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A García-Dorado

Publications and source records attributed to A García-Dorado.

At least 19 recordsLinked to original sources
PubMed2005

The effect of antagonistic pleiotropy on the estimation of the average coefficient of dominance of deleterious mutations.

We investigate the impact of antagonistic pleiotropy on the most widely used methods of estimation of the average coefficient of dominance of deleterious mutations from segregating populations. A proportion of the deleterious mutations affecting a given studied fitness component are assumed to have an advantageous effect on another one, generating overdominance on global fitness. Using diffusion approximations and transition matrix methods, we obtain the distribution of gene frequencies for nonpleiotropic and pleiotropic mutations in populations at the mutation-selection-drift balance. From these distributions we build homozygous and heterozygous chromosomes and assess the behavior of the estimators of dominance. A very small number of deleterious mutations with antagonistic pleiotropy produces substantial increases on the estimate of the average degree of dominance of mutations affecting the fitness component under study. For example, estimates are increased three- to fivefold when 2% of segregating loci are over-dominant for fitness. In contrast, strengthening pleiotropy, where pleiotropic effects are assumed to be also deleterious, has little effect on the estimates of the average degree of dominance, supporting previous results. The antagonistic pleiotropy model considered, applied under mutational parameters described in the literature, produces patterns for the distribution of chromosomal viabilities, levels of genetic variance, and homozygous mutation load generally consistent with those observed empirically for viability in Drosophila melanogaster.

Computer Simulation↗
PubMed2005

Inferences on the role of insertion in a mutation accumulation experiment with Drosophila melanogaster using RAPDs.

The genetic variability for RAPDs band pattern was studied in a set of 157 mutation accumulation (MA) lines of Drosophila melanogaster. These MA lines were derived from the same isogenic base population and subsequently maintained by full-sib mating during 132 generations. The ancestral pattern of the original isogenic base can be unambiguously established as the consensus pattern of the MA lines and, because these lines are expected to be homozygous, dominance for band pattern is not a concern. Only repeatable changes in band pattern were considered. The number of ancestral bands detected implies that nine-nucleotide targets are enough for repeatable PCR amplification. Compared with the ancestral pattern, one MA line lost one band and two MA lines gained a new one. These results can be accounted for by the insertion of transposable elements occurring at a rate 0.07 < i < 0.21 per whole haploid genome and generation. This range is typical for Drosophila and consistent with the previously observed mobility for the roo family, supporting the generality of previous estimates of spontaneous mutation rates for morphological and fitness traits based on these MA lines. The sequence of one of the new bands suggests that the Idefix family is also active in the lines.

Animals↗
PubMed2005

A measure of the within-chromosome synergistic epistasis for Drosophila viability.

In order to detect possible synergistic epistasis for viability in Drosophila melanogaster we assayed the relative viability of chromosomes II in: (i) panmixia, (ii) forced total homozygosity, and (iii) homozygosity for, on the average, half of their loci. As these genotypes were constructed using exactly the same set of chromosomes in the three cases, the design allows us to estimate the inbreeding depression rate at two different inbreeding levels in the absence of purging natural selection. Overall, no consistent synergistic epistasis was found. However, there was a small fraction of chromosomes whose severely deleterious effect when homozygous was almost significantly larger than expected from their viability when homozygous for half of their loci. This suggests occasional but important synergistic epistasis, which might confer evolutionary advantage to recombination in tightly linked genomes. Nevertheless, such epistasis is unlikely to be an evolutionary advantage driving the evolution of sexual anisogamous reproduction, as its contribution to overall viability is small when compared with the two-fold cost of anisogamy.

Analysis of Variance↗
PubMed2004

Analysis of the estimators of the average coefficient of dominance of deleterious mutations.

