scholarly journals Molecular Evolution of Two Linked Genes, Est-6 and Sod, in Drosophila melanogaster

Genetics ◽  
1999 ◽  
Vol 153 (3) ◽  
pp. 1357-1369 ◽  
Author(s):  
Evgeniy S Balakirev ◽  
Elena I Balakirev ◽  
Francisco Rodríguez-Trelles ◽  
Francisco J Ayala
Keyword(s):  
Drosophila Melanogaster ◽  
Linkage Disequilibrium ◽  
Early Experiment ◽  
Amino Acid Replacement ◽  
Allozyme Polymorphism ◽  
Nucleotide Polymorphism ◽  
Significant Linkage Disequilibrium ◽  
Nucleotide Level ◽  
S Alleles ◽  
Significant Linkage

Abstract We have obtained 15 sequences of Est-6 from a natural population of Drosophila melanogaster to test whether linkage disequilibrium exists between Est-6 and the closely linked Sod, and whether natural selection may be involved. An early experiment with allozymes had shown linkage disequilibrium between these two loci, while none was detected between other gene pairs. The Sod sequences for the same 15 haplotypes were obtained previously. The two genes exhibit similar levels of nucleotide polymorphism, but the patterns are different. In Est-6, there are nine amino acid replacement polymorphisms, one of which accounts for the S-F allozyme polymorphism. In Sod, there is only one replacement polymorphism, which corresponds to the S-F allozyme polymorphism. The transversion/transition ratio is more than five times larger in Sod than in Est-6. At the nucleotide level, the S and F alleles of Est-6 make up two allele families that are quite different from each other, while there is relatively little variation within each of them. There are also two families of alleles in Sod, one consisting of a subset of F alleles, and the other consisting of another subset of F alleles, designed F(A), plus all the S alleles. The Sod F(A) and S alleles are completely or nearly identical in nucleotide sequence, except for the replacement mutation that accounts for the allozyme difference. The two allele families have independent evolutionary histories in the two genes. There are traces of statistically significant linkage disequilibrium between the two genes that, we suggest, may have arisen as a consequence of selection favoring one particular sequence at each locus.

scholarly journals Linkage disequilibrium in the white locus region of Drosophila melanogaster

1993 ◽  
Vol 62 (2) ◽  
pp. 101-109 ◽  
Author(s):  
Naohiko T. Miyashita ◽  
Montserrat Aguadé ◽  
Charles H. Langley
Keyword(s):  
Drosophila Melanogaster ◽  
Linkage Disequilibrium ◽  
Natural Populations ◽  
Restriction Enzymes ◽  
Transcriptional Unit ◽  
Similar Degree ◽  
Significant Linkage Disequilibrium ◽  
White Locus ◽  
Different Populations ◽  
Significant Linkage

SummaryLinkage disequilibrium between molecular polymorphisms in a 10 kb region in the white locus of Drosophila melanogaster, revealed with a battery of four-cutter restriction enzymes, was investigated in 266 lines sampled from seven natural populations around the world. A total of 73 (35 restriction site, 37 insertion/deletion and 1 inversion) polymorphisms were detected, of which 55 non-unique polymorphisms were analysed for linkage disequilibrium. Clustering of significant linkage disequilibrium was observed in the transcriptional unit of the white locus as in Miyashita & Langley (1988). It was shown that about two thirds of the 2-locus combinations showing significant linkage disequilibrium have similar degree and direction of association over different populations. Despite lower divergence in allelic frequencies of molecular polymorphisms among populations, an increase in the proportion of 2-locus pairs showing significant linkage disequilibrium is observed in the transcriptional unit. Large values of Ohta's D measure ratio (1982 a, b) cluster in the transcriptional unit, and correspond to significant linkage disequilibria. Although the exact molecular mechanism is not clear, these results suggest that epistatic selection is responsible for significant linkage disequilibrium in the transcriptional unit of this locus

Protein Variation in ADH and ADH-RELATED in Drosophila pseudoobscura: Linkage Disequilibrium Between Single Nucleotide Polymorphisms and Protein Alleles

Genetics ◽  
2001 ◽  
Vol 159 (2) ◽  
pp. 673-687
Author(s):  
Stephen W Schaeffer ◽  
C Scott Walthour ◽  
Donna M Toleno ◽  
Anna T Olek ◽  
Ellen L Miller
Keyword(s):  
Linkage Disequilibrium ◽  
Single Nucleotide Polymorphisms ◽  
Drosophila Pseudoobscura ◽  
Linkage Disequilibrium Mapping ◽  
Nucleotide Polymorphisms ◽  
Neutral Model ◽  
Significant Linkage Disequilibrium ◽  
Single Nucleotide ◽  
Synonymous Sites ◽  
Significant Linkage

