Sandy (sdy) is a mouse mutant with diluted pigmentation which recently arose in the DBA/2J strain. Genetic tests indicate it is caused by an autosomal recessive mutation on mouse Chromosome 13 near the cr and Xt genetic loci. This mutation is different genetically and hematologically from previously described mouse pigment mutations with storage pool deficiency (SPD). The sandy mutant has diluted pigmentation in both eyes and fur, is fully viable and has prolonged bleeding times. Platelet serotonin levels are extremely low although ATP dependent acidification activity of platelet organelles appears normal. Also, platelet dense granules are extremely reduced in number when analysed by electron microscopy of unfixed platelets. Platelets have abnormal uptake and flashing of the fluorescent dye mepacrine. Secretion of lysosomal enzymes from kidney and from thrombin-stimulated platelets is depressed 2- and 3-fold, and ceroid pigment is present in kidney. Sandy platelets have a reduced rate of aggregation induced by collagen. The sandy mutant has an unusually severe dense granule defect and thus may be an appropriate model for cases of human Hermansky-Pudlak syndrome with similarly extreme types of SPD. It represents the tenth example of a mouse mutant with simultaneous defects in melanosomes, lysosomes and/or platelet dense granules.

Genetic variance and fixation probabilities are evaluated for a model of a quantitative trait at a balance between mutation, selection and drift in which many alleles can segregate at each locus. If the distribution of effects of new mutant alleles is such that mutations are unconditionally deleterious, as might be the case in natural populations, genetic variance maintained is proportional to the number of mutations occurring in the genome per generation, but is independent of the number of loci at which they appear. If selectively advantageous alleles can occur these tend to interfere to a greater extent with each others' fixation and increasing mutation rate leads to a decrease in the genetic variance as a fraction of the variance maintained in the absence of selection. Fixation probabilities of new mutant alleles approach that for neutral alleles with increasing mutation rate at a locus irrespective of their effects on fitness. The additive genetic variance contributed by the locus may appear to be ‘decoupled’ from the fixation rate of mutant alleles.

Using mice that were mosaics for both Xce and phosphoglycerate kinase (Pgk-1) alleles, we present further evidence that the parental source of the X chromosome may affect the probability of that X chromosome remaining active. The reciprocal cross differences in PGK-1 activity described here are intermediate between those published previously for other alleles of Xce.

Lines of mice have been selected for 32 generations for either high or low fat content, resulting in a threefold divergence in the selection criterion (estimated fat content of males at 14 weeks of age). Male mice from both lines were dissected at a series of ages between 4 and 26 weeks and the following traits measured or estimated: body weight, fat content, lean weight, and the weights of several fatpads and internal organs. The lines appeared to have a similar underlying lean weight upon which the Fat line accumulated fat at a faster rate. This accumulation continued unabated in the Fat lines for at least 26 weeks but had effectively ceased by 8 weeks of age in the Lean. The liver and kidneys were slightly larger in the Fat line but there were no differences in the weights of heart, lung or spleen. This detailed phenotypic description of the lines complemented previous reports describing correlated changes in their physiology. The threefold divergence in estimated fat content was less than that in one of its component traits, growth of gonadal fatpad, but was greater than the divergence in other physiological indicators, i.e. the activity of lipogenic enzymes in vitro and direct measurement of lipogenic flux. Testis size in the Fat line was consistently lower than in the Lean although the Fat line was slightly more fecund, apparently due to a higher prenatal survival rate.