We investigate the sources of bias that affect the most commonly used methods of estimation of the average degree of dominance (h) of deleterious mutations, focusing on estimates from segregating populations. The main emphasis is on the effect of the finite size of the populations, but other sources of bias are also considered. Using diffusion approximations to the distribution of gene frequencies in finite populations as well as stochastic simulations, we assess the behavior of the estimators obtained from populations at mutation-selection-drift balance under different mutational scenarios and compare averages of h for newly arisen and segregating mutations. Because of genetic drift, the inferences concerning newly arisen mutations based on the mutation-selection balance theory can have substantial upward bias depending upon the distribution of h. In addition, estimates usually refer to h weighted by the homozygous deleterious effect in different ways, so that inferences are complicated when these two variables are negatively correlated. Due to both sources of bias, the widely used regression of heterozygous on homozygous means underestimates the arithmetic mean of h for segregating mutations, in contrast to their repeatedly assumed equality in the literature. We conclude that none of the estimators from segregating populations provides, under general conditions, a useful tool to ascertain the properties of the degree of dominance, either for segregating or for newly arisen deleterious mutations. Direct estimates of the average h from mutation-accumulation experiments are shown to suffer some bias caused by purging selection but, because they do not require assumptions on the causes maintaining segregating variation, they appear to give a more reliable average dominance for newly arisen mutations.

Computer Simulation↗
PubMed2002

The mutational rate of Drosophila viability decline: tinkering with old data.

In the first 25 generations of his classical mutation accumulation experiment, T. Mukai estimated a large rate of early linear decay for the relative viability of Drosophila melanogaster chromosome II (delta MII = 0.004). Mukai forced through zero the regression of viability decline on generation number, but it has recently been shown (Fry, 2001) that a similar decline (delta MII = 0.006) is obtained from unforced regression even if generation 32 instead of generation 25 (whose validity has been questioned) is included. We show that, from the perspective of the whole long-term experiment. it is hard to decide up to which generation viability can be considered to decline linearly. Depending on this decision, and on whether or not the regression is forced through the origin, very different estimates are obtained. Furthermore, the particular behaviour of the lines used as control suggests that they could have been different from the remaining lines at the beginning of the experiment, and casts doubts on the adequacy of a forced regression. Estimates from the linear unforced regression (delta MII = 0.011) or from the linear term in a quadratic unforced regression (delta MII = 0.001) are very different. The data fit both models very well, and the choice between them should be based on biological grounds.

Animals↗
PubMed2002

Accumulation of deleterious mutations: additional Drosophila melanogaster estimates and a simulation of the effects of selection.

We report an assay of egg-to-adult viability in full-sibling mutation accumulation (MA) lines derived from a completely homozygous population of Drosophila melanogaster and maintained for 210 generations. A simultaneous evaluation was also made of a large population derived from the same origin and maintained as a control for the same period. We also present computer simulations to explore the possible decline in viability of the control population due to mutation accumulation and the possible effect of selection within and between MA lines. For this purpose, we used two mutational models independent from the data analyzed and based on radically different assumptions. The first model implies a large number of mutations of small effect, whereas the second implies a much smaller number of mutations with much larger effects. The observed rate of decline in mean viability was very small but significant (0.077%). The rate of increase in among line variance (0.189 x 10(-3)) was similar to those obtained previously in the same lines. The simulation results indicated that a model of many mutations of small effect is incompatible with the evolution of the mean viability of the control and MA lines over generations, the distribution of line means after 210 generations of mutation accumulation, and the pattern of line extinction over generations. Basically, this model predicted a large drop in viability, both in the control and particularly the MA lines, that is not observed empirically. It also predicted a rate of line extinction too low in the early generations and too high in the later ones. In contrast, the model based on few mutations of large effect was generally consistent with all the observations.

Animals↗
PubMed2001

The rate of mutation and the homozygous and heterozygous mutational effects for competitive viability: a long-term experiment with Drosophila melanogaster.

