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Trudy F C Mackay

Publications and source records attributed to Trudy F C Mackay.

At least 19 recordsLinked to original sources
PubMed2006

High-resolution mapping of quantitative trait loci affecting increased life span in Drosophila melanogaster.

Limited life span and senescence are near-universal characteristics of eukaryotic organisms, controlled by many interacting quantitative trait loci (QTL) with individually small effects, whose expression is sensitive to the environment. Analyses of mutations in model organisms have shown that genes affecting stress resistance and metabolism affect life span across diverse taxa. However, there is considerable segregating variation for life span in nature, and relatively little is known about the genetic basis of this variation. Replicated lines of Drosophila that have evolved increased longevity as a correlated response to selection for postponed senescence are valuable resources for identifying QTL affecting naturally occurring variation in life span. Here, we used deficiency complementation mapping to identify at least 11 QTL on chromosome 3 that affect variation in life span between five old (O) lines selected for postponed senescence and their five base (B) population control lines. Most QTL were sex specific, and all but one affected multiple O lines. The latter observation is consistent with alleles at intermediate frequency in the base population contributing to the response to selection for postponed senescence. The QTL were mapped with high resolution and contained from 12 to 170 positional candidate genes.

Animals↗
PubMed2006

Phenotypic variation and natural selection at catsup, a pleiotropic quantitative trait gene in Drosophila.

Quantitative traits are shaped by networks of pleiotropic genes . To understand the mechanisms that maintain genetic variation for quantitative traits in natural populations and to predict responses to artificial and natural selection, we must evaluate pleiotropic effects of underlying quantitative trait genes and define functional allelic variation at the level of quantitative trait nucleotides (QTNs). Catecholamines up (Catsup), which encodes a negative regulator of tyrosine hydroxylase , the rate-limiting step in the synthesis of the neurotransmitter dopamine, is a pleiotropic quantitative trait gene in Drosophila melanogaster. We used association mapping to determine whether the same or different QTNs at Catsup are associated with naturally occurring variation in multiple quantitative traits. We sequenced 169 Catsup alleles from a single population and detected 33 polymorphisms with little linkage disequilibrium (LD). Different molecular polymorphisms in Catsup are independently associated with variation in longevity, locomotor behavior, and sensory bristle number. Most of these polymorphisms are potentially functional variants in protein coding regions, have large effects, and are not common. Thus, Catsup is a pleiotropic quantitative trait gene, but individual QTNs do not have pleiotropic effects. Molecular population genetic analyses of Catsup sequences are consistent with balancing selection maintaining multiple functional polymorphisms.

Animals↗
PubMed2006

The genetic basis of postzygotic reproductive isolation between Drosophila santomea and D. yakuba due to hybrid male sterility.

A major unresolved challenge of evolutionary biology is to determine the nature of the allelic variants of "speciation genes": those alleles whose interaction produces inviable or infertile interspecific hybrids but does not reduce fitness in pure species. Here we map quantitative trait loci (QTL) affecting fertility of male hybrids between D. yakuba and its recently discovered sibling species, D. santomea. We mapped three to four X chromosome QTL and two autosomal QTL with large effects on the reduced fertility of D. yakuba and D. santomea backcross males. We observed epistasis between the X-linked QTL and also between the X and autosomal QTL. The X chromosome had a disproportionately large effect on hybrid sterility in both reciprocal backcross hybrids. However, the genetics of hybrid sterility differ between D. yakuba and D. santomea backcross males, both in terms of the magnitude of main effects and in the epistatic interactions. The QTL affecting hybrid fertility did not colocalize with QTL affecting sexual isolation in this species pair, but did colocalize with QTL affecting the marked difference in pigmentation between D. yakuba and D. santomea. These results provide the basis for future high-resolution mapping and ultimately, molecular cloning, of the interacting genes that contribute to hybrid sterility.

Animals↗
PubMed2006

The genetic basis of prezygotic reproductive isolation between Drosophila santomea and D. yakuba due to mating preference.

Sexual isolating mechanisms that act before fertilization are often considered the most important genetic barriers leading to speciation in animals. While progress has been made toward understanding the genetic basis of the postzygotic isolating mechanisms of hybrid sterility and inviability, little is known about the genetic basis of prezygotic sexual isolation. Here, we map quantitative trait loci (QTL) contributing to prezygotic reproductive isolation between the sibling species Drosophila santomea and D. yakuba. We mapped at least three QTL affecting discrimination of D. santomea females against D. yakuba males: one X-linked and one autosomal QTL affected the likelihood of copulation, and a second X chromosome QTL affected copulation latency. Three autosomal QTL also affected mating success of D. yakuba males with D. santomea. No epistasis was detected between QTL affecting sexual isolation. The QTL do not overlap between males and females and are not disproportionately concentrated on the X chromosome. There was some overlap in map locations of QTL affecting sexual isolation between D. santomea and D. yakuba with QTL affecting sexual isolation between D. simulans and D. mauritiana and with QTL affecting differences in pigmentation between D. santomea and D. yakuba. Future high-resolution mapping and, ultimately, positional cloning, will reveal whether these traits do indeed have a common genetic basis.

