Competitions between matched pairs of diploid strains of Saccharomyces cerevisiae, one capable of undergoing sexual recombination (MAT-heterozygous) and the other not (MAT-homozygous), have proved useful for measuring the effects of mitotic and meiotic recombination and DNA repair on competitive ability in this organism. Overall competitive differences between the strains can be enhanced by converting them to petites (aerobic respiration incompetent). Here we report the results of competitions between pairs of strains that also differ in their ability to undergo mismatch repair. In petite strains, the growth rates of mismatch-repair defective strains declined over time regardless of their MAT genotype. Mismatch-repair proficient MAT-heterozygous strains did not show a decline, while repair-deficient MAT-homozygous strains did. The decline appears to be due to the accumulation of deleterious mutations of small effect, which can be corrected by MAT-heterozygous strains having intact mismatch repair. The relative competitive abilities of MAT-heterozygous and MAT-homozygous strains diverged during the course of the competitions, and the variance of this divergence increased significantly when mismatch repair was defective. This large stochastic component indicates that a relatively small number of deleterious mutations may be involved. The accumulation of deleterious mutations and their subsequent repair may have a bearing on the origin of sex in this organism.

To clone the Bombyx xanthine dehydrogenase (XDH) gene as a dominant marker for silkworm transgenesis, we performed nested reverse transcriptase–polymerase chain reaction (RT-PCR) using embryonic mRNA and primers designed from the conserved region of Drosophila and rat XDH genes. Sequencing of amplified 180 bp fragments showed that two different sequences were present in the fragments. Since both possessed striking similarity to XDH genes of other organisms, we considered these to be portions of silkworm XDH genes and designated them BmXDH1 and BmXDH2. Subsequently we cloned separately the entire region of the two cDNAs by PCR using phage DNA of an embryonic cDNA library and sequenced them. The two cDNAs were around 4 kb in size and possessed complete open reading frames. The deduced amino acid sequences of the two BmXDHs were very similar to each other and to those of other organisms. The expression pattern of wild-type larvae basically followed the tissue specificity of the enzyme and no significant difference was observed between the two XDH genes. The expression of both genes was detected in the XDH-deficient mutants, oq and og, but non-synonymous substitutions were specifically detected in the BmXDH1 of the oq mutant. In addition, a length polymorphism of the second intron of the BmXDH1 co-segregated with the oq translucent phenotype, suggesting that deficiency in BmXDH1 is the cause of the oq translucent phenotype.

We have discovered, in an inbred line (Loua) of Drosophila melanogaster from Zaïre, a third chromosome showing unusual P element repression. Repression of P element transposition by this chromosome, named Loua3, is dominant zygotic and has three unusual properties. Firstly, its repression of the gonadal dysgenesis caused by a strong P haplotype is strongly temperature-dependent, being most evident at higher rearing temperatures. Secondly, subdivision of Loua3 by recombination abolishes repression: the effect is apparently a function of the intact chromosome. Finally, Loua3 also diminishes somatic lethality when chromosomes carrying many ‘ammunition’ elements (Birmingham2) are exposed to the constitutive transposase source Δ2-3(99B). The chromosome has 17 P elements, none full-length, located in at least 12 dispersed positions.

Natural populations of Drosophila kikkawai were collected in India and Sri Lanka, along a latitudinal transect ranging from 6·8° to 31·8° N latitude. Six morphometrical traits were analysed: wing and thorax length, body weight, ovariole number, and abdominal and sternopleural bristle numbers. Significant clines were observed for the three size-related traits and for ovariole number, corresponding to a regular increase in the mean value with latitude, but not for bristle numbers. Due to the utilization of two types of laboratory food, data were distributed into two separate data sets. A low-nutrient food produced smaller flies on average because of more intense crowding. The two rearing conditions produced significant clines but with significantly different slopes. The wing/thorax ratio, which is inversely related to wing loading, also increased with latitude. The analysis of Indian climatic conditions suggested that winter temperature, decreasing from south to north, could be more efficient than summer temperature, which varies in an opposite way, as a selective factor for inducing the clinal variations. The sibling species D. leontia, which is known only from the humid tropics, was found to be much smaller than D. kikkawai and did not fit the clinal regressions. Such morphological differences should help to identify the two species when found in sympatry.

