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. 2006 May 9;16(9):912-9.
doi: 10.1016/j.cub.2006.03.051.

Phenotypic variation and natural selection at catsup, a pleiotropic quantitative trait gene in Drosophila

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Phenotypic variation and natural selection at catsup, a pleiotropic quantitative trait gene in Drosophila

Mary Anna Carbone et al. Curr Biol. .

Abstract

Quantitative traits are shaped by networks of pleiotropic genes . To understand the mechanisms that maintain genetic variation for quantitative traits in natural populations and to predict responses to artificial and natural selection, we must evaluate pleiotropic effects of underlying quantitative trait genes and define functional allelic variation at the level of quantitative trait nucleotides (QTNs). Catecholamines up (Catsup), which encodes a negative regulator of tyrosine hydroxylase , the rate-limiting step in the synthesis of the neurotransmitter dopamine, is a pleiotropic quantitative trait gene in Drosophila melanogaster. We used association mapping to determine whether the same or different QTNs at Catsup are associated with naturally occurring variation in multiple quantitative traits. We sequenced 169 Catsup alleles from a single population and detected 33 polymorphisms with little linkage disequilibrium (LD). Different molecular polymorphisms in Catsup are independently associated with variation in longevity, locomotor behavior, and sensory bristle number. Most of these polymorphisms are potentially functional variants in protein coding regions, have large effects, and are not common. Thus, Catsup is a pleiotropic quantitative trait gene, but individual QTNs do not have pleiotropic effects. Molecular population genetic analyses of Catsup sequences are consistent with balancing selection maintaining multiple functional polymorphisms.

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Figures

Figure 1.
Figure 1.
Catsup Polymorphisms (A) The Catsup gene structure is depicted with the number and distribution of SNPs (circle) and InDels (triangle) in 169 Catsup alleles sampled from the Raleigh population. The promoter region is predicted and not functionally confirmed. LD in Catsup is shown below the gene structure, with p values from Fisher’s Exact Test above the diagonal and estimates of r2 below the diagonal. (B) Departures of LD in Catsup from the level expected given the maximum likelihood estimate of the population recombination parameter, 4Nr. Red and blue blocks depict pairwise associations that exhibit significantly less LD and significantly more LD, respectively, than expected.
Figure 2.
Figure 2.
Genotype-Phenotype Associations at Catsup (A) Plots of p values (transformed to log(1/P), y axis) from ANOVA tests of association of longevity (dark blue), locomotor behavior (purple), and starvation resistance (black) for each of the polymorphic markers at Catsup (x axis). (B) Plots of p values (transformed to log(1/P), y axis) from ANOVA tests of association of abdominal bristle number (yellow), environmental plasticity of abdominal bristle number (green), and sternopleural bristle number (teal) for each of the polymorphic markers at Catsup (x axis). In both (A) and (B), the red horizontal dashed line indicates the experiment-wise p < 0.05 threshold given by the Bonferroni correction for multiple tests, and the black horizontal dashed line indicates the nominal p < 0.05 significance threshold. (C) Predicted Catsup protein structure and locations of potentially functional amino acid polymorphisms associated with lifespan (dark blue), locomotor behavior (purple), abdominal bristle number (yellow), environmental plasticity in abdominal bristle number (teal), and sternopleural bristle number (light blue).
Figure 3.
Figure 3.
Sliding Window Analysis of the Ratio of Nonsynonymous to Synonymous Variation at Catsup The solid black line denotes πN/πS ratios and the gray line indicates DN/DS ratios (right y axis). The solid and broken red lines denote polymorphism (π) within D. melanogaster and divergence between D. melanogaster and D. simulans, respectively (left y axis). Windows were 100 bp with a step size of 10 bp. The gene structure of Catsup is indicated below the x axis. The scale is in bp, with 1 indicating the translation start site.

References

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