The effect of 250 generations of mutation accumulation (MA) on the second chromosome competitive viability of Drosophila melanogaster was analyzed both in homozygous and heterozygous conditions. We used full-sib MA lines, where selection hampers the accumulation of severely deleterious mutations but is ineffective against mildly deleterious ones. A large control population was simultaneously evaluated. Competitive viability scores, unaffected by the expression of mutations in heterozygosis, were obtained relative to a Cy/L(2) genotype. The rate of decline in mean DeltaM approximately 0.1% was small. However, that of increase in variance DeltaV approximately 0.08 x 10(-3) was similar to the values obtained in previous experiments when severely deleterious mutations were excluded. The corresponding estimates of the mutation rate lambda > or = 0.01 and the average effect of mutations E(s) < or = 0.08 are in good agreement with Bateman-Mukai and minimum distance estimates for noncompetitive viability obtained from the same MA lines after 105 generations. Thus, competitive and noncompetitive viability show similar mutational properties. The regression estimate of the degree of dominance for mild-to-moderate deleterious mutations was approximately 0.3, suggesting that the pertinent value for new unselected mutations should be somewhat smaller.

Animals↗
PubMed2000

Temporal uniformity of the spontaneous mutational variance of quantitative traits in Drosophila melanogaster.

Spontaneous mutations were allowed to accumulate over 209 generations in more than 100 lines, all of them independently derived from a completely homozygous population of Drosophila melanogaster and subsequently maintained under strong inbreeding (equivalent to full-sib mating). Traits scored were: abdominal (AB) and sternopleural (ST) bristle number, wing length (WL) and egg-to-adult viability (V). On two occasions--early (generations 93-122) and late (generations 169-209)--ANOVA estimates of the mutational variance and the mutational line x generation interaction variance were obtained. Mutational heritabilities of morphological traits ranged from 2 x 10(-4) to 2 x 10(-3) and the mutational coefficient of variation of viability was 0.01. For AB, WL and V, temporal uniformity of the mutational variance was observed. However, a fluctuation of the mutational heritability of ST was detected and could be ascribed to random genotype x environment interaction.

Animals↗
PubMed2000

On the average coefficient of dominance of deleterious spontaneous mutations.

T. Mukai and co-workers in the late 1960s and O. Ohnishi in the 1970s carried out a series of experiments to obtain direct estimates of the average coefficient of dominance (h) of minor viability mutations in Drosophila melanogaster. The results of these experiments, although inconsistent, have been interpreted as indicating slight recessivity of deleterious mutations, with h approximately 0.4. Mukai obtained conflicting results depending on the type of heterozygotes used, some estimates suggesting overdominance and others partial dominance. Ohnishi's estimates, based on the ratio of heterozygous to homozygous viability declines, were more consistent, pointing to the above value. However, we have reanalyzed Ohnishi's data, estimating h by the regression method, and obtained a much smaller estimate of approximately 0.1. This significant difference can be due partly to the different weighting implicit in the estimates, but we suggest that this is not the only explanation. We propose as a plausible hypothesis that a putative nonmutational decline in viability occurring in the first half of Ohnishi's experiment (affecting both homozygotes and heterozygotes) has biased upward the estimates from the ratio, while it would not bias the regression estimates. This hypothesis also explains the very high h approximately 0.7 observed in Ohnishi's high-viability chromosomes. By constructing a model of spontaneous mutations using parameters in the literature, we investigate the above possibility. The results indicate that a model of few mutations with moderately large effects and h approximately 0.2 is able to explain the observed estimates and the distributions of homozygous and heterozygous viabilities. Accounting for an expression of mutations in genotypes with the balancer chromosome Cy does not alter the conclusions qualitatively.

Animals↗
PubMed1999

Properties of spontaneous mutations affecting quantitative traits.

Recent mutation accumulation results from invertebrate species suggest that mild deleterious mutation is far less frequent than previously thought, implying smaller expressed mutational loads. Although the rate (lambda) and effect (s) of very slight deleterious mutation remain unknown, most mutational fitness decline would come from moderately deleterious mutation (s approximately 0.2, lambda approximately 0.03), and this situation would not qualitatively change in harsh environments. Estimates of the average coefficient of dominance (h) of non-severe deleterious mutations are controversial. The typical value of h = 0.4 can be questioned, and a lower estimate (about 0.1) is suggested. Estimated mutational parameters are remarkably alike for morphological and fitness component traits (excluding lethals), indicating low mutation rates and moderate mutational effects, with a distribution generally showing strong negative asymmetry and little leptokurtosis. New mutations showed considerable genotype-environment interaction. However, the mutational variance of fitness-component traits due to non-severe detrimental mutations did not increase with environmental harshness. For morphological traits, a class of predominantly additive mutations with no detectable effect on fitness and relatively small effect on the trait was identified. This should be close to that responsible for standing variation in natural populations.

