Linkage Analysis of the Multilocus Glucosephosphate Isomerase Isozyme System in Sunfish (Centrarchidae, Teleostii)

The purpose of the present investigation is to determine whether the two duplicated glucosephosphate isomerase (EC 5.3.1.9) loci Gpi-A and Gpi-B reside on the same chromosome in teleostean fishes. Interspecific sunfish hybrids were employed for the cross because of the different species-specific electrophoretic mobilities of the allelic isozymes at each GPI locus and because of their genomic compatibility. F1 sunfish hybrids, formed from a male warmouth (Lepomis gulosus) X female green sunfish (L. cyanellus) cross, were mated to form the F2 generation. The number of each of the nine different isozyme phenotypes, revealed by starch gel electrophoresis, was determined using 256 F2 individuals. The high frequency of recombinant phenotypes in the F2 generation indicated that the two GPI loci are not linked. An excess of F2 individuals heterozygous at both loci was observed and is interpreted as being caused by heterosis. The absence of linkage for the homologous loci encoding GPI subunits and for other multilocus isozyme systems is consistent with the postulate that the genomes of present-day vertebrates arose through one or more polyploidization events early in vertebrate evolution.     

Multilocus Behavior in Random Environments. II. Linkage Disequilibrium in an Additive Model

The effect of a stochastic environment on an additive, two-locus model of a diploid population is examined. The appropriate diffusion equation is derived and its asymptotic properties are approximated by an Orstein-Uhlenbeck process. The first and second order moments of this approximating process are given. The mean linkage disequilibrium will be nonzero if the alleles at the different loci are correlated. The sign of the mean disequilibrium is determined by the sign of the correlation.     

The Effects of Selection on Linkage Analysis for Quantitative Traits

The effects of within-sample selection on the outcome of analyses detecting linkage between genetic markers and quantitative traits were studied. It was found that selection by truncation for the trait of interest significantly reduces the differences between marker genotype means thus reducing the power to detect linked quantitative trait loci (QTL). The size of this reduction is a function of proportion selected, the magnitude of the QTL effect, recombination rate between the marker locus and the QTL, and the allele frequency of the QTL. Proportion selected was the most influential of these factors on bias, e.g., for an allele substitution effect of one standard deviation unit, selecting the top 80%, 50% or 20% of the population required 2, 6 or 24 times the number of progeny, respectively, to offset the loss of power caused by this selection. The effect on power was approximately linear with respect to the size of gene effect, almost invariant to recombination rate, and a complex function of QTL allele frequency. It was concluded that experimental samples from animal populations which have been subjected to even minor amounts of selection will be inefficient in yielding information on linkage between markers and loci influencing the quantitative trait under selection.     

Multilocus Patterns of Nucleotide Diversity, Population Structure and Linkage Disequilibrium in Boechera stricta, a Wild Relative of Arabidopsis

Information about polymorphism, population structure, and linkage disequilibrium (LD) is crucial for association studies of complex trait variation. However, most genomewide studies have focused on model systems, with very few analyses of undisturbed natural populations. Here, we sequenced 86 mapped nuclear loci for a sample of 46 genotypes of Boechera stricta and two individuals of B. holboellii, both wild relatives of Arabidopsis. Isolation by distance was significant across the species range of B. stricta, and three geographic groups were identified by structure analysis, principal coordinates analysis, and distance-based phylogeny analyses. The allele frequency spectrum indicated a genomewide deviation from an equilibrium neutral model, with silent nucleotide diversity averaging 0.004. LD decayed rapidly, declining to background levels in ~10 kb or less. For tightly linked SNPs separated by <1 kb, LD was dependent on the reference population. LD was lower in the specieswide sample than within populations, suggesting that low levels of LD found in inbreeding species such as B. stricta, Arabidopsis thaliana, and barley may result from broad geographic sampling that spans heterogeneous genetic groups. Finally, analyses also showed that inbreeding B. stricta and A. thaliana have ~45% higher recombination per kilobase than outcrossing A. lyrata.     

