Homozygous or hemizygous expression of an X-linked wing mutant of Drosophila robusta varies from a rudimentary wing that does not reach the tip of the abdomen (called ‘club’) to forms with full-sized but curled or crumpled wings (called ‘curly’). Homozygous club females crossed to flies from natural populations or laboratory stocks derived from wild flies invariably produce significantly less club male progeny than the 100% expected, most of them exhibiting less severe phenotypes: ‘curly’ forms and wild-type. The male progeny from similar crosses using curly females tend to be predominantly normal. By contrast, the male progeny of outcrossed females homozygous for an X-linked eye colour mutant, vermilion, are all vermilion. The data indicate that natural populations of D. robusta contain suppressors of the wing mutant but not of the eye colour mutant studied. Activity of the suppressors differs by gender: in experiments in which genetic theory expects similar results in the two sexes, males consistently show stronger effects of the suppressors than females.

We have used the method of disequilibrium pattern analysis to examine associations between the threonine-glycine (Thr-Gly) encoding repeat region of the clock gene period (per) of Drosophila melanogaster, and polymorphic sites both upstream and downstream of the repeat, in a number of European fly populations. The results are consistent with the view that selection may be operating on various haplotypes which share the Thr-Gly length alleles encoding 17, 20 and 23 dipeptide pairs, and that the repeat itself may be the focus for selection. These conclusions lend support to a number of other population and behavioural investigations which have provided evidence that selection is acting on the Thr-Gly region. The linkage analysis was also used to infer an approximate mutation rate (μ) for the repeat, of 10−5<μ<4×10−5 per gamete per generation. Direct measurements of the mutation rate using the polymerase chain reaction in a pedigree analysis of tens of thousands of individuals do not contradict this value. Consequently, the Thr-Gly repeat does not have a mutation rate that is as high as some of the non-coding minisatellites, but it is several orders of magnitude higher than the nucleotide substitution rate. The implications of this elevated mutation rate for linkage disequilibria and selection are discussed.

In vitro studies using highly purified calf thymus RNA polymerase II and a fragment spanning the first intron of H3.3 as template DNA have demonstrated the existence of a strong transcription termination site consisting of thymidine stretches. In this study, nuclear run-on experiments have been performed to assess the extent to which transcription elongation is blocked in vivo using DNA probes corresponding to regions 5′ and 3′ of the in vitro termination sites. These studies suggest that H3.3 expression is stimulated following the inhibition of DNA synthesis through the elimination of the transcription elongation block. Interestingly, both the in vivo and in vitro experiments have revealed that the transcriptional block/termination sites are positioned immediately downstream of a 73 bp region that has been over 90% conserved between the chicken and human H3.3 genes. The extreme conservation of this intronic region suggests a possible role in maintaining cis-acting function. Electrophoretic mobility shift experiments show that HeLa cell nuclear extracts contain protein factors that bind specifically to the region of transcription elongation block. Furthermore, we demonstrate a correlation between the protein binding activity and the transcriptional block in cells that have been either arrested at the initiation of S phase or were replication-interrupted by hydroxyurea. DNA footprinting experiments indicate that the region of protein binding is at the 3′ end of the conserved region and overlaps with one of the three in-vitro-mapped termination sites.

The theory developed by Takahata and colleagues for estimating the effective population size of ancestral species using homologous sequences from closely related extant species was extended to take account of variation of evolutionary rates among loci. Nuclear sequence data related to the evolution of modern humans were reanalysed and computer simulations were performed to examine the effect of rate variation on estimation of ancestral population sizes. It is found that the among-locus rate variation does not have a significant effect on estimation of the current population size when sequences from multiple loci are sampled from the same species, but does have a significant effect on estimation of the ancestral population size using sequences from different species. The effects of ancestral population size, species divergence time and among-locus rate variation are found to be highly correlated, and to achieve reliable estimates of the ancestral population size, effects of the other two factors should be estimated independently.

Since the last glacial period forest trees have expanded to their present range very rapidly, with rates up to 500 m yr−1 for oaks in Europe, which can be explained only by the dispersion of acorns over long distances. We used a stratified dispersal model, including both diffusive and long-distance dispersal of seeds, to simulate the colonization of a 100 km×300 km grid by populations of oak trees. An appropriate rate of spread is obtained with rare dispersal at distances of the order of tens of kilometres. We simulated the effect of stratified versus diffusive dispersal of seeds on the spatial genetic structure at a maternally inherited locus. Founding events associated with stratified dispersal generate a high amount of genetic differentiation among populations, which is likely to persist for a long time after colonization. Using autocorrelation methods, we show that diffusive and stratified dispersals create quite different spatial patterns of variation for the maternally inherited locus. Stratified dispersal creates patchy patterns that are concordant with a previous experimental investigation of chloroplast DNA variation at a regional scale in the oaks Quercus petraea and Quercus robur. For plant populations that have passed through recent episodes of range expansion, long-distance dispersal events are probably the most important factors of spatial genetic structuring of maternally inherited genes at small or medium geographic scales.

Based on a deterministic mutation–selection model the concept of error thresholds is critically examined. It has often been argued that genetic information – for instance, an advantageous allele – can be selectively maintained in a population only if the mutation rate is below a certain limit, the error threshold, which is inversely related to the genome size. Here, I will show that such an inverse relationship strongly depends on the fitness model. To produce the error threshold, as given by Eigen (1971), requires that the fitness model is an extreme form of diminishing epistasis. The error threshold, in a strict sense, vanishes as epistasis changes from diminishing to synergistic. In the latter case even the usual definition of error thresholds becomes ambiguous. Initially, a finite sites model has been used to describe error thresholds. However, they can also be defined within the framework of the infinite sites model. I study both models in parallel and compare their properties as far as error thresholds are concerned. It is concluded that error thresholds possibly play a much less important role in molecular evolution than has often been assumed in the past.

In crosses between inbred lines linear regression can be used to estimate marker effects; these marker effects then allow marker-assisted selection (MAS) for quantitative traits. Weighting of marker and phenotypic information in MAS requires estimation of genetic variance associated with the markers: the usual estimators are biased, resulting in too much weight being placed on marker information relative to phenotypic information. In this paper we develop a cross-validation method to remove this bias, and show by simulation that response to selection using this method is almost as high as that achieved using optimal weighting of marker and phenotypic information.

A method for finding optimum breeding schemes which maximize genetic gain under index selection with constraints on the rate of inbreeding is derived. The selection index includes information on the candidate and its sibs. Optimization is for the numbers of males and females to be selected and for the index weights when fixed numbers of offspring per generation, heritabilities and time horizons are considered. The expected rate of gain after a number of generations of selection is combined with the expected asymptotic rate of inbreeding (ΔF) in a single objective function which is maximized for finding the optimum solutions. Under restricted inbreeding, optimum designs are very similar for maximizing gains at different time horizons. The optimum number of selected males (for giving maximum gains) increases with the size of the scheme and with the severity in restricting ΔF and decreases with the heritability. Low heritability, less severe restrictions on ΔF and large schemes lead to increases in the relative weights given to performance of relatives in the index. The presence of common environmental effects leads to increases in optimum mating ratio when the heritability is low, to increases in the number of selected males and to more intense selection within families. Gains from index selection are compared with gains from mass selection. Under restricted inbreeding the advantage of optimized index selection over mass selection is only notable when the heritability is low and the scheme is large (in which case indices put more emphasis on family information than mass selection) and when the heritability is high and the scheme is small (in which case indices put less emphasis on family information).