Adaptation, Physiological↗
PubMed1998

Population genetics: surviving under mutation pressure.

Concern has been voiced about the survival of endangered species, and even the long-term prospects for humans, in the face of accumulating deleterious mutations. Two experiments have investigated the mutation accumulation process in laboratory Drosophila populations, with apparently conflicting results.

Animals↗
PubMed1998

The mutation rate and the distribution of mutational effects of viability and fitness in Drosophila melanogaster.

The empirical distributions of the average viability and fitness of mutation accumulation lines of Drosophila melanogaster were analyzed using minimum distance estimation. Data come from two different experimental designs where mutations were allowed to accumulate: 1) in copies of chromosome II protected from natural selection and recombination (viability: Mukai et al., 1972; Ohnishi, 1977; fitness: Houle et al., 1992), 2) in inbred lines derived from the same isogenic stock (viability: Fernández & López-Fanjul, 1996; fitness: this paper). Information from all data sets converged, indicating that the mutational rates were small, about 1% for viability and 3% for fitness. For both traits, the rate of mutational decline appears to be smaller than suggested by previous studies (about one-fifth of the latter), the average mutational effect was neither severe nor very slight, ranging from -0.1 to -0.3, and the distribution of mutant effects was, at most, slightly leptokurtic. Therefore, the mutational load in natural populations is one to two orders of magnitude smaller than previously thought (as based upon analyses conditional to estimates of the mutational decline of viability or fitness that appear to be biased upward). Over 95% of the mutational variance of each trait was contributed by non-slightly deleterious mutations (absolute homozygous effect larger than 0.03 or 0.1, depending on the data set considered) occurring at a rate not higher than 0.025 per haploid genome and generation. Our data suggest that most deleterious mutations affecting fitness act mainly through a single component-trait.

Animals↗
PubMed1998

Minimum distance estimation of mutational parameters for quantitative traits.

Individual spontaneous mutations affecting the expression of quantitative traits cannot be systematically identified and, therefore, their effect on the trait cannot be measured. Thus, the rate of occurrence of such mutations and the moments of the probability distribution of the corresponding effects, which are important in evolutionary studies, remain unknown. Here we propose a method to estimate those mutational properties from the observed distribution of the trait mean in a set of independent inbred lines (all derived from the same homozygous base population) in which mutations had been allowed to accumulate randomly. It is based on the use of the well-known minimum distance method, i.e., on the minimization of a distance between the observed distribution and that expected on the basis of a genetic model. We analyze data for three morphological traits (wing length and abdominal and sternopleural bristle number) in Drosophila melanogaster. The method appears to be powerful, giving evolutionary coherent estimates of relevant mutational properties that had not been estimated previously. For all traits, mutational rates were low (smaller than 0.05). Most mutations affecting wing length or abdominal bristle number and negative effect, while almost half of those affecting sternopleural bristle number had positive effect. For each trait, results obtained from data on different generations are in qualitative agreement, although mutational effects seem to depend on generation-specific environmental factors. The method detected between-trait differences in the kurtosis coefficient of the distribution of mutational effects, which varied from values close to that of the normal distribution (wing length) to relatively high values (sternopleural bristle number). It reveals that an important proportion of the mutational input variance of each trait is due to mutations with absolute effect smaller than 0.5 environmental standard deviation units. For morphological traits undergoing weak direct selection, this suggests that large amounts of genetic variance due to genes segregating at intermediate frequencies can be present at the equilibrium.

Animals↗
PubMed1993

Filling a gap in the prediction of the equilibrium genetic variance.

