The t haplotypes are variant forms of the proximal one-third of chromosome 17 in the mouse. They contain four inversions (relative to the wildtype DNA) extending over most of this region and house a number of male sterility factors. Males carrying two complete t haplotypes (t/t) are sterile, as are males homozygous for S2, the sterility factor located in the most distal (relative to the centromere) inversion. Males homozygous for the sterility factor S1, located in the most proximal inversion, are not sterile; however, if such a male also is heterozygous for other sterility factors, then sterility results. It has been suggested therefore that homozygosity for S1 enhances the detrimental action of other sterility factors. Sperm from t/t males have severe motility defects and are unable to penetrate investment-free eggs, while sperm from fertile t/+ mice have less serious motility defects and exhibit a delay in penetration of investment-free eggs. To determine whether homozygosity for S1 enhances the cellular defects exhibited by sperm from mice heterozygous for other sterility factors, we compared the motility and egg-penetrating ability of sperm from fertile mice homozygous for S1 to that of sperm from mice carrying one complete t haplotype and one proximal or distal partial t haplotype. The data suggest that sperm from males carrying a proximal partial t haplotype and a complete t haplotype have serious defects in motility and penetration of the investment-free egg, and support the hypothesis that S1 enhances the detrimental effects of other sterility factors within the t haplotype.

Published reports suggest that the incidence of monozygotic twinning in women is increased after hormonally induced ovulation. Since some statistical evidence exists to indicate that monozygotic twinning may also occur in mice, we attempted to devise a mouse system in which the incidence of such twinning could be compared after spontaneous versus hormonally induced ovulation, in order to analyse the developmental basis of such an effect. We used phenotypic identity in litters segregating for ten genetic loci (not all independent) to indicate possible twin pairs. DNA fingerprinting using three human minisatellite probes was then performed blind on these pairs and on sibling controls. From a total of over 2000 mice born, 40 apparently identical pairs were identified, on which DNA finger-printing was successfully carried out on 35 pairs. All proved to be derived from different zygotes. We conclude that monozygotic twin pairs are either extremely rare in the stock of mice that we studied, or have such reduced viability that their chance of surviving to weaning is low.

Transpositive mutagenesis was employed to prepare genetic strains useful in cloning the Virescent-1 locus (V1) of maize. A stepwise approach was used based on: (1) the isolation of putative insertion phenotypes (62 cases); (2) the verification of the genetic nature of the selected events (36 v1-m mutant alleles induced); (3) the accurate genetic study of 11 alleles; (4) the genetic assessment that the alleles v1-m1 and v1-m4 are due to the insertion of a Ds element into the locus V1; (5) the proof that a Ds-like DNA element induces the inactivation of the wild type function in the allele v1-m1. The phenotype of the unstable alleles, studied by germinating and keeping maize seedlings at the temperature of 18 °C, are the following: alleles v1-m1, v1-m9, v1-m11, v1-m17 and v1-m18 showing a few revertant green sectors on their leaves; v1-m4 exhibiting a reverse type of variegation; alleles v1-m2 and v1-m13 with a coarse pattern of variegation; alleles v1-m12, v1-m21 and v1-m23 frequently showing leaves part green with white stripes and part white with green stripes. For the alleles studied, in addition to somatic instability, germinal reversions also occurred. In some cases, these reversions resulted in stable derivatives with a different colour from that of the wild-type (‘near green’ or pale phenotypes). The results presented not only allow the v1-m1 allele to be chosen as a starting material for cloning the V1 locus, but also define the molecular strategy to be followed.

The effects of partial inbreeding on effective population size and rates of fixation of mutant genes are investigated in selected populations. Truncation selection and an infinitesimal model of gene effects for the selected trait are assumed. Predictions of effective size under this model are given for partial selfing and partial full-sib mating and an extension to a more general model is outlined. The joint effect of selection and partial inbreeding causes a large reduction in the effective size relative to the case of random mating. This effect is especially remarkable for small amounts of selected genetic variation. For example, for initial heritability 0·1 and proportion selected 1/6, the ratio of effective size to population size is 0·10 in populations with about 90% selfing while it is 0·85 in random mating populations. The consequence is a reduction in the fixation probability of favourable genes and, therefore, a reduction in the final response to selection. Stochastic simulations are used to investigate the effects of partial inbreeding and selection on fixation and extinction rates of genes of large effect and of recessive lethals with effects on the selected trait. For genes of very large effect, the effective size is not a critical factor and it is expected that partial inbreeding will be efficient in increasing fixation rates of recessive mutants. Lethal recessives are eliminated more frequently and their equilibrium frequency is lower under partial inbreeding, but only when their effects on the heterozygote are not very large.

