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

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

Stephen W. Schaeffer^a,b, C. Scott Walthour^a, Donna M. Toleno^a, Anna T. Olek^a, and Ellen L. Miller^a
^a Department of Biology, The Pennsylvania State University, University Park, Pennsylvania 16802
^b Institute of Molecular Evolutionary Genetics, The Pennsylvania State University, University Park, Pennsylvania 16802

Corresponding author: Stephen W. Schaeffer, Department of Biology, The Pennsylvania State University, 208 Mueller Labs, University Park, PA 16802-5301., sws4{at}psu.edu (E-mail)

Communicating editor: G. B. GOLDING

A 3.5-kb segment of the alcohol dehydrogenase (Adh) region thatincludes the Adh and Adh-related genes was sequenced in 139Drosophila pseudoobscura strains collected from 13 populations.The Adh gene encodes four protein alleles and rejects a neutralmodel of protein evolution with the McDonald-Kreitman test,although the number of segregating synonymous sites is too highto conclude that adaptive selection has operated. The Adh-relatedgene encodes 18 protein haplotypes and fails to reject an equilibriumneutral model. The populations fail to show significant geographicdifferentiation of the Adh-related haplotypes. Eight of 404single nucleotide polymorphisms (SNPs) in the Adh region werein significant linkage disequilibrium with three ADHR proteinalleles. Coalescent simulations with and without recombinationwere used to derive the expected levels of significant linkagedisequilibrium between SNPs and 18 protein haplotypes. Maximumlevels of linkage disequilibrium are expected for protein allelesat moderate frequencies. In coalescent models without recombination,linkage disequilibrium decays between SNPs and high frequencyhaplotypes because common alleles mutate to haplotypes thatare rare or that reach moderate frequency. The implication ofthis study is that linkage disequilibrium mapping has the highestprobability of success with disease-causing alleles at frequenciesof 10%.

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