Selection and recombination in Drosophila melanogaster

Summary Artificial selection for wing length in Drosophila melanogaster resulted in changed crossing-over frequencies between three marker genes on the 2nd chromosome, b, cn and vg.The results suggest that artificial selection is a causal agent in producing the observed changes; moreover it is suggested that the modifications in cross-over frequency are controlled by extra-nuclear factors.Research supported by C.N.R. Consiglio Nazionale delle Ricerche Roma, Grant n. 115.2298.4791.     

Linkage disequilibrium in laboratory populations of Drosophila nasuta

Summary Natural populations of Drosophila nasuta are polymorphic for many gene arrangements. Two non-overlapping inversions of the third chromosome, III-2 and III-35, are most common and display extreme linkage disequilibrium. Six randomly mating laboratory stocks, each founded by one gravid female heterozygous in coupling for both III-2 and III-35, were observed after 32 generations. Significant linkage disequilibrium was observed in all stocks. Recombinants were found in only two stocks. The absence of effective recombination in some stocks and its presence in others might be due to different genotypic backgrounds. We suggest that natural selection, influencing recombination rates in several ways, and intrachromosomal epistasis between the two inversions were the main factors for the maintenance of linkage disequilibrium in D. nasuta.     

Linkage disequilibrium and inference of ancestral recombination in 538 single-nucleotide polymorphism clusters across the human genome

The prospect of using linkage disequilibrium (LD) for fine-scale mapping in humans has attracted considerable attention, and, during the validation of a set of single-nucleotide polymorphisms (SNPs) for linkage analysis, a set of data for 4,833 SNPs in 538 clusters was produced that provides a rich picture of local attributes of LD across the genome. LD estimates may be biased depending on the means by which SNPs are first identified, and a particular problem of ascertainment bias arises when SNPs identified in small heterogeneous panels are subsequently typed in larger population samples. Understanding and correcting ascertainment bias is essential for a useful quantitative assessment of the landscape of LD across the human genome. Heterogeneity in the population recombination rate, rho=4Nr, along the genome reflects how variable the density of markers will have to be for optimal coverage. We find that ascertainment-corrected rho varies along the genome by more than two orders of magnitude, implying great differences in the recombinational history of different portions of our genome. The distribution of rho is unimodal, and we show that this is compatible with a wide range of mixtures of hotspots in a background of variable recombination rate. Although rho is significantly correlated across the three population samples, some regions of the genome exhibit population-specific spikes or troughs in rho that are too large to be explained by sampling. This result is consistent with differences in the genealogical depth of local genomic regions, a finding that has direct bearing on the design and utility of LD mapping and on the National Institutes of Health HapMap project.     

Linkage and segregation distortion in Drosophila melanogaster

Segregation distortion is caused by a group of genetic elements in and near the centric heterochromatin of chromosome 2 of Drosophila melanogaster. These elements promote their preferential recovery in heterozygous males by rendering sperm bearing the homologous chromosome dysfunctional. Previous work has shown that numerous Y-autosome translocations are associated with the suppression of the segregation distorter phenotype. The present study examined the effects of translocations between the major autosomes upon the expression of segregation distortion. Autosomal translocations involving either the segregation distorter chromosome or its sensitive homologue had no significant effect upon the expression of segregation distortion. These results argue that linkage arrangement per se may not have a major effect on segregation distortion. The suppression of SD by specific Y-autosomal translocations may be due to the disruption of elements on the Y chromosome that are important for the expression of SD.     

Linkage disequilibrium, selection and recombination at three Loci

Limits to the relationship among linkage disequilibrium, selection and recombination at equilibrium in three-locus, two-allele, deterministic, discrete generation models are determined using linear programming techniques. These results show that the commonly used measures of linkage disequilibrium are not appropriate for a multilocus setting. Additionally, interactions among three loci are important in reducing the strength of selection necessary to maintain a given level of disequilibrium, relative to a two-locus model.     

A comparison of linkage disequilibrium patterns and estimated population recombination rates across multiple populations

Large-scale studies of linkage disequilibrium (LD) have shown considerable variation in the extent and distribution of pairwise LD within and between populations. Taken at face value, these results suggest that genomewide LD maps for one population may not be generalizable to other populations. However, at least part of this diversity is due to some undesirable features of pairwise LD measures, which are well documented for the D' and r2 measures. In this report, we compare patterns of LD derived from pairwise measures with statistical estimates of population recombination rates ( rho ) along a 10-Mb stretch of chromosome 20 in four population samples, comprising East Asians, African Americans, and U.K. and U.S. individuals of western European descent. The results reveal the expected variability of D' within and between populations but show better concordance in estimates of r2 for the same markers across the population samples. Estimates of rho correlate well across populations, but there is still evidence of population-specific spikes and troughs in rho values. We conclude that it is unlikely that a single haplotype map will provide a definitive guide for association studies of many populations; rather, multiple maps will need to be constructed to provide the best-possible guides for gene mapping.     

