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T F Mackay

Publications and source records attributed to T F Mackay.

52 records · Page 3Linked to original sources
PubMed1995

Polygenic mutation in Drosophila melanogaster: the causal relationship of bristle number to fitness.

The association between sternopleural and abdominal bristle number and fitness in Drosophila melanogaster was determined for sublines of an initially highly inbred strain that were maintained by divergent artificial selection for 150 generations or by random mating for 180 generations. Replicate selection lines had more extreme bristle numbers than those that were maintained without artificial selection at the same census size for approximately the same number of generations. The average fitness, estimated by a single generation of competition against a compound autosome strain, was 0.17 for lines selected for high and low abdominal bristle numbers and 0.19 for lines selected for high and low sternopleural bristle number. The average fitness of unselected lines, 0.46, was significantly higher than that of the selection lines. The fitnesses and the relationships of bristle number to fitness in progeny of all possible crosses of high x high (H x H), high x low (H x L) and low x low (L x L) selection lines were examined to determine whether the observed intermediate optima were caused by direct stabilizing selection on bristle number or by apparent stabilizing selection mediated through deleterious pleiotropic fitness effects of mutations affecting bristle number. Although bristle number was nearly additive for progeny of H x H, H x L and L x L crosses among sternopleural bristle selection lines, their mean fitnesses were not significantly different from each other, or from the mean fitness of the unselected lines, suggesting partly or completely recessive pleiotropic fitness effects cause apparent stabilizing selection. The average fitness of the progeny of H x H abdominal bristle selection lines was not significantly different from the fitness of unselected lines, but the mean fitness of the progeny of L x L crosses was not significantly different from that of the pure low lines. This is consistent with direct selection against low but not high abdominal bristle number, but the interpretation is confounded by variation in average degree of dominance for fitness (on average recessive in the high abdominal bristle selection lines and additive in the low abdominal bristle selection lines). Neither direct stabilizing selection nor pleiotropy, therefore, can account for all the observations.

Animals↗
PubMed1995

High resolution mapping of genetic factors affecting abdominal bristle number in Drosophila melanogaster.

Factors responsible for selection response for abdominal bristle number and correlated responses in sternopleural bristle number were mapped to the X and third chromosome of Drosophila melanogaster. Lines divergent for high and low abdominal bristle number were created by 25 generations of artificial selection from a large base population, with an intensity of 25 individuals of each sex selected from 100 individuals of each sex scored per generation. Isogenic chromosome substitution lines in which the high (H) X or third chromosome were placed in an isogenic low (L) background were derived from the selection lines and from the 93 recombinant isogenic (RI) HL X and 67 RI chromosome 3 lines constructed from them. Highly polymorphic neutral roo transposable elements were hybridized in situ to the polytene chromosomes of the RI lines to create a set of cytogenetic markers. These techniques yielded a dense map with an average spacing of 4 cM between informative markers. Factors affecting bristle number, and relative viability of the chromosome 3 RI lines, were mapped using a multiple regression interval mapping approach, conditioning on all markers > or = 10 cM from the tested interval. Two factors with large effects on abdominal bristle number were mapped on the X chromosome and five factors on the third chromosome. One factor with a large effect on sternopleural bristle number was mapped to the X and two were mapped to the third chromosome; all factors with sternopleural effects corresponded to those with effects on abdominal bristle number. Two of the chromosome 3 factors with large effects on abdominal bristle number were also associated with reduced viability. Significant sex-specific effects and epistatic interactions between mapped factors of the same order of magnitude as the additive effects were observed. All factors mapped to the approximate positions of likely candidate loci (ASC, bb, emc, h, mab, Dl and E(spl), previously characterized by mutations with large effects on bristle number.

Abdomen↗
PubMed1995

Polygenic mutation in Drosophila melanogaster: genetic analysis of selection lines.