Toward a Wolbachia Multilocus Sequence Typing System: Discrimination of Wolbachia Strains Present in Drosophila Species

Among the diverse maternally inherited symbionts in arthropods, Wolbachia are the most common and infect over 20% of all species. In a departure from traditional genotyping or phylogenetic methods relying on single Wolbachia genes, the present study represents an initial Multilocus Sequence Typing (MLST) analysis to discriminate closely related Wolbachia pipientis strains, and additional data on sequence diversity in Wolbachia. We report a new phylogenetic characterization of four genes (aspC, atpD, sucB, and pdhB), and provide an expanded analysis of markers described in previous studies (16S rDNA, ftsZ, groEL, dnaA, and gltA). MLST analysis of the bacterial strains present in 16 different Drosophila–Wolbachia associations detected four distinct clonal complexes that also corresponded to maximum-likelihood identified phylogenetic clades. Among the 16 associations analyzed, six could not be assigned to MLST clonal complexes and were also shown to be in conflict with relationships predicted by maximum-likelihood phylogenetic inferences. The results demonstrate the discriminatory power of MLST for identifying strains and clonal lineages of Wolbachia and provide a robust foundation for studying the ecology and evolution of this widespread endosymbiont.     

Pleiotropic Overdominance and the Maintenance of Genetic Variation in Polygenic Characters

A model of selection is described in which optimizing phenotypic selection is combined with pleiotropic overdominance. Thus, the role that mutation commonly plays in models of phenotypic evolution is replaced by balancing selection. Expressions are provided for the equilibrium genetic variance in phenotype and for the heterozygosity. An approximate analysis of the transient properties of the model shows that, in certain circumstances, the behavior is quite similar to that of models based on the interaction of mutation and selection.     

Multilocus analysis of hypertension: a hierarchical approach

While hypertension is a complex disease with a well-documented genetic component, genetic studies often fail to replicate findings. One possibility for such inconsistency is that the underlying genetics of hypertension is not based on single genes of major effect, but on interactions among genes. To test this hypothesis, we studied both single locus and multilocus effects, using a case-control design of subjects from Ghana. Thirteen polymorphisms in eight candidate genes were studied. Each candidate gene has been shown to play a physiological role in blood pressure regulation and affects one of four pathways that modulate blood pressure: vasoconstriction (angiotensinogen, angiotensin converting enzyme - ACE, angiotensin II receptor), nitric oxide (NO) dependent and NO independent vasodilation pathways and sodium balance (G protein-coupled receptor kinase, GRK4). We evaluated single site allelic and genotypic associations, multilocus genotype equilibrium and multilocus genotype associations, using multifactor dimensionality reduction (MDR). For MDR, we performed systematic reanalysis of the data to address the role of various physiological pathways. We found no significant single site associations, but the hypertensive class deviated significantly from genotype equilibrium in more than 25% of all multilocus comparisons (2,162 of 8,178), whereas the normotensive class rarely did (11 of 8,178). The MDR analysis identified a two-locus model including ACE and GRK4 that successfully predicted blood pressure phenotype 70.5% of the time. Thus, our data indicate epistatic interactions play a major role in hypertension susceptibility. Our data also support a model where multiple pathways need to be affected in order to predispose to hypertension.     

Multilocus enzyme electrophoresis: a practical guide

Multilocus enzyme electrophoresis (MEE) uses the relative electrophoretic mobilities of intracellular enzymes to characterize and differentiate organisms by generating an electromorph type (ET). This article presents the chemical conditions that may be useful, a guide to the successful practice of the electrophoretic technique, and analysis of the results.     

用超显性模型估计遗传多态平衡的种群参数

基于超显性模型,采用数学方法阐述了种群遗传多样性的延续机制及平衡条件,从双等位基因导出的定律有较大的局限性,在许多教科书中常用的估计平衡态基因频数的定律只适用于双等位基因,本文用另一种方法导出一些公式,将其扩展到多等位基因,讨论了种群中基因数ｎ,遗传负载荷（Ｌ）,杂合频ＹＸ（Ｈｅ）和纯合频率（Ｈｏｍ）之间的关系。     

Multilocus Evolution in Fire Ants: Effects of Selection, Gene Flow and Recombination