We derive analytical predictions for the variance and kurtosis of the equilibrium distribution of allelic effects under stabilizing selection and drift, and for any value of the kurtosis of the distribution of the mutational effects. Numerical results relative to the equilibrium genetic variance are compared with other analytical predictions and with simulation results from the literature. Our prediction is superior for relatively weak selection (or relatively low variance of the mutational effects) and not to small population sizes, where previous methods overestimate the equilibrium genetic variance. The behavior of the equilibrium kurtosis is also illustrated.

Alleles↗
PubMed1991

Soft selection and quantitative genetic variation: a laboratory experiment.

The effect of environmental heterogeneity on the genetic variation of different quantitative characters was studied in two laboratory and two recently captured populations of Drosophila melanogaster. Two different culture media (habitats R and G) were used. Coarse-grained heterogeneity with independent density control in each habitat (R + G), and fine-grained (R/G) heterogeneity were simulated in population cages. Control populations in both R and G habitats were also maintained. Genetic differences for oviposition-site preference, larval preference and/or within-habitat viability were found between subpopulations sampled from different media. This happened in all four populations maintained on R + G, two populations maintained on R/G, and one control population. Thus, environmental heterogeneity seems to protect genetic variability responsible for between-habitat genetic differentiation, particularly when such heterogeneity corresponds to the 'soft selection' model (R + G). However, for the quasi-neutral trait sternopleural bristle number, no genetic between-habitat differentiation, nor increased heritability were observed in populations maintained under any kind of environmental heterogeneity. Hence, although soft selection seems to be a real force in determining adaptation to heterogeneous environments, the genetic variability maintained may be small in relation to the whole genome.

Animals↗
PubMed1990

Some evolutionary properties of parental investment per offspring in a heterogeneous environment.

The possibility of protected polymorphisms and of monomorphic evolutionarily stable strategies for parental investment per offspring in a heterogeneous environment is theoretically analysed. A high density two-niche model of the classical soft selection kind is used, although it incorporates the possibility of rare strategies invading an empty niche the contribution of which is not constant. Protected polymorphisms can be found whether or not both strategies included produce surviving offspring in both niches. However, a monomorphic evolutionarily stable strategy exists unless offspring of the optimal size in one of the niches cannot survive in the other. The robustness of the model is graphically illustrated under a variety of circumstances, and some evolutionary consequences are briefly discussed.

Animals↗
PubMed1985

Mitral valve prolapse secondary to right ventricular enlargement in patients with pulmonary hypertension after toxic rapeseed oil ingestion.

A high incidence of mitral valve prolapse (MVP) has been reported in various entities which produce important right ventricular (RV) enlargement with normal or decreased left ventricular (LV) volume. To evaluate the importance of RV enlargement in the genesis of MVP in these cases, we analyzed the echocardiographic studies from 176 patients with 'Síndrome Tóxico'. These patients underwent M-mode, cross-sectional and pulsed Doppler examination because of the suspicion of having dietary pulmonary hypertension, a complication which occurred in almost 20% of patients with this epidemic poisoning and which showed a course of gradual resolution in most of them. RV size was classified according to the RV/LV maximal short-axis dimension ratio as normal, border-line, moderately enlarged and severely enlarged. MPV was diagnosed according to standard M-mode and cross-sectional echocardiographic criteria. A second echocardiographic examination was obtained in 38 patients 12.5 +/- 5.3 months after the first one. The incidence of MVP was 9.3% in patients with normal RV size (N = 107), 9.5% in patients with border-line RV size (N = 23), 30% in patients with moderate RV enlargement (N = 30) and 56% in patients with severe RV enlargement (N = 16) (P less than 0.001). Fourteen (77%) of the 18 patients with MVP and moderate or severe RV enlargement (N = 16) (P less than 0.001). Fourteen (77%) of the 18 patients with MVP and moderate or severe RV enlargement had holosystolic MVP. At pulsed Doppler examination, no patient showed signs of mitral regurgitation.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