We have conducted genetic analyses of 12 long-term selection lines of Drosophila melanogaster derived from a highly inbred base population, containing new mutations affecting abdominal and sternopleural bristle number. Biometric analysis of the number of effective factors differentiating the selected lines from the base inbred indicated that with the exception of the three lines selected for increased number of abdominal bristles, three or more mutations contributed to the responses of the selection lines. Analysis of the chromosomal distribution of effects revealed that mutations affecting abdominal bristle number occurred on all three major chromosomes. In addition, Y-linked mutations with effects ranging from one to three bristles occurred in all three lines selected for decreased number of abdominal bristles, as well as in one line selected for increased abdominal bristle number. Mutations affecting sternopleural bristle number were mainly on the X and third chromosomes. One abdominal and one sternopleural selection line showed evidence of a segregating lethal with large effects on bristle number. As an indirect test for allelism of mutations occurring in different selection lines, the three lines selected in the same direction for the same trait were crossed in all possible combinations, and selection continued from the F2 hybrids. Responses of the hybrid lines usually did not exceed those of the most extreme parental lines, indicating that the responses of the parental lines may have been partly due to mutations at the same loci, although other interpretations are possible.

Abdomen↗
PubMed1994

Naturally occurring variation in bristle number and DNA polymorphisms at the scabrous locus of Drosophila melanogaster.

The association between quantitative genetic variation in bristle number and molecular variation at a candidate neurogenic locus, scabrous, was examined in Drosophila melanogaster. Approximately 32 percent of the genetic variation in abdominal bristle number (21 percent for sternopleural bristle number) among 47 second chromosomes from a natural population was correlated with DNA sequence polymorphisms at this locus. Several polymorphic sites associated with large phenotypic effects occurred at intermediate frequency. Quantitative genetic variation in natural populations caused by alleles that have large effects at a few loci and that segregate at intermediate frequencies conflicts with the classical infinitesimal model of the genetic basis of quantitative variation.

Alleles↗
PubMed1994

Direct determination of retrotransposon transposition rates in Drosophila melanogaster.

Rates of transposition and excision of the Drosophila melanogaster retrotransposon elements mdg3, 297, Doc, roo and copia were estimated directly, by in situ hybridization analysis of their cytological insertion sites in 31 replicates of a highly inbred line that had accumulated spontaneous mutations for approximately 160 generations. Estimated transposition rates of Doc, roo and copia were, respectively, 4.2 x 10(-5), 3.1 x 10(-4) and 1.3 x 10(-3); no transpositions of 297 nor mdg3 were observed. Rates of transposition of copia varied significantly among sublines. Excisions were only observed for roo elements, at a rate of 9.0 x 10(-6) per element per generation. Copy number averaged over these element families increased 5.9%; therefore, in these lines the magnitude of the forces opposing transposable element multiplication were weaker than transposition rates. Estimated total genomic mutation rates from transposition are of the same order as the nucleotide mutation rate in this species.

Animals↗
PubMed1994

Polygenic mutation in Drosophila melanogaster: estimates from response to selection of inbred strains.

Replicated divergent artificial selection for abdominal and sternopleural bristle number from a highly inbred strain of Drosophila melanogaster resulted in an average divergence after 125 generations of selection of 12.0 abdominal and 8.2 sternopleural bristles from the accumulation of new mutations affecting bristle number. Responses to selection were highly asymmetrical, with greater responses for low abdominal and high sternopleural bristle numbers. Estimates of VM, the mutational variance arising per generation, based on the infinitesimal model and averaged over the responses to the first 25 generations of selection, were 4.32 x 10(-3) VE for abdominal bristle number and 3.66 x 10(-3) VE for sternopleural bristle number, where VE is the environmental variance. Based on 10 generations of divergent selection within lines from generation 93, VM for abdominal bristle number was 6.75 x 10(-3) VE and for sternopleural bristle number was 5.31 x 10(-3) VE. However, estimates of VM using the entire 125 generations of response to selection were lower and generally did not fit the infinitesimal model largely because the observed decelerating responses were not compatible with the predicted increasing genetic variance over time. These decelerating responses, periods of response in the opposite direction to artificial selection, and rapid responses to reverse selection all suggest new mutations affecting bristle number on average have deleterious effects on fitness. Commonly observed periods of accelerated responses followed by long periods of stasis suggest a leptokurtic distribution of mutational effects for bristles.