Effects of a recessive gene causing high growth (hg) were studied on two major components of the growth axis in mice. Plasma and pituitary levels of growth hormone and plasma levels of insulin-like growth factor I (IGF-I) were measured in three lines homozygous for hg, each compared with a control line of alike genetic background but wild type for the hg locus (Hg). Line Gh (hghg) and line GH (HgHg) are from a line which had undergone long-term selection for high postweaning weight gain; line Ch (hghg) and line CH (HgHg) were extracted from the second backcross of Gh to C57BL/6J; line L54 (hghg) was from the sixth backcross to C57BL/6J (B6) (HgHg). Pituitary GH levels and plasma IGF-I levels were measured in both sexes at 3, 4·5, 6 and 9 wk of age. Plasma growth hormone was measured in 8- to 12-wk-old males at hourly intervals from 08.00 to 17.00. Body weight in lines homozygous for hg at 6 and 9 wk of age was 10–30% greater than in control lines. The ontogeny of this increased growth depended on genetic background. Pituitary growth hormone content was 52% lower in the two hghg lines measured (lines Ch and Gh) than in control lines at 4·5, 6 and 9 wk. Plasma growth hormone levels were also much lower in hg mice, with values only 20–30% of those in their respective controls, hg lines showed consistently low plasma growth hormone levels throughout the 9 hr sampling period, while control lines expressed the characteristic pulsatile hormone secretion. In contrast, plasma IGF-I levels were greater in line Ch (hghg) than in line CH (HgHg) at 3, 4·5 and 9 wk, and were also greater in line Gh (hghg) vs. line GH (HgHg) at 6 wk of age. The results suggest that the growth enhancing effect of the hg gene occurs through an IGF-I-mediated process. In addition, the genetic background itself is also a factor in the phenotypic expression of the gene.

An experimental method is proposed for detecting the effects of positive natural selection on DNA polymorphisms. Since beneficial mutations are expected to increase in frequency faster than neutral mutations, variants which have reached high frequencies in a relatively short period could be linked to some beneficial mutation. D. melanogaster has a cosmopolitan polymorphic inversion -In(2L)t - whose age in some local populations has been estimated. Setting the age of In(2L)t as the upper limit for the age of variants, we searched for variants whose frequencies were possibly influenced by positive natural selection. We detected a single candidate whose frequency and distribution met the requirements imposed by our method.

The DNA repair hypothesis for the maintenance of sex states that recombination is necessary for the repair of double-strand DNA damage. In a closed (mitotic) genetic system crossing-over generates homozygosity. This reduces fitness if deleterious recessive alleles become expressed. Thus, outcrossing is required to restore heterozygosity destroyed by recombination. The repair hypothesis is tested by comparing outcrossing sexuality with a hypothetical parthenogenic strategy (the Prudent Reparator) which destroys as little heterozygosity during repair as possible. In the Prudent Reparator, repair of double-strand DNA damage results in a small amount of homozygosity due to gene conversion only, since this process does not render outside markers homozygous. Diploidy, deleterious recessives, multiplicative fitness and linkage equilibrium in mutation-selection balance are assumed. The average fitness of this population increases, and complementation (i.e. masking of recessives in heterozygous form) decreases with the rate of damage per locus. The equilibrium fitness of the Prudent Reparator can be well above that of the sexual population. A lower complementation ability of parthenogens may not be an impenetrable barrier to their successful establishment if the invader's genome is relatively uncontaminated by mutant alleles: there are always such genotypes in the sexual population. Thus, the Prudent Reparator could solve the problem of repairing damage as well as that of invading an existing outcrossing population. As we do not see this strategy widely adopted instead of sexuality, the repair hypothesis is likely to miss some essential feature of the evolution of sex.

This paper describes the relationship between probabilities of identity by descent and the distribution of coalescence times. By using the relationship between coalescence times and identity probabilities, it is possible to extend existing results for inbreeding coefficients in regular systems of mating to find the distribution of coalescence times and the mean coalescence times. It is also possible to express Sewall Wright's FST as the ratio of average coalescence times of different pairs of genes. That simplifies the analysis of models of subdivided populations because the average coalescence time can be found by computing separately the time it takes for two genes to enter a single subpopulation and time it takes for two genes in the same subpopulation to coalesce. The first time depends only on the migration matrix and the second time depends only on the total number of individuals in the population. This approach is used to find FST in the finite island model and in one- and two-dimensional stepping-stone models. It is also used to find the rate of approach of FST to its equilibrium value. These results are discussed in terms of different measures of genetic distance. It is proposed that, for the purposes of describing the amount of gene flow among local populations, the effective migration rate between pairs of local populations, M^, which is the migration rate that would be estimated for those two populations if they were actually in an island model, provides a simple and useful measure of genetic similarity that can be defined for either allozyme or DNA sequence data.