Abstract A 3.5-kb segment of the alcohol dehydrogenase (Adh) region that includes the Adh and Adh-related genes was sequenced in 139 Drosophila pseudoobscura strains collected from 13 populations. The Adh gene encodes four protein alleles and rejects a neutral model of protein evolution with the McDonald-Kreitman test, although the number of segregating synonymous sites is too high to conclude that adaptive selection has operated. The Adh-related gene encodes 18 protein haplotypes and fails to reject an equilibrium neutral model. The populations fail to show significant geographic differentiation of the Adh-related haplotypes. Eight of 404 single nucleotide polymorphisms (SNPs) in the Adh region were in significant linkage disequilibrium with three ADHR protein alleles. Coalescent simulations with and without recombination were used to derive the expected levels of significant linkage disequilibrium between SNPs and 18 protein haplotypes. Maximum levels of linkage disequilibrium are expected for protein alleles at moderate frequencies. In coalescent models without recombination, linkage disequilibrium decays between SNPs and high frequency haplotypes because common alleles mutate to haplotypes that are rare or that reach moderate frequency. The implication of this study is that linkage disequilibrium mapping has the highest probability of success with disease-causing alleles at frequencies of 10%.

Estimates of linkage disequilibrium and the recombination parameter determined from segregating nucleotide sites in the alcohol dehydrogenase region of Drosophila pseudoobscura.

Genetics ◽  
1993 ◽  
Vol 135 (2) ◽  
pp. 541-552 ◽  
Author(s):  
S W Schaeffer ◽  
E L Miller
Keyword(s):  
Linkage Disequilibrium ◽  
Alcohol Dehydrogenase ◽  
Distance Effect ◽  
Theoretical Distribution ◽  
Drosophila Pseudoobscura ◽  
Significant Linkage Disequilibrium ◽  
Effective Population ◽  
Nucleotide Distance ◽  
Significant Linkage ◽  
Recombination Parameter

Abstract The alcohol dehydrogenase (Adh) region of Drosophila pseudoobscura, which includes the two genes Adh and Adh-Dup, was used to examine the pattern and organization of linkage disequilibrium among pairs of segregating nucleotide sites. A collection of 99 strains from the geographic range of D. pseudoobscura were nucleotide-sequenced with polymerase chain reaction-mediated techniques. All pairs of the 359 polymorphic sites in the 3.5-kb Adh region were tested for significant linkage disequilibrium with Fisher's exact test. Of the 74,278 pairwise comparisons of segregating sites, 127 were in significant linkage disequilibrium at the 5% level. The distribution of five linkage disequilibrium estimators D(ij), D2, r(ij), r2 and D(ij) were compared to theoretical distributions. The observed distributions of D(ij), D2, r(ij) and r2 were consistent with the theoretical distribution given an infinite sites model. The observed distribution of D(ij) differed from the theoretical distribution because of an excess of values at -1 and 1. No spatial pattern was observed in the linkage disequilibrium pattern in the Adh region except for two clusters of sites nonrandomly associated in the adult intron and intron 2 of Adh. The magnitude of linkage disequilibrium decreases significantly as nucleotide distance increases, or a distance effect. Adh-Dup had a larger estimate of the recombination parameter, 4Nc, than Adh, where N is the effective population size and c is the recombination rate. A comparison of the mutation and recombination parameters shows that 7-17 recombination events occur for each mutation event. The heterogeneous estimates of the recombination parameter and the inverse relationship between linkage disequilibrium and nucleotide distance are no longer significant when the two clusters of Adh intron sites are excluded from analyses. The most likely explanation for the two clusters of linkage disequilibria is epistatic selection between sites in the cluster to maintain pre-mRNA secondary structure.

scholarly journals Nucleotide Variation and Conservation at the dpp Locus, a Gene Controlling Early Development in Drosophila

Genetics ◽  
1997 ◽  
Vol 145 (2) ◽  
pp. 311-323 ◽  
Author(s):  
Brent Richter ◽  
Manyuan Long ◽  
R C Lewontin ◽  
Eiji Nitasaka
Keyword(s):  
Linkage Disequilibrium ◽  
Amino Acid ◽  
Gene Conversion ◽  
Haplotype Diversity ◽  
Amino Acid Replacement ◽  
Nucleotide Variation ◽  
Nucleotide Level ◽  
Untranslated Sequence ◽  
Gene Coding ◽  
Large Intron

A study of polymorphism and species divergence of the dpp gene of Drosophila has been made. Eighteen lines from a population of D. melanogaster were sequenced for 5200 bp of the Hin region of the gene, coding for the dpp polypeptide. A comparison was made with sequence from D. simulans. Ninety-six silent polymorphisms and three amino acid replacement polymorphisms were found. The overall silent polymorphism (0.0247) is low, but haplotype diversity (0.0066 for effectively silent sites and 0.0054 for all sites) is in the range found for enzyme loci. Amino acid variation is absent in the N-terminal signal peptide, the C-terminal TGF-β peptide and in the N-terminal half of the pro-protein region. At the nucleotide level there is strong conservation in the middle half of the large intron and in the 3′ untranslated sequence of the last exon. The 3′ untranslated conservation, which is perfect for 110 bp among all the divergent species, is unexplained. There is strong positive linkage disequilibrium among polymorphic sites, with stretches of apparent gene conversion among originally divergent sequences. The population apparently is a migration mixture of divergent clades.

scholarly journals Linkage disequilibrium in growing and stable populations.