Divergent artificial selection for abdominal bristle number in Drosophila melanogaster has been carried out starting from a genetically homogeneous base population. Lines with two different systems of mating, random (P lines) or between full sibs whenever possible (about 50%), random otherwise (I lines) were compared. Responses after 40 generations of selection were mostly due to one or two mutations of large effect (0·2 to 2 phenotypic standard deviations) per line. Ten mutations affecting the selected trait were individually studied (five lethal and five non-lethal, these being predominantly additive). These mutations satisfactorily explain the response attained, although some minor mutations may also be involved. No evidence of epistasis for bristle number was found. The average final divergence was 57% larger in the P lines, but it was mostly due to lethals or highly deleterious mutations. Thus, after relaxation of selection, the ranking reversed and the mean divergence became significantly larger in the I lines (14%). Analysis of inbreeding showed that the very small amount of variation created by spontaneous mutations (a heritability for the selected trait of about 3%) was responsible for a reduction in the effective size of about 50% in the I lines (relative to the case with random selection), but only about 10% in the P lines. Mutational heritabilities estimated from the response to selection (0·05–0·18%) were within the range usually found for this trait in previous experiments. REML estimates account for correlations between relatives, and were much larger in those lines where the response was due to lethal mutations, as these do not contribute to response after reaching maximum frequency.

An analysis of mutation accumulation in finite, asexual populations shows that by modeling discrete individuals, a necessary condition for mutation–selection balance is often not met. It is found that over a wide parameter range (whenever N e−μ/s < 1, where N is the population size, μ is the genome-wide mutation rate, and s is the realized strength of selection), asexual populations will fail to achieve mutation–selection balance. This is specifically because the steady-state strength of selection on the best individuals is too weak to counter mutation pressure. The discrete nature of individuals means that if the equilibrium level of mutation and selection is such that less than one individual is expected in a class, then equilibration towards this level acts to remove the class. When applied to the classes with the fewest mutations, this drives mutation accumulation. This drive is in addition to the well-known identification of the stochastic loss of the best class as a mechanism for Muller's ratchet. Quantification of this process explains why the distribution of the number of mutations per individual can be markedly hypodispersed compared to the Poisson expectation. The actual distribution, when corrected for stochasticity between the best class and the mean, is akin to a shifted negative binomial. The parameterization of the distribution allows for an approximation for the rate of Muller's ratchet when N e−μ/s < 1. The analysis is extended to the case of variable selection coefficients where incoming mutations assume a distribution of deleterious effects. Under this condition, asexual populations accumulate mutations faster, yet may be able to survive longer, than previously estimated.

A method of using information on the location of markers to improve the efficiency of markerassisted selection (MAS) in a population produced by a cross between two inbred lines is developed. The method is closer to mapping QTL than the selection index approaches to MAS described by previous authors. We use computer simulations to compare our method with phenotypic selection and two selection index approaches, simulations being performed on three genetic maps. The simulations show that whilst MAS can be considerably more efficient than phenotypic selection differences between the three MAS methods are slight. Which of the MAS methods is best depends on a number of factors: in particular the genetic map, the time scale under consideration and the population size are of importance.

The amount and pattern of genetic variation in a population can be estimated from genes or DNA sequences sampled from the population. Although random sampling is assumed in almost all cases, we often do not know whether sampling is random or not. Using a simple non-random sampling model, the effects of non-random sampling on the estimation of parameters in population genetics were investigated. This non-random sampling model assumes that n genes are randomly sampled with replacement from m genes which were randomly sampled from a large random mating population, and various degrees of non-randomness can be generated by changing the value of m. The results obtained show that the effect of non-random sampling on the number of alleles and the number of segregating sites is substantially large whereas the effect of non-random sampling on heterozygosity and the average number of nucleotide differences is negligibly small unless non-randomness is extremely large. The effects of non-random sampling on the tests of neutrality were also investigated, and the results obtained indicate that the effect of non-random sampling is stronger on Fu and Li's tests than on Tajima's test.