Information on the nature of epistasis between alleles affecting fitness is hardly available, but relevant for, among other issues, our understanding of the evolution of sex and recombination. Evidence of synergistic epistasis between deleterious mutations is support for the Mutational Deterministic hypothesis of the evolution of sex, while finding antagonistic epistasis between beneficial alleles would support the Environmental Deterministic hypotheses. Both types of epistasis are expected to cause negatively skewed fitness distributions of full-sib offspring from a sexual cross. Here, we have studied the form of the distribution of a variety of quantitative characters related to fitness by searching the literature. The fitness traits encountered include the mycelial growth rate in fungi, and earliness, resistance against pathogens, seed number, and pollen fitness in plants. Fitness-related traits in plants show almost exclusively negative skewness, while the results for fungal species are more ambiguous. Possible sources of negative skewness other than epistasis, such as recessiveness of deleterious alleles or a negatively skewed error variance, were tested and found to be unimportant. We argue that these results suggest the existence of synergistic epistasis between deleterious alleles or antagonistic epistasis between beneficial alleles in plants, which is general support for the currently popular hypotheses of sex and recombination, but does not distinguish between them.

A simple regression strategy for mapping multiple linked quantitative trait loci (QTLs) in inbred populations is proposed and applied to data from a non-obese diabetic (NOD) mouse backcross. The method involves adding and deleting markers from a linear model in a stepwise manner, allowing the association with a particular marker to be examined once associations with other (in particular neighbouring) markers have been taken into account. This approach has the advantage of using programs available in standard statistical packages while still allowing adequate separation of possible multiple linked effects. For the mouse backcross, using these methods, at least two and possibly three diabetogenic loci are detected on each of chromosomes 1 and 3. Some evidence for epistasis is seen between the loci on chromosome 1, with a possible additional epistatic interaction between the loci on chromosome 3. Congenic strain analysis of the chromosome regions in NOD diabetes suggests that although the true type I error rate may be larger than that suggested by the nominal P values, our results nevertheless correspond well with those disease loci and interactions detected using a congenic approach, indicating that the regression method may be a powerful strategy for the detection and characterization of QTLs in inbred populations.

In this research we estimated the contribution of a major-gene effect to the control of litter size in hybrids between two local populations of the house musk shrew (Suncus murinus). Segregation analysis was performed on the basis of a mixed polygene and major-gene model. The model presumes that two parental populations may differ from each other in gene frequencies and in the values of polygenic effects but not in the major-gene contribution of the trait. Moreover, the peculiarity of the trait – litter size – is taken into account. This trait is not an individual attribute. It characterizes the parental couple and may depend on the genotypes of both parents. Results of segregation analysis of a large hybrid pedigree of Suncus murinus indicate that the parental populations differ in the allele frequency of the major gene (one population is homozygous, while the other contains the two alleles in approximately equal proportions) and in the values of average polygenic effects. Both major-gene and polygenic components are necessary for the correct description of litter size inheritance in interracial hybrids of S. murinus, inasmuch as the exclusion of either of them leads to a significant drop in likelihood. The Elston–Stewart criterion also confirms the Mendelian inheritance of the major gene.

We present a multipoint algorithm to map quantitative trait loci (QTLs) using families from outbred populations with a variable number of sibs. The algorithm uses information from all markers on a chromosome simultaneously to extract information of QTL segregation. A previous multipoint method (Kruglyak & Lander (1995) American Journal of Human Genetics57, 439–454) extracts information using a hidden Markov model. However, this method is restricted to small families (<10 sibs). We present an approximate hidden Markov model approach that can handle large sibships while retaining similar efficiency to the previous method. Computer simulations support the notion that data sampled from a small number of large families provide more power than data obtained from a large number of small families, under the constraint that the total number of individuals for the two schemes is the same. This is further reflected in simulations with variable family sizes, where variance in family size improves the statistical power of QTL detection relative to a constant size control.

The magnitude of inbreeding depression in Drosophila melanogaster appears too large to be accounted for by mutational load with multiplicative fitness interactions among loci, if current estimates of mutation and selection parameters are valid. One possible explanation for this discrepancy is synergistic epistasis among the fitness effects of deleterious mutations. A simple model of the effect of synergistic epistasis on the inbreeding load is developed. This model is used to show that deleterious mutations could account for the Drosophila data on the effects of inbreeding on components of fitness such as viability.