Genetics ◽  
1994 ◽  
Vol 137 (1) ◽  
pp. 331-336 ◽  
Author(s):  
M Slatkin
Keyword(s):  
Linkage Disequilibrium ◽  
Sequence Data ◽  
Significant Linkage Disequilibrium ◽  
Rapid Population Growth ◽  
Exact Test ◽  
Dna Sequence Data ◽  
Constant Size ◽  
Significant Linkage ◽  
Stable Populations ◽  
Growing Population

Abstract Nonrandom associations between alleles at different loci can be tested for using Fisher's exact test. Extensive simulations show that there is a substantial probability of obtaining significant nonrandom associations between closely or completely linked polymorphic neutral loci in a population of constant size at equilibrium under mutation and genetic drift. In a rapidly growing population, however, there will be little chance of finding significant nonrandom associations even between completely linked loci if the growth has been sufficiently rapid. This result is illustrated by the analysis of mitochondrial DNA sequence data from humans. In comparing all pairs of informative sites, fewer than 5% of the pairs show significant disequilibrium in Sardinians, which have apparently undergone rapid population growth, while 20% to 30% in !Kung and Pygmies, which apparently have not undergone rapid growth, show significance. The extent of linkage disequilibrium in a population is closely related to the gene genealogies of the loci examined, with "star-like" genealogies making significant linkage disequilibrium unlikely.

scholarly journals Selective Sweep at the Drosophila melanogaster Suppressor of Hairless Locus and Its Association With the In(2L)t Inversion Polymorphism

Genetics ◽  
1999 ◽  
Vol 152 (3) ◽  
pp. 1017-1024 ◽  
Author(s):  
Frantz Depaulis ◽  
Lionel Brazier ◽  
Michel Veuille
Keyword(s):  
Drosophila Melanogaster ◽  
Selective Sweep ◽  
Chromosome Region ◽  
Haplotype Diversity ◽  
Nucleotide Polymorphisms ◽  
Significant Linkage Disequilibrium ◽  
Suppressor Of Hairless ◽  
Chromosome Sequence ◽  
Neutrality Tests ◽  
Significant Linkage

Abstract The hitchhiking model of population genetics predicts that an allele favored by Darwinian selection can replace haplotypes from the same locus previously established at a neutral mutation-drift equilibrium. This process, known as “selective sweep,” was studied by comparing molecular variation between the polymorphic In(2L)t inversion and the standard chromosome. Sequence variation was recorded at the Suppressor of Hairless (Su[H]) gene in an African population of Drosophila melanogaster. We found 47 nucleotide polymorphisms among 20 sequences of 1.2 kb. Neutrality tests were nonsignificant at the nucleotide level. However, these sites were strongly associated, because 290 out of 741 observed pairwise combinations between them were in significant linkage disequilibrium. We found only seven haplotypes, two occurring in the 9 In(2L)t chromosomes, and five in the 11 standard chromosomes, with no shared haplotype. Two haplotypes, one in each chromosome arrangement, made up two-thirds of the sample. This low haplotype diversity departed from neutrality in a haplotype test. This pattern supports a selective sweep hypothesis for the Su(H) chromosome region.

Contrasting Evolutionary Histories of Two Introns of the Duchenne Muscular Dystrophy Gene, Dmd, in Humans

Genetics ◽  
2000 ◽  
Vol 155 (4) ◽  
pp. 1855-1864 ◽  
Author(s):  
Michael W Nachman ◽  
Susan L Crowell
Keyword(s):  
Linkage Disequilibrium ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Nucleotide Diversity ◽  
High Rate ◽  
Significant Linkage Disequilibrium ◽  
Nucleotide Variability ◽  
Interspecific Divergence ◽  
Significant Linkage ◽  
Common Chimpanzee

Abstract The Duchenne muscular dystrophy (Dmd) locus lies in a region of the X chromosome that experiences a high rate of recombination and is thus expected to be relatively unaffected by the effects of selection on nearby genes. To provide a picture of nucleotide variability at a high-recombination locus in humans, we sequenced 5.4 kb from two introns of Dmd in a worldwide sample of 41 alleles from Africa, Asia, Europe, and the Americas. These same regions were also sequenced in one common chimpanzee and one orangutan. Dramatically different patterns of genetic variation were observed at these two introns, which are separated by >500 kb of DNA. Nucleotide diversity at intron 44 (π = 0.141%) was more than four times higher than nucleotide diversity at intron 7 (π = 0.034%) despite similar levels of divergence for these two regions. Intron 7 exhibited significant linkage disequilibrium extending over 10 kb and also showed a significant excess of rare polymorphisms. In contrast, intron 44 exhibited little linkage disequilibrium and no skew in the frequency distribution of segregating sites. Intron 7 was much more variable in Africa than in other continents, while intron 44 displayed similar levels of variability in different geographic regions. Comparison of intraspecific polymorphism to interspecific divergence using the HKA test revealed a significant reduction in variability at intron 7 relative to intron 44, and this effect was most pronounced in the non-African samples. These results are best explained by positive directional selection acting at or near intron 7 and demonstrate that even genes in regions of high recombination may be influenced by selection at linked sites.

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