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C H Langley

Publications and source records attributed to C H Langley.

At least 19 recordsLinked to original sources
PubMed1992

Patterns of naturally occurring restriction map variation, dopa decarboxylase activity variation and linkage disequilibrium in the Ddc gene region of Drosophila melanogaster.

Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (greater than or equal to 9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show normal adult DDC activities.

Animals↗
PubMed1992

Evolutionary consequences of DNA mismatch inhibited repair opportunity.

Double strand breaks (DSBs) are often repaired via homologous recombination. Recombinational repair processes are expected to be influenced by nucleotide heterozygosity through mismatch detection systems. Unrepaired DSBs have severe biological consequences and are often lethal. We show that natural selection due to inhibition of recombinational repair associated with polymorphisms could influence their molecular evolution. The main conclusions from this analysis are that, for increasing population size, mismatch detection leads to a limit on average heterozygosity of otherwise selectively neutral polymorphism, an excess of rare variants, and a slowing down of the rate of neutral molecular evolution. The first two results suggest that mismatch detection may account for the surprisingly narrow range of observed average heterozygosities, given the great variation in population size between species.

Animals↗
PubMed1992

Polymorphism and divergence in the Mst26A male accessory gland gene region in Drosophila.

Drosophila males, like males of most other insects, transfer a group of specific proteins to the females during mating. These proteins are produced primarily in the accessory gland and are likely to influence the female's reproduction. The results of studies of DNA sequence polymorphism and divergence in two genes coding for male accessory gland proteins of Drosophila are reported here. The Mst26Aa and Mst26Ab transcription units are tandemly arranged in a approximately 1.6-kb segment in Drosophila sechellia, Drosophila mauritiana and Drosophila simulans as they were reported to be in Drosophila melanogaster. The DNA sequences of 10 alleles from D. melanogaster and one allele each from the three sibling species reveals a high degree of amino acid replacement variation. A substantial part of the variation is due to insertion/deletion differences. Possible functional significance of these amino acid sequence changes is discussed. Statistical analyses based on the neutral theory of molecular evolution show that the distribution of polymorphism over the 1.6-kb region is inconsistent with the pattern of divergence between the species. The amount of 4-cutter restriction map polymorphism in a larger sample of 75 alleles from the same D. melanogaster population is similar to that obtained from the DNA sequence of the 10 alleles (a pairwise average of 0.007 difference per site). The 6-cutter restriction map survey of a 18-kb region containing the Mst26A genes indicates that polymorphism in the region flanking these genes maybe higher. The failure of polymorphisms and divergence in the Mst26A region to conform to the expectations of a simple mutation-drift-equilibrium model indicates that selection in or near this region has played a role in the history of these genes.

Amino Acid Sequence↗
PubMed1991

Chromosome rearrangement by ectopic recombination in Drosophila melanogaster: genome structure and evolution.

Ectopic recombination between interspersed repeat sequences generates chromosomal rearrangements that have a major impact on genome structure. A survey of ectopic recombination in the region flanking the white locus of Drosophila melanogaster identified 25 transposon-mediated rearrangements from four parallel experiments. Eighteen of the 25 were generated from females carrying X chromosomes heterozygous for interspersed repeat sequences. The cytogenetic and molecular analyses of the rearrangements and the parental chromosomes show: (1) interchromosomal and intrachromosomal recombinants are generated in about equal numbers; (2) ectopic recombination appears to be a meiotic process that is stimulated by the interchromosomal effect to about the same degree as regular crossing over; (3) copies of the retrotransposon roo were involved in all of the interchromosomal exchanges; some copies were involved much more frequently than others in the target region; (4) homozygosis for interspersed repeat sequences and other sequence variations significantly reduced ectopic recombination.

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

Increased variation in ADH enzyme activity in Drosophila mutation-accumulation experiment is not due to transposable elements at the Adh structural gene.

We present here a molecular analysis of the region surrounding the structural gene encoding alcohol dehydrogenase (Adh) in 47 lines of Drosophila melanogaster that have each accumulated mutations for 300 generations. While these lines show a significant increase in variation of alcohol dehydrogenase enzyme activity compared to control lines, we found no restriction map variation in a 13-kb region including the complete Adh structural gene and roughly 5 kb of both 5' and 3' sequences. Thus, the rapid accumulation of ADH activity variation after 28,200 allele generations does not appear to have been due to the mobilization of transposable elements into or out of the Adh structural gene region.

Alcohol Dehydrogenase↗
PubMed1990

Molecular evolution of Drosophila metallothionein genes.

