Search PubMed⌕ Search

Biomedical subjects

M Turelli

Publications and source records attributed to M Turelli.

At least 19 recordsLinked to original sources
PubMed1999

Microbe-induced cytoplasmic incompatibility as a mechanism for introducing transgenes into arthropod populations.

Many arthropods are infected with maternally transmitted, intracellular bacteria of the genus Wolbachia. These infections often produce 'cytoplasmic incompatibility' (CI)--reduced egg-hatch frequencies when uninfected females mate with infected males or when males and females carrying different Wolbachia strains mate. Because infected females often enjoy a fitness advantage--they are effectively immune to any effects from males carrying the same Wolbachia strain--Wolbachia and associated cytoplasmic elements can spread rapidly through natural populations. Wolbachia might therefore drive transgenes associated with disease control or pest abatement into populations. In this paper, simple mathematical analyses are presented of three alternative strategies for 'CI drive'. The analyses reveal which parameters must be estimated in order to predict population dynamics, and they demonstrate stringent requirements for initially driving and/or maintaining transgenes in target populations.

Animals↗
PubMed1997

Multilocus evolutionarily stable strategy models: additive effects.

A common reservation about Evolutionarily Stable Strategy analyses is that they fail to account explicitly for Mendelian genetics, and therefore may produce biologically unfeasible predictions. This note shows that Evolutionarily Stable Strategy and multilocus genetic analyses agree for one simple model of frequency-dependent selection under the assumption that the effects of alleles and loci are completely additive. A numeric example illustrated the concepts and results involved.

Animals↗
PubMed1997

Haldane's rule and X-chromosome size in Drosophila.

The "dominance theory" of HALDANE'S rule postulates that hybrids of the heterogametic sex are more likely to be inviable or sterile than the homogametic sex because some of the epistatic incompatibilities contributing to postzygotic isolation behave as X-linked partial recessives. When this is true, pairs of taxa with relatively large X chromosomes should require less divergence time, on average, to produce HALDANE'S rule than pairs with smaller Xs. Similarly, if the dominance theory is correct and if the X chromosome evolves at a similar rate to the autosomes, the size of the X should not influence the rate at which homogametic hybrids become inviable or sterile. We use Drosophila data to examine both of these predictions. As expected under the dominance theory, pairs of taxa with large X chromosomes (approximately 40% of the nuclear genome) show HALDANE's rule for sterility at significantly smaller genetic distances than pairs with smaller X chromosomes (approximately 20% of the genome). As also predicted, the genetic distances between taxa that exhibit female inviability/sterility show no differences between "large X" vs. "small X" pairs. We present some simple mathematical models to relate these data to the dominance theory and alternative hypotheses involving faster evolution of the X vs. the autosomes and/or faster evolution of incompatibilities that produce male-specific vs. female-specific sterility. Although the data agree qualitatively with the predictions of the dominance theory, they depart significantly from the quantitative predictions of simple models of the dominance theory and the other hypotheses considered. These departures probably stem from the many simplifying assumptions needed to tractably model epistatic incompatibilities and to analyze heterogeneous data from many taxa.

Animals↗
PubMed1995

The kinetics of quantal transmitter release from retinal amacrine cells.

Exocytosis of transmitter at most synapses is a very fast process triggered by the entry of Ca2+ during an action potential. A reasonable expectation is that the fast step of exocytosis is followed by slow steps readying another vesicle for exocytosis but the identity and kinetics of these steps are presently unclear. By voltage clamping both pre- and postsynaptic neurons in an isolated pair of retinal amacrine cells, we have measured evoked synaptic currents and responses to single vesicles of transmitter (minis). From these currents, we have computed the rate of exocytosis during a sustained presynaptic depolarization. We show here that for these cells, release is consistent with a scheme of "fire and reload." Large Ca2+ influx causes the rapid release of a small number of vesicles, typically approximately 10 per presynaptic neuron, likely corresponding to those vesicles already docked. After this spike of exocytosis whose peak is 150 quanta per release site per s, continued Ca2+ influx sustains release at only 22 quanta per release site per s, probably rate-limited by the docking of fresh vesicles.

Animals↗
PubMed1995

The dominance theory of Haldane's rule.

"HALDANE's rule" states that, if species hybrids of one sex only are inviable or sterile, the afflicted sex is much more likely to be heterogametic (XY) than homogametic (XX). We show that most or all of the phenomena associated with HALDANE's rule can be explained by the simple hypothesis that alleles decreasing hybrid fitness are partially recessive. Under this hypothesis, the XY sex suffers more than the XX because X-linked alleles causing postzygotic isolation tend to have greater cumulative effects when hemizygous than when heterozygous, even though the XX sex carries twice as many such alleles. The dominance hypothesis can also account for the "large X effect," the disproportionate effect of the X chromosome on hybrid inviability/sterility. In addition, the dominance theory is consistent with: the long temporal lag between the evolution of heterogametic and homogametic postzygotic isolation, the frequency of exceptions to HALDANE's rule, puzzling Drosophila experiments in which "unbalanced" hybrid females, who carry two X chromosomes from the same species, remain fertile whereas F1 hybrid males are sterile, and the absence of cases of HALDANE's rule for hybrid inviability in mammals. We discuss several novel predictions that could lead to rejection of the dominance theory.

