Seven imprinted genes are currently known in the mouse but none have been identified yet in the distal imprinting region of mouse Chromosome (Chr) 2, a region which shows striking linkage conservation with human chromosome 20q13. Both maternal duplication/paternal deficiency and its reciprocal for distal Chr 2 lead to mice with abnormal body shapes and behavioural abnormalities. We have tested a number of candidate genes, that are either likely or known to lie within the distal imprinting region, for monoallelic expression. These included 3 genes (Cebpb, E2f1 and Tcf4) that express transcription factors, 2 genes (Cyp24 and Pck1) that are involved in growth, 5 genes (Acra4, Edn3, Kcnb1, Mc3r and Ntsr) where a defect could lead to neurological and probably behavioural problems, and 3 genes (Cd40, Plcg1 and Rcad) that are less obvious candidates but sequence information was available for designing primers to test their expression. On/off expression of each gene was tested by reverse transcription–polymerase chain reaction (RT–PCR) analysis of RNA extracted from tissues of mice with maternal duplication/paternal deficiency and its reciprocal for the distal region of Chr 2. None of the 13 genes is monoallelically expressed in the appropriate tissues before and shortly after birth which suggests that these genes are not imprinted later in development. This study has narrowed down the search for imprinted genes, and valuable information on which genes have been tested for on/off expression is provided. Since there is considerable evidence of conservation of imprinting between mouse and human, we would predict that the 13 genes are not imprinted in human. Five of the genes: E2f1, Tcf4, Kcnb1, Cd40 and Rcad, have not yet been mapped in human. However, because of the striking linkage conservation observed between mouse Chr 2 and human chromosome 20, we would expect these genes to map on human chromosome 20q13.

Restriction enzyme molecular variation in Drosophila melanogaster Adh was compared between three natural populations from Europe, West Africa and East Africa. The frequency distribution of silent variation in the slow allele was compatible with the neutral model in all three samples. The number of haplotypes in East Africa was significantly higher than in the other two populations. The largest divergence, as measured by Fst, was between the East African population and a group made up from the West African, the European, and previously studied American populations. We suggest that a split first occurred within African populations at least 44000 years ago. European populations separated from West Africa more recently, between the last glacial maximum and the post-glacial optimum, 18000 to 8000 years ago. We suggest that this species was domesticated recently relative to human evolution, possibly with the advent of agriculture. Population differentiation with respect to the two allozymes, fast and slow, does not follow the geographical pattern of silent variation. It opposes European to both African populations, and probably results from selection for adaptation to alcohol in recent temperate populations.

We have determined the map position of the gene encoding a common precursor protein for diapause hormone and pheromone biosynthesis-activating neuropeptide (the DH-PBAN gene, Dh)in the silkmoth, Bombyx mori. First we compared the structure of introns in the DH-PBAN gene by the polymerase chain reaction, and found that the Dh locus carried three alleles, DhA1, DhA2 and DhB. The DhA1 and DhA2 alleles contained a fourth intron consisting of 740 bp, whereas DhB had a longer fourth intron of 770 bp. DhA1 and DhA2 contained a fifth intron consisting of 940 bp, whereas the fifth intron in DhB was much longer and consisted of 1700 bp. DhA1 was distinguished from DhA2 by an RFLP in the fifth intron after digestion with Rsa I. Linkage analyses using these polymorphisms showed that Dh was linked to the bp gene on chromosome 11, and independent of markers on chromosomes 1, 2, 3, 4, 5, 6, 7 and 13. To determine the map position, we obtained F1 hybrids between the n501 strain (K DhA1) and the w30 strain ( + KDhB), and backcrossed the F1 hybrid to females of the w30 strain. From the segregation of K and Dh in 864 individuals in the next generation, the recombination value was calculated as 25·5 % between K and Dh. Similarly we obtained backcross progeny between the No. 744 strain (BuDhA1) and the w30 strain ( + BuDhB), and calculated the recombination value between Bu and Dh as 30·4% from 487 progeny. Because k and Bu had already been mapped at positions 11–23·2 cM and 11–28·7 cM, respectively, we mapped Dh at 11--2·2 cM. The Dh locus is different from any loci which are known to control diapause, development or growth.

