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M L Wayne

Publications and source records attributed to M L Wayne.

10 recordsLinked to original sources
PubMed2005

Genetic architecture of two fitness-related traits in Drosophila melanogaster: ovariole number and thorax length.

In Drosophila melanogaster, ovariole number and thorax length are morphological characters thought to be associated with fitness. Maximum daily egg production in females is positively correlated with ovariole number, while thorax length is correlated with male reproductive success and female fecundity. Though both traits are related to fitness, ovariole number is likely to be under stabilizing selection, while thorax length appears to be under directional selection. Current research has focused on examining the sources of variation for ovariole number in relation to fitness, with a view towards elucidating how segregating variation is maintained in natural populations. Here, we utilize a diallel design to explore the genetic architecture of ovariole number and thorax length in nine isogenic lines derived from a natural population. The full diallel design allows the estimation of general combining ability (GCA), specific combining ability (SCA), and also describes variation due to reciprocal effects (RGCA and RSCA). Ovariole number and thorax length differed with respect to their genetic architecture, reflective of the independent selective forces acting on the traits. For ovariole number, GCA accounted for the majority (67.3%) of variation segregating between the lines, with no evidence of reciprocal effects or inbreeding depression; SCA accounted for a small percentage (3.9%) of the variance, suggesting dominance variation; no reciprocal effects were observed. In contrast, for thorax length, the majority of the non-error variance was accounted for by SCA (17.9%), with only one third as much variance (6.2%) due to GCA. Interestingly, RSCA (nuclear-extranuclear interactions) accounted for slightly more variation (7.5%) than GCA in these data. Thus, genetic variation for thorax length is largely in accord with predictions for a fitness trait under directional selection: little additive genetic variation and substantial dominance variation (including a suggestion of inbreeding depression); while the mechanisms underlying the maintenance of variation for ovariole number are more complex.

Animals↗
PubMed2004

Additivity and trans-acting effects on gene expression in male Drosophila simulans.

Understanding how genetic variation is maintained begins with a comprehensive description of what types of genetic variation exist, the extent and magnitude of the variation, and patterns discernable in that variation. However, such studies have focused primarily on DNA sequence data and have ignored genetic variation at other hierarchical levels of genetic information. Microarray technology permits an examination of genetic variation at the level of mRNA abundance. Utilizing a round-robin design, we present a quantitative description of variation in mRNA abundance in terms of GCA (general combining ability or additive variance). We test whether genes significant for GCA are randomly distributed across chromosomes and use a nonparametric approach to demonstrate that the magnitude of the variation is not random for GCA. We find that there is a paucity of genes significant for GCA on the X relative to the autosomes. The overall magnitude of the effects for GCA on the X tends to be lower than that on the autosomes and is contributed by rare alleles of larger effect. Due to male hemizygosity, GCA for X-linked phenotypes must be due to trans-acting factors, while GCA for autosomal phenotypes may be due to cis- or trans-acting factors. The contrast in the amount of variation between the X and the autosomes suggests that both cis and trans factors contribute to variation for expression in D. simulans with the preponderance of effects being trans. This nonrandom patterning of genetic variation in gene expression data with respect to chromosomal context may be due to hemizygosity in the male.

Animals↗
PubMed2002

Combining mapping and arraying: An approach to candidate gene identification.

A combination of quantitative trait locus (QTL) mapping and microarray analysis was developed and used to identify 34 candidate genes for ovariole number, a quantitative trait, in Drosophila melanogaster. Ovariole number is related to evolutionary fitness, which has been extensively studied, but for which few a priori candidate genes exist. A set of recombinant inbred lines were assayed for ovariole number, and QTL analyses for this trait identified 5,286 positional candidate loci. Forty deletions spanning the QTL were employed to further refine the map position of genes contributing to variation in this trait between parental lines, with six deficiencies showing significant effects and reducing the number of positional candidates to 548. Parental lines were then assayed for expression differences by using Affymetrix microarray technology, and ANOVA was used to identify differentially expressed genes in these deletions. Thirty-four genes were identified that showed evidence for differential expression between the parental lines, one of which was significant even after a conservative Bonferroni correction. The list of potential candidates includes 5 genes for which previous annotations did not exist, and therefore would have been unlikely choices for follow-up from mapping studies alone. The use of microarray technology in this context allows an efficient, objective, quantitative evaluation of genes in the QTL and has the potential to reduce the overall effort needed in identifying genes causally associated with quantitative traits of interest.

