased by some 30%.

3. On the sub-optimal diets the number of selected parents per generation was twice as great as on the live yeast medium, for technical reasons, but the response ceased abruptly after seven or eight generations of selection at a level considerably below that attained by the strains selected on the more favourable diet. Also, when selection was continued on the live yeast diet, no further progress occurred.

4. Flies selected on the different diets and also unselected flies have been grown on the alternative conditions to see how the deviation from unselected is affected. For both strains selected on sub-optimal diets, the deviation from unselected is appreciably greater on the medium used for selection than on the live yeast medium.

5. The response to selection for larger body size on deficient diets can be attributed partly to better adaptation to these conditions. This inference is supported by several lines of evidence. The within-culture variance, which is clearly greater when selected flies are grown on deficient diets, declines with effective selection. Also in the low-protein strain, for which data are available, the duration of the larval period is shortened in the early stages of selection, while egg production considerably exceeds that of unselected flies grown on the same diet.

6. Other effects, of the kind normally selected for on the live yeast medium, also contribute to the variation and selection response on the deficient diets. At first they appear to act more or less independently of the genetic changes which favour increased size via improved adaptation to the diet, but continued selection soon leads to mutual incompatibility between the alternative pathways in growth. Since no further progress occurred when selection was continued on the live yeast medium, the earlier selection had probably lowered the level of adaptation to the live yeast medium. A new genetic situation had been created in which it was impossible to gauge the amount of further progress by reference to the behaviour of strains selected on the live yeast medium from the beginning.

7. Estimates of heritability, based on cumulated selection differentials, are rather similar in the different diets and range between 0·30 and 0·38. On the live yeast medium, the estimate provides a fair guide to future progress, whereas, on the deficient diets, the predictive value is nil since response ceases immediately after the generations which provide the data for the estimates.

8. By comparing the deviation from unselected on the media used for selection and also the other media, alternative estimates of genetic correlation in performance in different conditions can be computed. The estimates were sufficiently divergent to cast doubt on the practical utility of the statistical procedure, which takes no account of the likelihood that individual variation in body size in different environment represents to greater or lesser degree the effects of segregation on different processes of growth and metabolism.

9. Since the course of selection is influenced by nutritional conditions, comparisons of response to selection for the same ‘character’ such as body size, in populations or species adapted to different conditions, must allow for the likelihood that unequal differences between the conditions in which selection is carried out and those in which the animal normally lives may be an important cause of differences in response.

The American raspberry variety Chief is shown to carry three dominant genes, A5, A6 and A7, each capable of conferring strong resistance to Amphorophora rubi strain 1.

Chief also carries three genes, A2, A3 and A4, for resistance to A. rubi strain 2. A2 is a dominant gene conferring full resistance by itself; A3 and A4 are dominant complementaries, neither gene by itself having any effect on resistance. A5 is linked with either A3 or A4 with a crossover value of 10%.

The gene A1 from Baumforth A, which confers resistance to strains 1 and 3, when combined with A3 gives resistance to strain 2 also. Thus the three strains of A. rubi at present recognized on raspberries in Britain can be controlled by using either the combination A1A2 or A1A3.

Recently, a publication under this title has been distributed by Drs O. G. and M. J. Fahmy. On top of every page, it carries my name and not that of the authors. This has already resulted in its summary having been printed mistakenly as ‘author's summary’ of a paper of mine in Biological Abstracts. Since this curious publication is likely to lead to more confusion, its origin is explained below.