Animals↗
PubMed2005

Quantitative trait loci with age-specific effects on fecundity in Drosophila melanogaster.

Life-history theory and evolutionary theories of aging assume the existence of alleles with age-specific effects on fitness. While various studies have documented age-related changes in the genetic contribution to variation in fitness components, we know very little about the underlying genetic architecture of such changes. We used a set of recombinant inbred lines to map and characterize the effects of quantitative trait loci (QTL) affecting fecundity of Drosophila melanogaster females at 1 and 4 weeks of age. We identified one QTL on the second chromosome and one or two QTL affecting fecundity on the third chromosome, but these QTL affected fecundity only at 1 week of age. There was more genetic variation for fecundity at 4 weeks of age than at 1 week of age and there was no genetic correlation between early and late-age fecundity. These results suggest that different loci contribute to the variation in fecundity as the organism ages. Our data provide support for the mutation accumulation theory of aging as applied to reproductive senescence. Comparing the results from this study with our previous work on life-span QTL, we also find evidence that antagonistic pleiotropy may contribute to the genetic basis of senescence in these lines as well.

Aging↗
PubMed2005

Quantitative trait loci affecting the difference in pigmentation between Drosophila yakuba and D. santomea.

Using quantitative trait locus (QTL) mapping, we studied the genetic basis of the difference in pigmentation between two sister species of Drosophila: Drosophila yakuba, which, like other members of the D. melanogaster subgroup, shows heavy black pigmentation on the abdomen of males and females, and D. santomea, an endemic to the African island of São Tomé, which has virtually no pigmentation. Here we mapped four QTL with large effects on this interspecific difference in pigmentation: two on the X chromosome and one each on the second and third chromosomes. The same four QTL were detected in male hybrids in the backcrosses to both D. santomea and D. yakuba and in the female D. yakuba backcross hybrids. All four QTL exhibited strong epistatic interactions in male backcross hybrids, but only one pair of QTL interacted in females from the backcross to D. yabuka. All QTL from each species affected pigmentation in the same direction, consistent with adaptive evolution driven by directional natural selection. The regions delimited by the QTL included many positional candidate loci in the pigmentation pathway, including genes affecting catecholamine biosynthesis, melanization of the cuticle, and many additional pleiotropic effects.

Animals↗
PubMed2005

Polygenic mutation in Drosophila melanogaster: Mapping spontaneous mutations affecting sensory bristle number.

Our ability to predict long-term responses to artificial and natural selection, and understand the mechanisms by which naturally occurring variation for quantitative traits is maintained, depends on detailed knowledge of the properties of spontaneous polygenic mutations, including the quantitative trait loci (QTL) at which mutations occur, mutation rates, and mutational effects. These parameters can be estimated by mapping QTL that cause divergence between mutation-accumulation lines that have been established from an inbred base population and selected for high and low trait values. Here, we have utilized quantitative complementation to deficiencies to map QTL at which spontaneous mutations affecting Drosophila abdominal and sternopleural bristle number have occurred in 11 replicate lines during 206 generations of divergent selection. Estimates of the numbers of mutations were consistent with diploid per-character mutation rates for bristle traits of 0.03. The ratio of the per-character mutation rate to total mutation rate (0.023) implies that >2% of the genome could affect just one bristle trait and that there must be extensive pleiotropy for quantitative phenotypes. The estimated mutational effects were not, however, additive and exhibited dependency on genetic background consistent with diminishing epistasis. However, these inferences must be tempered by the potential for epistatic interactions between spontaneous mutations and QTL affecting bristle number on the deficiency-bearing chromosomes, which could lead to overestimates in numbers of QTL and inaccurate inference of gene action.

Animals↗
PubMed2005

Genetics and genomics of Drosophila mating behavior.

The first steps of animal speciation are thought to be the development of sexual isolating mechanisms. In contrast to recent progress in understanding the genetic basis of postzygotic isolating mechanisms, little is known about the genetic architecture of sexual isolation. Here, we have subjected Drosophila melanogaster to 29 generations of replicated divergent artificial selection for mating speed. The phenotypic response to selection was highly asymmetrical in the direction of reduced mating speed, with estimates of realized heritability averaging 7%. The selection response was largely attributable to a reduction in female receptivity. We assessed the whole genome transcriptional response to selection for mating speed using Affymetrix GeneChips and a rigorous statistical analysis. Remarkably, >3,700 probe sets (21% of the array elements) exhibited a divergence in message levels between the Fast and Slow replicate lines. Genes with altered transcriptional abundance in response to selection fell into many different biological process and molecular function Gene Ontology categories, indicating substantial pleiotropy for this complex behavior. Future functional studies are necessary to test the extent to which transcript profiling of divergent selection lines accurately predicts genes that directly affect the selected trait.