Analysis of Variance↗
PubMed2001

Quantitative trait locus mapping of fitness-related traits in Drosophila melanogaster.

We examined the genetic architecture of four fitness-related traits (reproductive success, ovariole number, body size and early fecundity) in a panel of 98 Oregon-R x 2b3 recombinant inbred lines (RILs). Highly significant genetic variation was observed in this population for female, but not male, reproductive success. The cross-sex genetic correlation for reproductive success was 0.20, which is not significantly different from zero. There was significant genetic variation segregating in this cross for ovariole number, but not for body size or early fecundity. The RILs were genotyped for cytological insertion sites of roo transposable elements, yielding 76 informative markers with an average spacing of 3.2 cM. Quantitative trait loci (QTL) affecting female reproductive success and ovariole number were mapped using a composite interval mapping procedure. QTL for female reproductive success were located at the tip of the X chromosome between markers at cytological locations 1B and 3E; and on the left arm of chromosome 2 in the 30D-38A cytological region. Ovariole number QTL mapped to cytological intervals 62D-69D and 98A-98E, both on the third chromosome. The regions harbouring QTL for female reproductive success and ovariole number were also identified as QTL for longevity in previous studies with these lines.

Analysis of Variance↗
PubMed1998

Quantitative genetics of ovariole number in Drosophila melanogaster. II. Mutational variation and genotype-environment interaction.

The rare alleles model of mutation-selection balance (MSB) hypothesis for the maintenance of genetic variation was evaluated for two quantitative traits, ovariole number and body size. Mutational variances (VM) for these traits, estimated from mutation accumulation lines, were 4.75 and 1.97 x 10(-4) times the environmental variance (VE), respectively. The mutation accumulation lines were studied in three environments to test for genotype x environment interaction (GEI) of new mutations; significant mutational GEI was found for both traits. Mutations for ovariole number have a quadratic relationship with competitive fitness, suggesting stabilizing selection for the trait; there is no significant correlation between mutations for body size and competitive fitness. Under MSB, the ratio of segregating genetic variance, VG, to mutational variance, VM, estimates the inverse of the selection coefficient against a heterozygote for a new mutation. Estimates of VG/VM for ovariole number and body size were both approximately 1.1 x 10(4). Thus, MSB can explain the level of variation, if mutations affecting these traits are under very weak selection, which is inconsistent with the empirical observation of stabilizing selection, or if the estimate of VM is biased downward by two orders of magnitude. GEI is a possible alternative explanation.

Analysis of Variance↗
PubMed1996

Reduced variation at concertina, a heterochromatic locus in Drosophila.

In Drosophila melanogaster and closely related species, polymorphism has been shown to be reduced at loci located in regions of low recombination on the X chromosome and on the fourth chromosome, which does not normally recombine. This positive correlation between nucleotide polymorphism level and recombination rate is not predicted by standard neutral theory and therefore must result from natural selection and genetic hitchhiking along the chromosomes. We report here the near-complete absence of variation at concertina (cta), a locus located in the beta-heterochromatic base of chromosome 2L, a region of strongly reduced recombination. A 1.2 kilobase region containing coding regions and introns was sequenced from each of nine lines of D. melanogaster and nine lines of D. simulans representing worldwide collections. Variation is significantly reduced in eta in both species compared with other available loci on the same chromosome. Two analyses of background selection demonstrate that the reduction in variation at cta. considered in combination with other loci on chromosome 2L or alone, is consistent with the background selection model.

Animals↗
PubMed1996

Quantitative genetic variation of odor-guided behavior in a natural population of Drosophila melanogaster.