The metallothionein genes of Drosophila melanogaster, Mtn and Mto, may play an important role in heavy metal detoxification. Several different tandem duplications of Mtn have been shown to increase cadmium and copper tolerance, as well as Mtn expression. In order to investigate the possibility of increased selection for duplications of these genes in natural populations exposed to high levels of heavy metals, we compared the frequencies of such duplications among flies collected from metal-contaminated and non-contaminated orchards in Pennsylvania, Tennessee and Georgia. Restriction enzyme analysis was used to screen 1666 wild third chromosomes for Mtn duplications and a subset (327) of these lines for Mto duplications. The frequency of pooled Mtn duplications found ranged from 0% to 20%, and was not significantly higher at the contaminated sites. No Mto duplications were identified. Estimates of sequence diversity at the Mtn locus among a subsample (92) of the duplication survey were obtained using four-cutter analysis. This analysis revealed a low level of polymorphism, consistent with both selection at the Mtn locus, and a fairly recent origin for the duplications. To further examine this hypothesis, we sequenced an Mtn allele of Drosophila simulans and measured the amount of nucleotide sequence divergence between D. simulans and its sibling species D. melanogaster. The levels of silent nucleotide polymorphism and divergence in the Mtn region were compared with those in the Adh region, using the neutrality test of R.R. Hudson, M. Kreitman and M. Aguadé.

Alleles↗
PubMed1989

Restriction map and alpha-amylase activity variation among Drosophila mutation accumulation lines.

The specific activities of alpha-amylase were measured for two sets of mutation accumulation lines, each set having originated from a different lethal-carrying second chromosome and SM1(Cy) chromosome and having been maintained by a balanced lethal system for about 300 generations. Significant variation was found to have accumulated among lines of both sets. Because of dysgenic crosses in the early generations of mutation accumulation, insertions or deletions of transposable elements in the Amy gene region were suspected of being the cause of this variation. In order to test this possibility, the structural changes in the 14 kb region of these chromosomes that includes the structural genes for alpha-amylase were investigated by restriction map analysis. We found that most part of the activity variation is due to replacements of a chromosomal region of SM1(Cy), including the structural genes for alpha-amylase, by the corresponding regions of the lethal chromosomes. One line also contained an insertion in this region but this line has an intermediate activity value. Thus, insertions of transposable elements into the Amy gene region were not found to be responsible for the new variation observed in alpha-amylase activity. If we remove those lines with structural changes from the analysis, the genetic variance of alpha-amylase specific activity among lines becomes non-significant in both sets of chromosomes.

Animals↗
PubMed1989

Molecular genetic variation in the centromeric region of the X chromosome in three Drosophila ananassae populations. I. Contrasts between the vermilion and forked loci.

We have surveyed three natural populations of Drosophila ananassae for restriction map variation at the forked (f) and vermilion (v) loci, using 6-cutter restriction enzymes. Both loci are located in the centromeric region of the X chromosome. Two major conclusions can be drawn from the data. First, we found strong evidence for population subdivision, i.e., significant differences in the frequency distributions of polymorphisms and/or haplotypes between the Burma, India, and Brazil populations. Secondly, the pattern of DNA sequence variation between the two loci is unexpectedly different. The level of nucleotide variation in the v locus region is reduced (relative to f), especially in the Burma population. Furthermore, in contrast to v, we found no insertions/deletions larger than 700 bp and no significant linkage disequilibrium at f. The genetic differentiation among subpopulations can readily be attributed to restricted migration as the predominant evolutionary force. According to population genetics theory, the differences in DNA polymorphisms between the two loci are in qualitative agreement with the hypothesis that recombination is reduced in the v locus region ("centromere effect") but not at f. In order to test this hypothesis directly, we determined the cytogenetic positions of several loci in the centromeric region by in situ hybridization and found by comparison with the genetic map that recombination at v is indeed very low, much lower than at f.

Animals↗
PubMed1989

Analysis of the Om(1D) locus in Drosophila ananassae.

From the ca;px stock, which is the progenitor of Om mutants caused by insertions of the tom retrotransposon, 50 kb of genomic DNA including the Om(1D) locus was cloned by tom tagging and chromosome walking. Southern blot analyses of six Om(1D) mutants exposed one or two tom elements inserted at five nonrandom sites within an 18-kb distal segment of the restriction map; the phenotypic uniformity between these mutants was not affected by variations in the position, number or orientation of their inserts. Spontaneous revertants or more extreme derivatives of Om(1D) alleles were nonlinearly associated with losses or gains of tom inserts. Seven of eight radiation induced derivatives of Om(1D) mutants had one breakpoint of a chromosome rearrangement in polytene section 13A which includes the Om(1D) locus. Two Om(1D) derivatives, a spontaneous revertant and an induced extreme allele, were associated with overlapping deficiencies which define a region that is likely to contain the Om(1D) coding seguences proximal to the tom insertion sites. Incidental results confirm the previously indicated homology of the Om(1D) locus with the Bar locus of Drosophila melanogaster.

Animals↗
PubMed1989

The "hitchhiking effect" revisited.