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PubMed1993

Accounting for bias in estimates of the rate of polygenic mutation.

Experimental data on the rate of response to artificial selection in initially inbred lines or the rate of divergence among inbred sublines can be used to estimate the rate of increase in variance of quantitative traits from new mutations. So far estimates have been based on the infinitesimal model of many genes with small additive effects which imply a rate of increase in heritability for Drosophila melanogaster bristle number traits of about 0.1% per generation. Such estimates are biased because mutants tend to have large effects, to have non-additive gene action, and to be deleterious. Here, recent information on the distribution of effects of new mutations on Drosophila melanogaster bristle number and viability is used to infer the direction and magnitude of this bias. The infinitesimal model tends to underestimate the mutational variance, typically by a factor of about 3, but this factor depends on the experimental design. Averages of revised estimates, accounting for this bias, of the per generation increment in heritability from mutation are 0.36% and 0.21% for abdominal and sternopleural bristle number, respectively, in experiments involving M strains, and 1.4% and 0.7% for abdominals and sternopleurals, respectively, in P strains.

Animals↗
PubMed1993

Mapping and characterization of P-element-induced mutations at quantitative trait loci in Drosophila melanogaster.

X chromosomes derived from crosses of inbred P and M Drosophila melanogaster strains that had extreme effects on abdominal and/or sternopleural bristle number in males, were further analyzed to determine their effects in females and to map the loci at which the mutations occurred. Seven lines that had on average 3.9 fewer sternopleural bristles than wildtype in males had average homozygous sternopleural bristle effects of -2.2. The bristle effects were partially recessive, with an average degree of dominance of -0.60. Physical mapping of the sternopleural bristle effects of these lines placed them all at approximately 24.7 cM. These mutations are apparently allelic on the basis of a complementation test, and deficiency mapping indicates they occur within chromosomal bands 8A4; 8C6. In situ hybridization analysis of the sites of P element insertions of these lines suggests that mutations probably resulted from excision of P elements at 8C on the original inbred P strain chromosome. Two additional lines, NDC(19) and DP(146), had reduced numbers of sternopleural and abdominal bristles. NDC(19) males had 9.7 fewer abdominal and 8.6 fewer sternopleural bristles than wildtype. The corresponding homozygous abdominal and sternopleural bristle number effects were -5.8 and -3.8, respectively; with the abdominal bristle effect completely recessive and the sternopleural bristle effect nearly additive. DP(146) males had 6.2 fewer abdominal and 4.1 fewer sternopleural bristles than wildtype, with homozygous abdominal bristle effects of -4.3 and sternopleural bristle effects of -2.0. Abdominal bristle effects of this line were partially recessive whereas the sternopleural bristle effects were additive. Physical mapping showed effects on both bristle traits segregated jointly in these two lines, with the NDC(19) mutation closely linked to y and the DP(146) mutation 0.17 cM from it. Complementation tests and deficiency mapping also indicate the mutations in lines NDC(19) and DP(146) are at closely linked but separate loci within chromosomal bands 1B2; 1B4-6 and 1B4-6; 1B10 respectively, with some epistatic effects. In situ hybridization analysis of sites of P element insertion suggest that the NDC(19) mutation, which may be a scute allele, was probably caused by a P element insertion in the 1B region; the DP(146) mutation is also associated with an insertion at 1B.

Animals↗
PubMed1992

Effects of P element insertions on quantitative traits in Drosophila melanogaster.