The reproductive success of individual fire ant queens (Solenopsis invicta) previously has been shown to be strongly influenced by their genotype at a single enzyme-encoding gene, designated Pgm-3. This paper presents evidence that a second, tightly linked gene, designated Gp-9, is under similarly strong selection in these ants. Selection appears to act independently on the two genes and is detectable in only one of the two social forms of this species (the ``polygyne' social form, in which nests contain multiple fertile queens). Strong directional selection on Pgm-3 in this form involves worker destruction of all queens with genotype Pgm-3(AA) before they reproduce. Selection on Gp-9 is more complex, involving both lethality of all Gp-9(bb) females and a strong or even complete survival advantage to reproductive queens with the heterozygous genotype Gp-9(Bb). Pgm-3 and Gp-9 are tightly linked (r(f) = 0.0016) and exhibit strong gametic phase disequilibrium in introduced populations in the U.S. This disequilibrium seems not to have stemmed from the founder event associated with the introduction, because the same associations of alleles found in the U.S. apparently occur also in two native populations in Argentina. Rather, selection acting independently on Pgm-3 and Gp-9, in conjunction with gene flow from the alternate, ``monogyne' social form (in which nests contain a single fertile queen), may explain the origin of disequilibrium between the two loci in polygyne fire ants.     

The Admixture Linkage Disequilibrium and Genetic Linkage Inference on the Gradual Admixture Population

Through the theoretical analysis of the admixture linkage disequilibrium (ALD) in the gradual admixture (GA) model, in which admixture occurs in every generation, the ALD is found to be proportional to the difference in marker allele frequencies, p₁-p₂, between two subpopulations. Based on this property, we can employ a strict monotonic function (Δ_ker=Δ/(p₁-p₂), where Δ denotes the linkage disequilibrium (LD)) of the recombination fraction between the marker locus and the disease locus to infer the true genetic linkage. We construct a quasi likelihood ratio test (LRT) for the case-only data utilizing the information of unlinked markers in the human genome. The simulation results show that our tests can be used to fine map a disease locus. The effects of parameter values in the ALD mapping are also discussed.     

渐近混合群体的混合连锁不平衡及其遗传连锁推断

在渐近混合模型中,混合现象发生在每一世代,通过对其混合连锁不平衡的理论分析,发现混合连锁不平衡与两个子群体间的基因频率差成正比。基于这一点,构造了一个对重组率严格单调的函数（△ker=△／（p1-p2）,其中△代表连锁不平衡）,进而据此推断标记基因座与疾病基因座的遗传连锁。应用人类基因组上不连锁的标记基因提供的连锁不平衡信息,基于病人组数据构造了一个准似然比统计量。模拟结果显示,此检验可用于精确的基因定位。文章亦讨论了参数对检验的影响。     

Multilocus self-recognition systems in fungi as a cause of trans-species polymorphism

Trans-species polymorphism, meaning the presence of alleles in different species that are more similar to each other than they are to alleles in the same species, has been found at loci associated with vegetative incompatibility in filamentous fungi. If individuals differ at one or more of these loci (termed het for heterokaryon), they cannot form stable heterokaryons after vegetative fusion. At the het-c locus in Neurospora crassa and related species there is clear evidence of trans-species polymorphism: three alleles have persisted for approximately 30 million years. We analyze a population genetic model of multilocus vegetative incompatibility and find the conditions under which trans-species polymorphism will occur. In the model, several unlinked loci determine the vegetative compatibility group (VCG) of an individual. Individuals of different VCGs fail to form productive heterokaryons, while those of the same VCG form viable heterokaryons. However, viable heterokaryon formation between individuals of the same VCG results in a loss in fitness, presumably via transfer of infectious agents by hyphal fusion or exploitation by aggressive genotypes. The result is a form of balancing selection on all loci affecting an individual's VCG. We analyze this model by making use of a Markov chain/strong selection, weak mutation (SSWM) approximation. We find that trans-species polymorphism of the type that has been found at the het-c locus is expected to occur only when the appearance of new incompatibility alleles is strongly constrained, because the rate of mutation to such alleles is very low, because the number of possible incompatibility alleles at each locus is restricted, or because the number of incompatibility loci is limited.     