Quantitative genetic variation in behavioral response to the odorant, benzaldehyde, was assessed among a sample of 43 X and 35 third chromosomes extracted from a natural population and substituted into a common inbred background. Significant genetic variation among chromosome lines was detected. Heritability estimates for olfactory response, however, were low, as is typical for traits under natural selection. Furthermore, the loci affecting naturally occurring variation in olfactory response to benzaldehyde were not the same in males and females, since the genetic correlation between the sexes was low and not significantly different from zero for the chromosome 3 lines. Competitive fitness, viability and fertility of the chromosome 3 lines were estimated using the balancer equilibrium technique. Genetic correlations between fitness and odor-guided behavior were not significantly different from zero, suggesting the number of loci causing variation in olfactory response is small relative to the number of loci causing variation in fitness. Since different genes affect variation in olfactory response in males and females, genetic variation for olfactory response could be maintained by genotype x sex environment interaction. This unusual genetic architecture implies that divergent evolutionary trajectories for olfactory behavior may occur in males and females.

Animals↗
PubMed1996

Molecular population genetics of ref(2)P, a locus which confers viral resistance in Drosophila.

The ref(2)P locus (2-54.2) is polymorphic for two allelic forms in natural populations of Drosophila melanogaster, ref(2)Po and ref(2)Pp. The latter allele confers resistance to the rhabdovirus sigma infecting wild populations. Previous work, based on a small sample of prescreened restrictive (resistant) and permissive (susceptible) alleles, identified a large number of amino acid replacement changes (7) relative to synonymous changes (1). Such protein variability could be the result of variation-enhancing selection. To further test the selection hypothesis, we have examined the DNA sequences of ten randomly chosen lines of D. melanogaster and one line of D. simulans. Nine of the ten lines are permissive; D. simulans does not harbor the virus. The melanogaster alleles contain 4 synonymous changes, 19 noncoding changes, and 13 amino acid replacement changes, indicating a relatively high level of polymorphism. Three sequenced restrictive alleles have nearly identical sequences, indicating that they are relatively young. Compared to the permissive alleles, they share only a complex deletion at codon 34, CAG-AAT to GGA, which our analysis indicates to be the site conferring the restrictive phenotype. Patterns of polymorphism and divergence differ from neutral predictions by several criteria for the amino terminal region, which contains the complex deletion (codons 1-91), but not the remainder of the protein (codons 92-599). We find a higher rate of evolution on the D. melanogaster lineage than on the D. simulans lineage. The relatively large amount of both replacement and silent polymorphism in the permissive alleles and the lack of divergence between permissive and restrictive alleles suggests that the sigma virus and ref(2)P may be engaged in an evolutionary race in which new restrictive alleles are continually arising but are relatively short-lived.

Alleles↗
PubMed1989

Effect of the bile-acid sequestrant colestipol on postprandial serum bile-acid concentration: evaluation by bioluminescent enzymic analysis.

Chronic ingestion of bile-acid sequestrants has been shown to decrease the serum cholesterol concentration and coronary events in hypercholesterolaemic patients. To develop improved sequestrants, a rapid, convenient method for testing the bile-acid binding efficacy of sequestrants is needed. Serum bile-acid concentrations could be used to detect bile-acid binding by an administered sequestrant, since the serum bile-acid concentration is determined largely by the rate of intestinal absorption in healthy individuals. To test this, serum bile-acid concentrations were measured at frequent intervals over 24 h in five otherwise healthy hypercholesterolaemic subjects during the ingestion of three standard meals, with or without the addition of 5 g colestipol granules administered 30 min before each meal. Total serum bile-acid concentration was measured with a previously reported bioluminescent enzymic assay, that uses a 3 alpha-hydroxysteroid dehydrogenase, an oxido-reductase, and a bacterial luciferase co-immobilized on to Sepharose beads. Bile acids in 1 ml of serum were isolated by solid-phase extraction chromatography with reversed-phase C18 cartridges. Colestipol lowered the postprandial elevation of serum bile acids by one half, with a subsequent decrease in the cumulative area under the curve. The data suggest that measurement of serum bile-acid concentrations by bioluminescence is a rapid, simple way to document the efficacy of bile-acid sequestrants.

Adolescent↗