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James D Fry

Publications and source records attributed to James D Fry.

7 recordsLinked to original sources
PubMed2006

Aldehyde dehydrogenase is essential for both adult and larval ethanol resistance in Drosophila melanogaster.

The enzyme aldehyde dehydrogenase (ALDH) is essential for ethanol metabolism in mammals, converting the highly toxic intermediate acetaldehyde to acetate. The role of ALDH in Drosophila has been debated, with some authors arguing that, at least in larvae, acetaldehyde detoxification is carried out mainly by alcohol dehydrogenase (ADH), the enzyme responsible for converting ethanol to acetaldehyde. Here, we report the creation and characterization of four null mutants of Aldh, the putative structural locus for ALDH. Aldh null larvae and adults are poisoned by ethanol concentrations easily tolerated by wild-types; their ethanol sensitivity is in fact comparable to that of Adh nulls. The results refute the view that ALDH plays only a minor role in ethanol detoxification in larvae, and suggest that Aldh and Adh may be equally important players in the evolution of ethanol resistance in fruit-breeding Drosophila.

Alcohol Dehydrogenase↗
PubMed2005

Widespread correlations between dominance and homozygous effects of mutations: implications for theories of dominance.

The dominance of deleterious mutations has important consequences for phenomena such as inbreeding depression, the evolution of diploidy, and levels of natural genetic variation. Kacser and Burns' metabolic theory provides a paradigmatic explanation for why most large-effect mutations are recessive. According to the metabolic theory, the recessivity of large-effect mutations is a consequence of a diminishing-returns relationship between flux through a metabolic pathway and enzymatic activity at any step in the pathway, which in turn is an inevitable consequence of long metabolic pathways. A major line of support for this theory was the demonstration of a negative correlation between homozygous effects and dominance of mutations in Drosophila, consistent with a central prediction of the metabolic theory. Using data on gene deletions in yeast, we show that a negative correlation between homozygous effects and dominance of mutations exists for all major categories of genes analyzed, not just those encoding enzymes. The relationship between dominance and homozygous effects is similar for duplicated and single-copy genes and for genes whose products are members of protein complexes and those that are not. A complete explanation of dominance therefore requires either a generalization of Kacser and Burns' theory to nonenzyme genes or a new theory.

Gene Deletion↗
PubMed2004

On the rate and linearity of viability declines in Drosophila mutation-accumulation experiments: genomic mutation rates and synergistic epistasis revisited.

High rates of deleterious mutations could severely reduce the fitness of populations, even endangering their persistence; these effects would be mitigated if mutations synergize each others' effects. An experiment by Mukai in the 1960s gave evidence that in Drosophila melanogaster, viability-depressing mutations occur at the surprisingly high rate of around one per zygote and that the mutations interact synergistically. A later experiment by Ohnishi seemed to support the high mutation rate, but gave no evidence for synergistic epistasis. Both of these studies, however, were flawed by the lack of suitable controls for assessing viability declines of the mutation-accumulation (MA) lines. By comparing homozygous viability of the MA lines to simultaneously estimated heterozygous viability and using estimates of the dominance of mutations in the experiments, I estimate the viability declines relative to an appropriate control. This approach yields two unexpected conclusions. First, in Ohnishi's experiment as well as in Mukai's, MA lines showed faster-than-linear declines in viability, indicative of synergistic epistasis. Second, while Mukai's estimate of the genomic mutation rate is supported, that from Ohnishi's experiment is an order of magnitude lower. The different results of the experiments most likely resulted from differences in the starting genotypes; even within Mukai's experiment, a subset of MA lines, which I argue probably resulted from a contamination event, showed much slower viability declines than did the majority of lines. Because different genotypes may show very different mutational behavior, only studies using many founding genotypes can determine the average rate and distribution of effects of mutations relevant to natural populations.

Animals↗
PubMed2003

Dominance of mutations affecting viability in Drosophila melanogaster.

