Mouse t haplotypes have been divided into nine subregions that are each defined by one or more molecular markers. In previous studies, three of these subregions were shown to contain ‘distorter loci’ that interact to effect the transmission-ratio distortion phenotype characteristic of all complete t haplotypes. To determine which of the remaining six subregions also play a role in this phenotype, we analysed the accumulated data on transmission ratio distortion from males that carried one of 26 different combinations of two partial t haplotypes. We have obtained evidence for the association of two additional subregions with distorter loci. First, we present further evidence for the existence of a previously postulated distorter locus, Tcd-3, and describe its mapping to the T66C subregion. Secondly, we describe the identification of a new distorter locus, Tcd-4, in association with the subregion defined by the structural gene for the TCP-1 protein. Further studies indicate that two doses of the Tcd-4 locus are equivalent in effect to a single dose each of Tcd-4 and a second distorter locus, Tcd-1. This result suggests that different distorter locus products could have a common mode of action.

Male mice heterozygous for two distorter genes, Tcd-1 and Tcd-2, of the mouse t-complex but homozygous wild type for the responder, were generated by crossing animals carrying the partial t-haplotypes th51 and th18 to inbred strains. The fertility of these males was then compared with that of their brothers carrying normal chromosome 17s. On three of the inbred backgrounds used, C3H/HeH, C57BL/6J and TFH/H, the th51th18 + / + + + males were significantly less fertile than their normal sibs. With the fourth inbred strain used, SM/JH, both types of male were nonnally fertile. This confirmed earlier preliminary findings that when both homologues of chromosome 17 carry wild-type alleles of the responder, heterozygosity for the distorter genes is sufficient to impair fertility, but the effect varies with genetic background. These results are consistent with the concept that both the transmission ratio distortion and the male sterility caused by the t-complex are due to harmful effects of the distorter genes on wild-type alleles of the responder.

NMRI/Han mice ovulate significant numbers of diploid oocytes after gonadotrophin stimulation, most of them arrested at metaphase I. In contrast, females from other mouse strains ovulate only oocytes having completed meiosis I. We investigated the heritability of the trait Dipl I by analysing F1 hybrid females from crosses between the sensitive NMRI/Han stock and two mouse strains (C3H/HeHan and BALB/c) considered as non-sensitive, and females from backcrosses to NMRI/Han males (only crosses with C3H/HeHan). The results show (1) that the trait Dipl I is inheritable; (2) that an X-chromosomal (location proximally from the X–Y pairing region) or autosomal recessive mode of inheritance is excluded; and (3) that the expression of the trait, measured as frequency of diploidy, is modulated by a maternally transmitted factor.

The maintenance of polygenic variability by a balance between mutation and stabilizing selection has been analysed using two approximations: the ‘Gaussian’ and the ‘house of cards’. These lead to qualitatively different relationships between the equilibrium genetic variance and the parameters describing selection and mutation. Here we generalize these approximations to describe the dynamics of genetic means and variances under arbitrary patterns of selection and mutation. We incorporate genetic drift into the same mathematical framework.

The effects of frequency-independent selection and genetic drift can be determined from the gradient of log mean fitness and a covariance matrix that depends on genotype frequencies. These equations describe an ‘adaptive landscape’, with a natural metric of genetic distance set by the covariance matrix. From this representation we can change coordinates to derive equations describing the dynamics of an additive polygenic character in terms of the moments (means, variances, …) of allelic effects at individual loci. Only under certain simplifying conditions, such as those derived from the Gaussian and house-of-cards approximations, do these general recursions lead to tractable equations for the first few phenotypic moments. The alternative approximations differ in the constraints they impose on the distributions of allelic effects at individual loci. The Gaussian-based prediction that evolution of the phenotypic mean does not change the genetic variance is shown to be a consequence of the assumption that the allelic distributions are never skewed. We present both analytical and numerical results delimiting the parameter values consistent with our approximations.

The level of histidine decarboxylase in mouse kidney normally differs between the sexes with females higher than males. In a strain derived from feral Danish mice (DAN), however, both males and females have the same, high, HDC activity due to the males being insensitive to repression by testosterone. Genetic analysis indicates that this insensitivity is caused by a variant allele of a new gene in the histidine decarboxylase gene complex, Hdc-a; the Hdc-ab allele in C57BL/10 confers high sensitivity to testosterone whereas the Hdc-aw allele in the DAN strain confers low sensitivity. In addition, the DAN strain has a novel haplotype for the other three known elements of [Hdc]: the allele Hdc-sd of the structural gene, the Hdc-cd allele of the gene determining enzyme concentration, and the oestrogen-inducible allele Hdc-eb.

Under a two-locus model with additive genes which combine multiplicatively to determine a quantitative trait, heterosis is generally observed in the F1 It is positive only if both frequencies of the best allele at each locus are not higher in the same parental population. In the F2, heterosis depends on the rate of recombination between the two loci. If linkage is tight, F1 superiority is nearly halved in the F2. But if the two genes are independent, heterosis is maintained in the F2 at the same level as in the F1.

The average effect and average excess both measure the phenotypic effects of gametes in a population. A matrix notation is introduced that provides a general analytical solution for the average effects at a single locus with k alleles that can be solved for any population regardless of its genotype frequencies. This same notation also provides an easy way of deriving and generalizing to k alleles the well-known relationships between average effects and average excesses that exist under random-mating and regular deviations from Hardy–Weinberg equilibrium due to inbreeding.

The widespread use of restriction endonucleases and DNA sequencing provides a wealth of data on the genetic structure of natural populations. From such data, detailed phylogenies can be constructed and qualitatively different kinds of mutational and substitutional processes can be studied. A neutral model can be constructed to describe the frequencies of sequence haplotypes according to the haplotypes from which they arose and the types of substitution that distinguish them. One feature of such a model is that it examines the ancestors of various sequences. Deleterious selection against a character has a distinct effect on descendant sequences. Individuals containing many deleterious characters leave few or no descendants because these individuals are quickly eliminated by selection. Hence, such a model lends itself to the study of deleterious selection. It is possible to determine if selection is required by searching for any set of mutation rates that can explain an observed set of data. Simulations of artificial populations without selection suggest that this method seldom indicates selection when none is present. Furthermore, recent recombination events between the sequences do not induce false indications of deleterious selection. The method may, however, require relatively large simple sizes in order to accurately reflect the true nature of populations. The method is often very conservative and may not indicate selection when it is, in fact, present.