The number of selectively neutral polymorphic sites in a random sample of genes can be affected by ancestral selectively favored substitutions at linked loci. The degree to which this happens depends on when in the history of the sample the selected substitutions happen, the strength of selection and the amount of crossing over between the sampled locus and the loci at which the selected substitutions occur. This phenomenon is commonly called hitchhiking. Using the coalescent process for a random sample of genes from a selectively neutral locus that is linked to a locus at which selection is taking place, a stochastic, finite population model is developed that describes the steady state effect of hitchhiking on the distribution of the number of selectively neutral polymorphic sites in a random sample. A prediction of the model is that, in regions of low crossing over, strongly selected substitutions in the history of the sample can substantially reduce the number of polymorphic sites in a random sample of genes from that expected under a neutral model.

Base Sequence↗
PubMed1989

Restriction-map variation at the zeste-tko region in natural populations of Drosophila melanogaster.

Restriction-map variation in 64 X chromosome lines extracted from three different natural populations of Drosophila melanogaster was investigated with seven six-nucleotide-recognizing enzymes for a 20-kb region including the zeste and tko genes. Ten restriction-site and four length polymorphisms (two insertions and two deletions) were detected. Contrary to the predicted lower level of variation for genes on the X chromosome, the level of variation attributable to nucleotide substitution (estimated heterozygosity/nucleotide = 0.004) was similar to that previously reported for autosomal loci. The amount of insertion/deletion variation in the studied region was within the range observed in autosomal regions and thus not explainable by a simple selection model against the effects of insertional mutations. A general lack of linkage disequilibrium between polymorphic sites was observed.

Animals↗
PubMed1988

Retrovirus-like features and site specific insertions of a transposable element, tom, in Drosophila ananassae.

The tom element, putatively associated with optic morphology (Om) mutations in Drosophila ananassae, was identified as a retrovirus-like transposable element. The tom element was found to terminate with 475 (or 474) base pair direct repeats which are identical in sequence to each other. Southern blot and heteroduplex analyses showed the tom element to have high homology to 297 and 17.6, two retrotransposons found in D. melanogaster. As in the cases of 297 and 17.6, tom includes nucleotide sequences coding for a presumptive protease and reverse transcriptase, similar in amino acid sequence to those of the Moloney murine leukaemia virus. At the tom insertion site of the sn9g locus, a host DNA sequence (T)ATAT was found to be duplicated on each side of the tom insertion and all other tom elements examined were also flanked by (T)ATAT. In each of six cases, the 5' flanking host sequence was TATAT. These results indicate that the target sequence of the tom element may be TATAT and that the entire region or a part of this sequence was duplicated on insertion of the tom element.

Animals↗
PubMed1988

Molecular and phenotypic variation of the white locus region in Drosophila melanogaster.

Restriction site and insertion/deletion polymorphism in a 45-kb region of the white locus on the X chromosome in Drosophila melanogaster was investigated for 64 X chromosome lines with six 6-cutter and ten 4-cutter restriction enzymes. A total of 109 polymorphisms were detected (54 restriction sites and 55 insertions/deletions). Estimated heterozygosity per nucleotide for this region (0.004-0.008) was similar to those of the Adh and 87A heat-shock locus regions located on the autosomes in D. melanogaster. This is contrary to a simple prediction based on the theory of mutation selection-balance of partially recessive deleterious mutants which predicts less variation on X chromosomes. Large linkage disequilibria between pairs of polymorphisms (including insertions and deletions) within the transcriptional unit (especially the 3' end of the 1st intron) were observed. As expected from population genetics theory, linkage disequilibria between these polymorphisms were greater for those pairs that are physically closer on the restriction map. Linkage equilibrium was typically observed when the pairs of sites were separated by 2 kb or more. Although significant between-line variation in eye pigment was observed (P less than 0.05), there is little evidence for strong associations between this phenotype and the polymorphisms at the DNA level.

Animals↗
PubMed1988

Restriction-map variation in the Notch region of Drosophila melanogaster.

A worldwide sample of 37 X chromosomes of Drosophila melanogaster was analyzed with four restriction endonucleases for a 60-kb region of the Notch locus. Any two randomly chosen homologous chromosomes were heterozygous at one in 143 nucleotides (theta = 0.007). The chromosomes that were sampled contained no more than one insertion/deletion. The four insertions and one deletion observed in the 37 chromosomes sampled were located 3' to the Notch transcript; one insertion was represented twice in the sample. The amount of linkage disequilibrium in the Notch region appears to be lower than that of the alcohol dehydrogenase locus in D. melanogaster. The few instances of linkage disequilibrium observed could be due to geographic differentiation of African populations. The genetic variation estimates in the Notch region were comparable with those of the alcohol dehydrogenase region in D. melanogaster, suggesting that molecular genetic variation on the X chromosome is not dramatically reduced by selection against slightly deleterious alleles.

Animals↗