The Effects of Experimentally Induced Polyandry on Female Reproduction in a Monandrous Mating System

Females of most insect species maximize their fitness by mating more than once. Yet, some taxa are monandrous and there are two distinct scenarios for the maintenance of monandry. While males should always benefit from inducing permanent non‐receptivity to further mating in their mate, this is not necessarily true for females. Since females benefit from remating in many species, cases of monandry may reflect successful male manipulation of female remating (i.e. sexual conflict). Alternatively, monandry may favor both mates, if females maximize their fitness by mating only once in their life. These two hypotheses for the maintenance of monandry make contrasting predictions with regards to the effects of remating on female fitness. Here, we present an experimental test of the above hypotheses, using the monandrous housefly (Musca domestica) as a model system. Our results showed that accessory seminal fluid substances that males transfer to females during copulation have a dual effect: they trigger female non‐receptivity but also seem to have a nutritional effect that could potentially enhance female fitness. These results suggest that monandry is maintained in house flies despite potential benefits that females would gain by mating multiply.     

Effects of Overlapping Generations on Linkage Disequilibrium Estimates of Effective Population Size

Use of single-sample genetic methods to estimate effective population size has skyrocketed in recent years. Although the underlying models assume discrete generations, they are widely applied to age-structured species. We simulated genetic data for 21 iteroparous animal and plant species to evaluate two untested hypotheses regarding performance of the single-sample method based on linkage disequilibrium (LD): (1) estimates based on single-cohort samples reflect the effective number of breeders in one reproductive cycle (N_b), and (2) mixed-age samples reflect the effective size per generation (N_e). We calculated true N_e and N_b, using the model species’ vital rates, and verified these with individual-based simulations. We show that single-cohort samples should be equally influenced by N_b and N_e and confirm this with simulated results: N^b was a linear (r² = 0.98) function of the harmonic mean of N_e and N_b. We provide a quantitative bias correction for raw N^b based on the ratio N_b/N_e, which can be estimated from two or three simple life history traits. Bias-adjusted estimates were within 5% of true N_b for all 21 study species and proved robust when challenged with new data. Mixed-age adult samples produced downwardly biased estimates in all species, which we attribute to a two-locus Wahlund effect (mixture LD) caused by combining parents from different cohorts in a single sample. Results from this study will facilitate interpretation of rapidly accumulating genetic estimates in terms of both N_e (which influences long-term evolutionary processes) and N_b (which is more important for understanding eco-evolutionary dynamics and mating systems).     

Two Modes of Balancing Selection in Drosophila Melanogaster: Overcompensation and Overdominance

Overdominance is often invoked to account for the extensive polymorphisms found in natural populations of organisms; overcompensation, however, may be equally or more important. Overcompensation occurs when limiting resources are better exploited by a genetically mixed than by a uniform population, and is often causally related to frequency-dependent selection. We have designed experiments to test whether overcompensation occurs in Drosophila melanogaster, using the Sod locus as a marker. Tests are made at each of two densities and two temperatures for cultures with desired genetic compositions. Both temperature and density have statistically significant effects on the per-female productivity of the cultures. More important, there are strong effects due to overcompensation. Cultures that are more polymorphic are also more productive than less polymorphic ones even when the level of individual heterozygosity is the same in all. There is also overdominance for the Sod locus: the heterozygotes are more productive than either homozygote at every temperature and density, and the differences are statistically significant in several cases. These results corroborate previous studies showing that overdominance may contribute to the maintenance of the Sod polymorphisms. Moreover, our results indicate that the significance of overcompensation as a mechanism to account for polymorphism in natural populations deserves further investigation.     

The Direction of Linkage Disequilibrium

The previous paper (Langley, Tobari and Kojima 1974) reports that the directional linkage disequilibria, D_ω = P_ABP_ab-P_AbP_aB, tend to be negative for data between allozymes and linked to inversions. A and B stand for the two alleles with the greatest frequency in the population. In this paper we show that linkage disequilibrium in this direction is produced at equilibrium when double homozygotes have fitnesses that are a constant fraction of the product of the two component single homozygote fitnesses, a pattern that is frequently observed in experimental data.