Animals↗
PubMed2005

Quantitative genomics of starvation stress resistance in Drosophila.

BACKGROUND: A major challenge of modern biology is to understand the networks of interacting genes regulating complex traits, and the subset of these genes that affect naturally occurring quantitative genetic variation. Previously, we used P-element mutagenesis and quantitative trait locus (QTL) mapping in Drosophila to identify candidate genes affecting resistance to starvation stress, and variation in resistance to starvation stress between the Oregon-R (Ore) and 2b strains. Here, we tested the efficacy of whole-genome transcriptional profiling for identifying genes affecting starvation stress resistance. RESULTS: We evaluated whole-genome transcript abundance for males and females of Ore, 2b, and four recombinant inbred lines derived from them, under control and starved conditions. There were significant differences in transcript abundance between the sexes for nearly 50% of the genome, while the transcriptional response to starvation stress involved approximately 25% of the genome. Nearly 50% of P-element insertions in 160 genes with altered transcript abundance during starvation stress had mutational effects on starvation tolerance. Approximately 5% of the genome exhibited genetic variation in transcript abundance, which was largely attributable to regulation by unlinked genes. Genes exhibiting variation in transcript abundance among lines did not cluster within starvation resistance QTLs, and none of the candidate genes affecting variation in starvation resistance between Ore and 2b exhibited significant differences in transcript abundance between lines. CONCLUSIONS: Expression profiling is a powerful method for identifying networks of pleiotropic genes regulating complex traits, but the relationship between variation in transcript abundance among lines used to map QTLs and genes affecting variation in quantitative traits is complicated.

Adaptation, Physiological↗
PubMed2005

Pinocchio, a novel protein expressed in the antenna, contributes to olfactory behavior in Drosophila melanogaster.

Most organisms depend on chemoreception for survival and reproduction. In Drosophila melanogaster multigene families of chemosensory receptors and putative odorant binding proteins have been identified. Here, we introduce an additional distinct protein, encoded by the CG4710 gene, that contributes to olfactory behavior. Previously, we identified through P[lArB]-element mutagenesis a smell impaired (smi) mutant, smi21F, with odorant-specific defects in avoidance responses. Here, we show that the smi21F mutant also exhibits reduced attractant responses to some, but not all, of a select group of odorants. Furthermore, electroantennogram amplitudes are increased in smi21F flies. Characterization of flanking sequences of the P[lArB] insertion site, complementation mapping, phenotypic reversion through P-element excision, and expression analysis implicate a predicted gene, CG4710, as the candidate smi gene. CG4710 produces two transcripts that encode proteins that contain conserved cysteines and which are reduced in the smi21F mutant. Furthermore, in situ hybridization reveals CG4710 expression in the third antennal segment. We have named this gene of previously unknown function and its product "Pinocchio (Pino)".

Amino Acid Sequence↗
PubMed2005

Microclinal variation for ovariole number and body size in Drosophila melanogaster in 'Evolution Canyon'.

Sites that display strong environmental contrasts in close proximity, such as 'Evolution Canyon' on Mt. Carmel, Israel, are natural theatres for investigating adaptive evolution in action. We reared Drosophila melanogaster from collection sites along altitudinal transects on the north- and south-facing canyon slopes in each of three temperature environments, and assessed genetic variation in ovariole number and body size between and within collection sites, and temperature plasticity. Both traits exhibited significant genetic variation within collection sites and phenotypic plasticity in response to temperature, but not genetic variation for plasticity. Between-site genetic variation in ovariole number was negatively correlated with altitude on both slopes of the canyon, and collections from the north- and south-facing slopes were genetically differentiated for male, but not female, body size. Genetic variation between sites within easy dispersal range is consistent with the action of strong natural selection, although neither the selective agent(s) nor the direct targets of selection are known.

Adaptation, Biological↗
PubMed2004

Methods for genetic dissection of complex traits.

In this Perspective, the author responds to a recent SAGE KE Perspective. An alternative view of the benefits of quantitative trait loci mapping as a way to understand the molecular mechanisms of life-span determination is presented.

Animals↗
PubMed2004

The genetic architecture of quantitative traits: lessons from Drosophila.