There have been several attempts to estimate the average dominance (ratio of heterozygous to homozygous effects) of spontaneous deleterious mutations in Drosophila melanogaster, but these have given inconsistent results. We investigated whether transposable element (TE) insertions have higher average dominance for egg-to-adult viability than do point mutations, a possibility suggested by the types of fitness-depressing effects that TEs are believed to have. If so, then variation in dominance estimates among strains and crosses would be expected as a consequence of variation in TE activity. As a first test, we estimated the average dominance of all mutations and of copia insertions in a set of lines that had accumulated spontaneous mutations for 33 generations. A traditional regression method gave a dominance estimate for all mutations of 0.17, whereas average dominance of copia insertions was 0.51; the difference between these two estimates approached significance (P = 0.08). As a second test, we reanalyzed Ohnishi 1974 data on dominance of spontaneous and EMS-induced mutations. Because a considerable fraction of spontaneous mutations are caused by TE insertions, whereas EMS induces mainly point mutations, we predicted that average dominance would decline with increasing EMS concentration. This pattern was observed, but again fell short of formal significance (P = 0.07). Taken together, however, the two results give modest support for the hypothesis that TE insertions have greater average dominance in their viability effects than do point mutations, possibly as a result of deleterious effects of expression of TE-encoded genes.

Animals↗
PubMed2003

Multilocus models of sympatric speciation: Bush versus Rice versus Felsenstein.

In populations of phytophagous insects that use the host plant as a rendezvous for mating, divergence in host preference could lead to sympatric speciation. Speciation requires the elimination of "generalist" genotypes, that is, those with intermediate host preference. This could occur because such genotypes have an inherent fitness disadvantage, or because preference alleles become associated with alleles that are oppositely selected on the two hosts. Although the former mechanism has been shown to be plausible, the latter mechanism has not been studied in detail. I consider a multilocus model (the "Bush model") in which one set of biallelic loci affects host preference, and a second set affects viability on the hosts once chosen. Alleles that increase viability on one host decrease viability on the other, and all loci are assumed to be unlinked. With moderately strong selection on the viability loci, preference alleles rapidly become associated with viability alleles, and the population splits into two reproductively isolated host specialist populations. The conditions for speciation to occur in this model, as measured by the strength of selection required, are somewhat more stringent than in a model in which preference and viability are controlled by the same loci (one-trait model). In contrast, the conditions are much less stringent than in a model in which speciation requires buildup of associations between viability loci and loci controlling a host-independent assortative mating trait (canonical two-trait model). Moreover, in the one-trait model, and to a lesser extent the Bush model, the strength of selection needed to initiate speciation is only slightly greater than that needed to complete it. This indicates that documenting instances of sympatric species that are reproductively isolated only by host or habitat preference would provide evidence for the plausibility of sympatric speciation in nature.

Alleles↗
PubMed2002

Environment dependence of mutational parameters for viability in Drosophila melanogaster.

The genomic rate of mildly deleterious mutations (U) figures prominently in much evolutionary and ecological theory. In Drosophila melanogaster, estimates of U have varied widely, from <0.1 to nearly 1 per zygote. The source of this variation is unknown, but could include differences in the conditions used for assaying fitness traits. We examined how assay conditions affect estimates of the rates and effects of viability-depressing mutations in two sets of lines with accumulated spontaneous mutations on the second chromosome. In each set, the among-line variance in egg-to-adult viability was significantly greater when viability was assayed using a high parental density than when it was assayed using a low density. In contrast, the proportional decline in viability due to new mutations did not differ between densities. Two other manipulations, lowering the temperature and adding ethanol to the medium, had no significant effects on either the mean decline or among-line variance. Cross-environment genetic correlations in viability were generally close to one, implying that most mutations reduced viability in all environments. Using data from the low-density, lower-bound estimates of U approached the classic, high values of Mukai and Ohnishi; at the high density, U estimates were similar to recently reported low values. The difference in estimated mutation rates, taken at face value, would imply that many mutations affected fitness at low density but not at high density, but this is shown to be incompatible with the observed high cross-environment correlations. Possible reasons for this discrepancy are discussed. Regardless of the interpretation, the results show that assay conditions can have a large effect on estimates of mutational parameters for fitness traits.

Analysis of Variance↗