P element mutagenesis was used to construct 94 third chromosome lines of Drosophila melanogaster which contained on average 3.1 stable P element inserts, in an inbred host strain background previously free of P elements. The homozygous and heterozygous effects of the inserts on viability and abdominal and sternopleural bristle number were ascertained by comparing the chromosome lines with inserts to insert-free control lines of the inbred host strain. P elements reduced average homozygous viability by 12.2% per insert and average heterozygous viability by 5.5% per insert, and induced recessive lethal mutations at a rate of 3.8% per insert. Mutational variation for the bristle traits averaged over both sexes was 0.03Ve per homozygous P insert and 0.003Ve per heterozygous P insert, where Ve is the environmental variance. Mutational variation was greater for the sexes considered separately because inserts had large pleiotropic effects on sex dimorphism of bristle characters. The distributions of homozygous effects of inserts on the bristle traits were asymmetrical, with the largest effects in the direction of reducing bristle number; and highly leptokurtic, with most of the increase in variance contributed by a few lines with large effects. The inserts had partially recessive effects on the bristle traits. Insert lines with extreme bristle effects had on average greatly reduced viability.

Animals↗
PubMed1990

Molecular and phenotypic variation in the achaete-scute region of Drosophila melanogaster.

Variation in quantitative characters underlies much adaptive evolution and provides the basis for selective improvement of domestic species, yet the genetic nature of quantitative variation is poorly understood. Many loci affecting quantitative traits have been identified by the segregation of mutant alleles with major qualitative effects. These alleles may represent an extreme of a continuum of allelic effects, and most quantitative variation could result from the segregation of alleles with subtle effects at loci identified by alleles with major effects. The achaete-scute complex in Drosophila melanogaster plays a central part in bristle development and has been characterized at the molecular level. The hypothesis that naturally occurring quantitative variation in bristle number could be associated with wild-type alleles of achaete-scute was tested by correlating phenotypic variation in bristle number with molecular variation in restriction maps in this region among chromosomes extracted from natural populations. DNA insertion variation in the achaete-scute region was found to be strongly associated with variation in bristle number.

Alleles↗
PubMed1990

Hybrid dysgenesis-induced quantitative variation on the X chromosome of Drosophila melanogaster.

To determine the ability of the P-M hybrid dysgenesis system of Drosophila melanogaster to generate mutations affecting quantitative traits, X chromosome lines were constructed in which replicates of isogenic M and P strain X chromosomes were exposed to a dysgenic cross, a nondysgenic cross, or a control cross, and recovered in common autosomal backgrounds. Mutational heritabilities of abdominal and sternopleural bristle score were in general exceptionally high-of the same magnitude as heritabilities of these traits in natural populations. P strain chromosomes were eight times more mutable than M strain chromosomes, and dysgenic crosses three times more effective than nondysgenic crosses in inducing polygenic variation. However, mutational heritabilities of the bristle traits were appreciable for P strain chromosomes passed through one nondysgenic cross, and for M strain chromosomes backcrossed for seven generations to inbred P strain females, a result consistent with previous observations on mutations affecting quantitative traits arising from nondysgenic crosses. The new variation resulting from one generation of mutagenesis was caused by a few lines with large effects on bristle score, and all mutations reduced bristle number.

Animals↗
PubMed1990

Transposable element-induced response to artificial selection in Drosophila melanogaster: molecular analysis of selection lines.

Artificial selection lines for abdominal bristle score of Drosophila melanogaster established from P-M hybrid dysgenic crosses showed increases in selection response, heritability and phenotypic variance compared to similar lines started from nondysgenic crosses. To determine whether this increased genetic variance could be due to enhanced transposition of P elements following the dysgenic cross, the cytological locations (sites) of P elements were determined by in situ hybridization for the whole genome of samples of 20 individuals from the parental P strain, 20 individuals from each of the eight dysgenic selection lines, and ten individuals from each of the eight nondysgenic selection lines. Variation among and within the selection lines and the parental P strain in P element insertion sites was exceptionally high. A total of 601 sites were identified, but there was no difference in total number of sites per line, mean number of sites per individual, mean copy number per individual, or site frequency between dysgenic and nondysgenic selection lines, or between lines selected for high and low bristle score. Transposition following nondysgenic crosses may explain additional observations of accelerated selection responses in nondysgenic selection lines. It was not possible to deduce which, if any, of the several hundred insertions in the dysgenic selection lines were responsible for their extreme bristle phenotypes.