This paper studies the influence of two opposite forces, unidirectional unconditionally deleterious mutations and directional selection against them, on an amphimictic population. Mutant alleles are assumed to be equally deleterious and rare, so that homozygous mutations can be ignored. Thus, a genotype is completely described by its value with respect to a quantitative trait x, the number of mutations it carries, while a population is described by its distribution p(x) with mean M[p] and variance V[p] = σ2[p]. When mutations are only slightly deleterious, so that M » 1, before selection p(x) is close to Gaussian with any mode of selection. I assume that selection is soft in the sense that the fitness of a genotype depends on the difference between its value of x and M, in units of σ. This leads to a simple system of equations connecting the values of M and V in successive generations. This system has a unique and stable equilibrium, where U is the genomic deleterious mutation rate, δ is the selection differential for x in units of σ, and p is the ratio of variances of p(x) after and before selection. Both δ and ρ are parameters of the mode of soft selection, and do not depend on M or V. In an equilibrium population, the selection coefficient against a mutant allele is ŝ = δ2[U(2–ρ)]−1. The mutation load can be tolerable only if the genome degradation rate υ = U/σ is below 2. Other features of mutation-selection equilibrium are also discussed.

A general representation of multilocus selection is extended to allow recombination to depend on genotype. The equations simplify if modifier alleles have small effects on recombination. The evolution of such modifiers only depends on how they alter recombination between the selected loci, and does not involve dominance in modifier effects. The net selection on modifiers can be found explicitly if epistasis is weak relative to recombination. This analysis shows that recombination can be favoured in two ways: because it impedes the response to epistasis which fluctuates in sign, or because it facilitates the response to directional selection. The first mechanism is implausible, because epistasis must change sign over periods of a few generations: faster or slower fluctuations favour reduced recombination. The second mechanism requires weak negative epistasis between favourable alleles, which may either be increasing, or held in check by mutation. The selection (si) on recombination modifiers depends on the reduction in additive variance of log (fitness) due to linkage disequilibria (υ1 < 0), and on non-additive variance in log (fitness) (V′2, V′3,.. epistasis between 2, 3.. loci). For unlinked loci and pairwise epistasis, si = − (υ1 + 4V2/3)δr, where δr is the average increase in recombination caused by the modifier. The approximations are checked against exact calculations for three loci, and against Charlesworth's analyses of mutation/selection balance (1990), and directional selection (1993). The analysis demonstrates a general relation between selection on recombination and observable components of fitness variation, which is open to experimental test.

The variation from spontaneous mutations for 6-week body weight in the mouse was estimated by selection from a cross of two inbred sublines, C57BL/6 and C57BL/10, separated about 50 years previously from the same inbred line. Selection was practised high and low for 12 generations from the F2, followed by one generation of relaxation. The lines diverged by approximately 1·7 g or 0·7 sd. The additive genetic variance was estimated in the F2 by restricted maximum likelihood and from the selection response, and from this variance the mutational heritability hM2 was estimated using the number of generations since divergence. Estimates of hM2 range from 0·08 to 0·10% depending on the method of analysis. These estimates are similar to those found for other species, but lower than other estimates for the mouse. It is concluded that substantial natural and, perhaps, artificial selection operated during the maintenance of the sublines.

We have developed molecular markers that distinguish between several inbred and congenic mouse strains using polymerase chain reaction (PCR) amplification of genomic DNA repeat sequences. Mouse genomic DNA, digested with four base recognition site-restriction endonucleases, was amplified by PCR using primers for the following repeat sequences: Bl (Alu homolog), LINE, LLR3, IAP, human Alu and myoglobin. Amplification products analysed by agarose gel electrophoresis and stained with ethidium bromide produced unique DNA fragments, some of which are specific for each of 12 strains tested. This method can be used for molecular analysis of the mouse genome, including genetic monitoring.