Understanding the genetic architecture of quantitative traits begins with identifying the genes regulating these traits, mapping the subset of genetically varying quantitative trait loci (QTLs) in natural populations, and pinpointing the molecular polymorphisms defining QTL alleles. Studies in Drosophila have revealed large numbers of pleiotropic genes that interact epistatically to regulate quantitative traits, and large numbers of QTLs with sex-, environment- and genotype-specific effects. Multiple molecular polymorphisms in regulatory regions of candidate genes are often associated with variation for complex traits. These observations offer valuable lessons for understanding the genetic basis of variation for complex traits in other organisms, including humans.

Animals↗
PubMed2004

Quantitative trait loci affecting natural variation in Drosophila longevity.

Limited life span and senescence are universal phenomena, controlled by genetic and environmental factors whose interactions both limit life span and generate variation in life span between individuals, populations and species. To understand the genetic architecture of longevity it is necessary to know what loci affect variation in life span, what are the allelic effects at these loci and what molecular polymorphisms define quantitative trait locus (QTL) alleles. Here, we used quantitative complementation tests to determine whether genes that regulate longevity also contribute to naturally occurring variation in Drosophila life span. Inbred strains derived from a natural population were crossed to stocks containing null mutations (m) or deficiencies (Df) uncovering the candidate genes, maintained over a Balancer (Bal) chromosome. We measured the life span of the resulting F(1) genotypes, +(i)/m (Df) and +(i)/Bal, where +(i) denotes one of the i natural alleles. Failure of the QTL alleles to complement the candidate gene mutation is indicated by a significant cross (mutant versus wild-type allele of the candidate gene) by inbred line interaction term from analysis of variance of life span. Failure to complement indicates a genetic interaction between the candidate gene allele and the naturally occurring life span QTL, and implicates the candidate gene as potential cause of variation in longevity. Of the 16 candidate regions and genes tested, Df(2L)c17, Df(3L)Ly, Df(3L)AC1 and Df(3R)e-BS2 showed significant failure to complement wild-type alleles in both sexes, and an Alcohol dehydrogenase mutant failed to complement in females. Several genes that regulate life span (e.g., Superoxide dismutase, Catalase, and rosy) complemented the life span effects of wild-derived alleles, suggesting little natural variation affecting longevity at these loci, at least in this sample of alleles. Quantitative complementation tests are therefore useful for identifying QTL contributing to segregating genetic variation in life span in nature.

Aging↗
PubMed2004

Quantitative genetic analyses of complex behaviours in Drosophila.

Behaviours are exceptionally complex quantitative traits. Sensitivity to environmental variation and genetic background, the presence of sexual dimorphism, and the widespread functional pleiotropy that is inherent in behavioural phenotypes pose daunting challenges for unravelling their underlying genetics. Drosophila melanogaster provides an attractive system for elucidating the unifying principles of the genetic architectures that drive behaviours, as genetically identical individuals can be reared rapidly in controlled environments and extensive publicly accessible genetic resources are available. Recent advances in quantitative genetic and functional genomic approaches now enable the extensive characterization of complex genetic networks that mediate behaviours in this important model organism.

Animals↗
PubMed2004

Shuttle craft: a candidate quantitative trait gene for Drosophila lifespan.

Variation in longevity in natural populations is attributable to the segregation of multiple interacting loci, whose effects are sensitive to the environment. Although there has been considerable recent progress towards understanding the environmental factors and genetic pathways that regulate lifespan, little is known about the genes causing naturally occurring variation in longevity. Previously, we used deficiency complementation mapping to map two closely linked quantitative trait loci (QTL) causing female-specific variation in longevity between the Oregon (Ore) and 2b strains of Drosophila melanogaster to 35B9-C3 and 35C3 on the second chromosome. The 35B9-C3 QTL encompasses a 50-kb region including four genes, for one of which, shuttle craft (stc), mutations have been generated. The 35C3 QTL localizes to a 200-kb interval with 15 genes, including three genes for which mutations exist (reduced (rd), guftagu (gft) and ms(2)35Ci). Here, we report quantitative complementation tests to mutations at these four positional candidate genes, and show that ms(2)35Ci and stc are novel candidate quantitative trait genes affecting variation in Drosophila longevity. Complementation tests with stc alleles reveal sex- and allele-specific failure to complement, and complementation effects are dependent on the genetic background, indicating considerable epistasis for lifespan. In addition, a homozygous viable stc allele has a sex-specific effect on lifespan. stc encodes an RNA polymerase II transcription factor, and is an attractive candidate gene for the regulation of longevity and variation in longevity, because it is required for motoneuron development and is expressed throughout development. Quantitative genetic analysis of naturally occurring variants with subtle effects on lifespan can identify novel candidate genes and pathways important in the regulation of longevity.

Aging↗