Animals↗
PubMed1989

Hybrid dysgenesis-induced response to selection in Drosophila melanogaster.

In Drosophila melanogaster, the P-M and I-R systems of hybrid dysgenesis are associated with high rates of transposition of P and I elements, respectively, in the germlines of dysgenic hybrids formed by crossing females of strains without active elements to males of strains containing them. Transposition rates are not markedly accelerated in the reciprocal, nondysgenic hybrids. Previous attempts to evaluate the extent to which hybrid dysgenesis-mediated P transposition contributes to mutational variance for quantitative characters by comparing the responses to selection of P-M dysgenic and nondysgenic hybrids have given variable results. This experimental design has been extended to include an additional quantitative trait and the I-R hybrid dysgenesis system. The selection responses of lines founded from both dysgenic and nondysgenic crosses showed features that would be expected from the increase in frequency of initially rare genes with major effects on the selected traits. These results differ from those of previous experiments which showed additional selection response only in lines started from dysgenic crosses, and can be explained by the occasional occurrence of large effect transposable element-induced polygenic mutations in both dysgenic and nondysgenic selection lines. High rates of transposition in populations founded from nondysgenic crosses may account for the apparently contradictory results of the earlier selection experiments, and an explanation is proposed for its occurrence.

Animals↗
PubMed1989

Transposable elements and fitness in Drosophila melanogaster.

Transposable elements constitute a significant fraction of the Drosophila melanogaster genome. The five families of moderately repeated transposable elements identified to date occupy dispersed and variable genomic locations, but have relatively constant copy numbers per individual. What effect to these elements have on the fitness of the individuals harboring them? Experimental evidence relating to this question is reviewed. The relevant data fall into two broad categories. The first involves the determination of the distribution of transposable elements in natural populations, by restriction mapping or in situ hybridization, and the comparison of the observed distribution with different theoretical expectations. The second approach is to study directly the effects of new transposable element-induced mutations on fitness. The P family of transposable elements is a particularly efficient mutagen, and the results of experiments in which initially P-free chromosomes are contaminated with P elements are discussed with regard to P-induced fitness mutations.

Animals↗
PubMed1985

Transposable element-induced response to artificial selection in Drosophila melanogaster.

The P family of transposable elements in Drosophila melanogaster transpose with exceptionally high frequency when males from P strains carrying multiple copies of these elements are crossed to females from M strains that lack P elements, but with substantially lower frequency in the reciprocal cross. Transposition is associated with enhanced mutation rates, caused by insertion and deletion of P elements, and chromosome rearrangements. If P element mutagenesis creates additional variation for quantitative traits, accelerated response to artificial selection of progeny of M female female X P male male strain crosses is expected, compared with that from progeny of P female female X M male male strain crosses.--Divergent artificial selection for number of bristles on the last abdominal tergite was carried out for 16 generations among the progeny of P-strain males (Harwich) and M-strain females (Canton-S) and also of M-strain males (Canton-S) and P-strain females (Harwich). Each cross was replicated four times. Average realized heritability of abdominal bristle score for the crosses in which P transposition was expected was 0.244 +/- 0.017, 1.5 times greater than average heritability estimated from crosses in which transposition was expected to be rare (0.163 +/- 0.010). Phenotypic variance of abdominal bristle score increased by a factor of four in lines selected from M female female X P male male crosses when compared with those selected from P female female X M male male hybrids. Not all quantitative genetic variation induced by P elements is additive. A substantial fraction of nonadditive genetic variation is implicated by chromosomal analysis, which demonstrates deleterious fitness effects of the mutations when homozygous.--Several putative "quantitative" mutations were identified from chromosomes extracted from the selected lines; these will form the basis for further investigation at the molecular level of the genes controlling quantitative inheritance.

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