Alleles↗
PubMed1995

Cytoplasmic incompatibility in Drosophila simulans: dynamics and parameter estimates from natural populations.

In Drosophila simulans, cytoplasmically transmitted Wolbachia microbes cause reduced egg hatch when infected males mate with uninfected females. A Wolbachia infection and an associated mtDNA variant have spread northward through California since 1986. PCR assays show that Wolbachia infection is prevalent throughout the continental US and Central and South America, but some lines from Florida and Ecuador that are PCR-positive for Wolbachia do not cause incompatibility. We estimate from natural populations infection frequencies and the transmission and incompatibility parameter values that affect the spread of the infection. On average, infected females from nature produce 3-4% uninfected ova. Infected females with relatively low fidelity of maternal transmission show partial incompatibility with very young infected laboratory males. Nevertheless, crosses between infected flies in nature produce egg-hatch rates indistinguishable from those produced by crosses between uninfected individuals. Incompatible crosses in nature produce hatch rates 30-70% as high as those from compatible crosses. Wild-caught infected and uninfected females are equally fecund in the laboratory. Incompatibility decreases with male age, and age-specific incompatibility levels suggest that males mating in nature may often be 2 or 3 weeks old. Our parameter estimates accurately predict the frequency of Wolbachia infection in California populations.

Africa, Southern↗
PubMed1994

Genetic and statistical analyses of strong selection on polygenic traits: what, me normal?

We develop a general population genetic framework for analyzing selection on many loci, and apply it to strong truncation and disruptive selection on an additive polygenic trait. We first present statistical methods for analyzing the infinitesimal model, in which offspring breeding values are normally distributed around the mean of the parents, with fixed variance. These show that the usual assumption of a Gaussian distribution of breeding values in the population gives remarkably accurate predictions for the mean and the variance, even when disruptive selection generates substantial deviations from normality. We then set out a general genetic analysis of selection and recombination. The population is represented by multilocus cumulants describing the distribution of haploid genotypes, and selection is described by the relation between mean fitness and these cumulants. We provide exact recursions in terms of generating functions for the effects of selection on non-central moments. The effects of recombination are simply calculated as a weighted sum over all the permutations produced by meiosis. Finally, the new cumulants that describe the next generation are computed from the non-central moments. Although this scheme is applied here in detail only to selection on an additive trait, it is quite general. For arbitrary epistasis and linkage, we describe a consistent infinitesimal limit in which the short-term selection response is dominated by infinitesimal allele frequency changes and linkage disequilibria. Numerical multilocus results show that the standard Gaussian approximation gives accurate predictions for the dynamics of the mean and genetic variance in this limit. Even with intense truncation selection, linkage disequilibria of order three and higher never cause much deviation from normality. Thus, the empirical deviations frequently found between predicted and observed responses to artificial selection are not caused by linkage-disequilibrium-induced departures from normality. Disruptive selection can generate substantial four-way disequilibria, and hence kurtosis; but even then, the Gaussian assumption predicts the variance accurately. In contrast to the apparent simplicity of the infinitesimal limit, data suggest that changes in genetic variance after 10 or more generations of selection are likely to be dominated by allele frequency dynamics that depend on genetic details.

Fourier Analysis↗
PubMed1992

Deleterious mutations, apparent stabilizing selection and the maintenance of quantitative variation.

Apparent stabilizing selection on a quantitative trait that is not causally connected to fitness can result from the pleiotropic effects of unconditionally deleterious mutations, because as N. Barton noted, "...individuals with extreme values of the trait will tend to carry more deleterious alleles...." We use a simple model to investigate the dependence of this apparent selection on the genomic deleterious mutation rate, U; the equilibrium distribution of K, the number of deleterious mutations per genome; and the parameters describing directional selection against deleterious mutations. Unlike previous analyses, we allow for epistatic selection against deleterious alleles. For various selection functions and realistic parameter values, the distribution of K, the distribution of breeding values for a pleiotropically affected trait, and the apparent stabilizing selection function are all nearly Gaussian. The additive genetic variance for the quantitative trait is kQa2, where k is the average number of deleterious mutations per genome, Q is the proportion of deleterious mutations that affect the trait, and a2 is the variance of pleiotropic effects for individual mutations that do affect the trait. In contrast, when the trait is measured in units of its additive standard deviation, the apparent fitness function is essentially independent of Q and a2; and beta, the intensity of selection, measured as the ratio of additive genetic variance to the "variance" of the fitness curve, is very close to s = U/k, the selection coefficient against individual deleterious mutations at equilibrium. Therefore, this model predicts appreciable apparent stabilizing selection if s exceeds about 0.03, which is consistent with various data. However, the model also predicts that beta must equal Vm/VG, the ratio of new additive variance for the trait introduced each generation by mutation to the standing additive variance. Most, although not all, estimates of this ratio imply apparent stabilizing selection weaker than generally observed. A qualitative argument suggests that even when direct selection is responsible for most of the selection observed on a character, it may be essentially irrelevant to the maintenance of variation for the character by mutation-selection balance. Simple experiments can indicate the fraction of observed stabilizing selection attributable to the pleiotropic effects of deleterious mutations.