Time of recombination in the Drosophila melanogaster Oocyte

A test has been carried out to determine if the restrictive temperature (31°) acts to reduce recombination in the temperature-sensitive recombination-deficient genotype rec-1 ²⁶/rec-1 ¹⁶ by reducing or eliminating the synaptonemal complex. Measurements of the length of synaptonemal complexes in heat-treated and untreated stage 1 oocytes, following termination of the temperature-sensitive period, reveal less than a 5% difference, with the greater length present in the treated oocytes. Alterations are not observed in synaptonemal complex distribution within the nucleus or in its fine structure. Parallel genetic studies confirm earlier observations that the restrictive temperature, whose action is confined to a 36-h sensitive period virtually coextensive with premeiotic-S, drastically reduces recombination to 10% of normal. The results are most simply interpreted to mean that the restrictive temperatures acts directly on the recombination process.     

Linkage disequilibrium across two different single-nucleotide polymorphism genome scans

Linkage disequilibrium (LD) content was calculated for the Genetic Analysis Workshop 14 Affymetrix and Illumina single-nucleotide polymorphism (SNP) genome scans of the Collaborative Study on the Genetics of Alcoholism samples. Pair-wise LD was measured as both D' and r2 on 505 pedigree founder individuals. The r2 estimates were then used to correct the multipoint identity by descent matrix (MIBD) calculation to account for LD and LOD scores on chromosomes 3 and 18 were calculated for COGA's ttdt3 electrophysiological trait using those MIBDs. Extensive LD was observed throughout both marker sets, and it was higher in Affymetrix's more dense SNP map. However, SNP density did not solely account for Affymetrix's higher LD. MIBD estimation procedures assume linkage equilibrium to construct genotypes of non-genotyped pedigree founder individuals, and dense SNP genotyping maps are likely to contain moderate to high LD between markers. LOD score plots calculated after correction for LD followed the same general pattern as uncorrected ones. Since in our study almost half of the pedigree founders were genotyped, it is possible that LD had a minor impact on the LOD scores. Caution should probably be taken when using high density SNP maps when many non-genotyped founders are present in the study pedigrees.     

Seasonal changes in recombination characteristics in a natural population of Drosophila melanogaster

Environmental seasonality is a potent evolutionary force, capable of maintaining polymorphism, promoting phenotypic plasticity and causing bet-hedging. In Drosophila, environmental seasonality has been reported to affect life-history traits, tolerance to abiotic stressors and immunity. Oscillations in frequencies of alleles underlying fitness-related traits were also documented alongside SNPs across the genome. Here, we test for seasonal changes in two recombination characteristics, crossover rate and crossover interference, in a natural D. melanogaster population from India using morphological markers of the three major chromosomes. We show that winter flies, collected after the dry season, have significantly higher desiccation tolerance than their autumn counterparts. This difference proved to hold also for hybrids with three independent marker stocks, suggesting its genetic rather than plastic nature. Significant between-season changes are documented for crossover rate (in 9 of 13 studied intervals) and crossover interference (in four of eight studied pairs of intervals); both single and double crossovers were usually more frequent in the winter cohort. The winter flies also display weaker plasticity of both recombination characteristics to desiccation. We ascribe the observed differences to indirect selection on recombination caused by directional selection on desiccation tolerance. Our findings suggest that changes in recombination characteristics can arise even after a short period of seasonal adaptation (~8–10 generations).Subject terms: Structural variation, Evolutionary biology, Evolutionary genetics     

Linkage disequilibrium patterns and tagSNP transferability among European populations

The pattern of linkage disequilibrium (LD) is critical for association studies, in which disease-causing variants are identified by allelic association with adjacent markers. The aim of this study is to compare the LD patterns in several distinct European populations. We analyzed four genomic regions (in total, 749 kb) containing candidate genes for complex traits. Individuals were genotyped for markers that are evenly distributed at an average spacing of approximately 2-4 kb in eight population-based samples from ongoing epidemiological studies across Europe. The Centre d'Etude du Polymorphisme Humain (CEPH) trios of the HapMap project were included and were used as a reference population. In general, we observed a conservation of the LD patterns across European samples. Nevertheless, shifts in the positions of the boundaries of high-LD regions can be demonstrated between populations, when assessed by a novel procedure based on bootstrapping. Transferability of LD information among populations was also tested. In two of the analyzed gene regions, sets of tagging single-nucleotide polymorphisms (tagSNPs) selected from the HapMap CEPH trios performed surprisingly well in all local European samples. However, significant variation in the other two gene regions predicts a restricted applicability of CEPH-derived tagging markers. Simulations based on our data set show the extent to which further gain in tagSNP efficiency and transferability can be achieved by increased SNP density.