Alleles↗
PubMed1992

Dynamics of cytoplasmic incompatibility and mtDNA variation in natural Drosophila simulans populations.

In Drosophila simulans a cytoplasmically transmitted microorganism causes reduced egg hatch when infected males mate with uninfected females. The infection is rapidly spreading northward in California. Data on a specific mtDNA restriction site length polymorphism show that changes in the frequency of mtDNA variants are associated with this spread. All infected flies possess the same mtDNA allele, whereas the uninfected flies are polymorphic. Given that both paternal inheritance of the infection and imperfect maternal transmission have been demonstrated, one might expect instead that both infected and uninfected flies would possess both mtDNA variants. Our data suggest that imperfect female transmission of the infection (and/or the loss of the infection among progeny) is more common in nature than paternal transmission. A simple model of intrapopulation dynamics, with empirically supported parameter values, adequately describes the joint frequencies of the mtDNA variants and incompatibility types.

Animals↗
PubMed1991

Rapid spread of an inherited incompatibility factor in California Drosophila.

In Drosophila simulans in California, an inherited cytoplasmic incompatibility factor reduces egg hatch when infected males mate with uninfected females. The infection is spreading at a rate of more than 100 km per year; populations in which the infection was rare have become almost completely infected within three years. Analyses of the spread using estimates of selection in the field suggest dispersal distances far higher than those found by direct observation of flies. Hence, occasional long-distance dispersal, possibly coupled with local extinction and recolonization, may be important to the dynamics. Incompatibility factors that can readily spread through natural populations may be useful for population manipulation and important as a post-mating isolating mechanism.

Animals↗
PubMed1991

Natural and sexual selection on many loci.

A method is developed that describes the effects on an arbitrary number of autosomal loci of selection on haploid and diploid stages, of nonrandom mating between haploid individuals, and of recombination. We provide exact recursions for the dynamics of allele frequencies and linkage disequilibria (nonrandom associations of alleles across loci). When selection is weak relative to recombination, our recursions provide simple approximations for the linkage disequilibria among arbitrary combinations of loci. We show how previous models of sex-independent natural selection on diploids, assortative mating between haploids, and sexual selection on haploids can be analyzed in this framework. Using our weak-selection approximations, we derive new results concerning the coevolution of male traits and female preferences under natural and sexual selection. In particular, we provide general expressions for the intensity of linkage-disequilibrium induced selection experienced by loci that contribute to female preferences for specific male traits. Our general results support the previous observation that these indirect selection forces are so weak that they are unlikely to dominate the evolution of preference-producing loci.

Animals↗
PubMed1990

Factors affecting the distribution of cytoplasmic incompatibility in Drosophila simulans.

In Drosophila simulans a Wolbachia-like microorganism is responsible for reduced egg-hatch when infected males mate with uninfected females. Both incompatibility types have previously been found in North America, Europe and Africa. Some California populations have remained polymorphic for over two years, and the infection is apparently spreading in central California. Egg hatch proportions for wild-caught females from polymorphic populations show that the incompatibility system acts in nature, but egg mortality rates are apparently lower than observed in laboratory populations. Although infected females maintained under various laboratory conditions never produce uninfected offspring, some wild-caught infected females produce both infected and uninfected progeny. This helps explain the persistence of a low frequency of uninfected flies in predominantly infected populations and may also explain the other polymorphisms observed. Fitness comparisons of infected and uninfected stocks, including both larval and adult fitness components, indicate that fecundity may be the component most affected. Infected females suffer a fecundity reduction of 10-20% in the laboratory, but the reduction seems to be smaller in nature. A theoretical analysis provides some insight into the population biology of the infection.

Aging↗
PubMed1989

Laboratory estimates of heritabilities and genetic correlations in nature.

A lower bound on heritability in a natural environment can be determined from the regression of offspring raised in the laboratory on parents raised in nature. An estimate of additive genetic variance in the laboratory is also required. The estimated lower bounds on heritabilities can sometimes be used to demonstrate a significant genetic correlation between two traits in nature, if their genetic and phenotypic correlations in nature have the same sign, and if sample sizes are large, and heritabilities and phenotypic and genetic correlations are high.

Animals↗